From a305364fa095b26cb39a77399070c4adfbfff1c1 Mon Sep 17 00:00:00 2001 From: Ben Deadman Date: Wed, 18 Dec 2024 17:01:13 +0000 Subject: [PATCH 1/7] Example of updating a dataset --- .../Granda_Perera_ml_example.ipynb | 2 +- .../example_Santanilla.ipynb | 2 +- .../updates/1_Golden/Fig_7_data_corrected.csv | 289 ++++++ ...set-a12fa15d036d489c971b0b514caeae52.pb.gz | Bin 0 -> 27096 bytes ...a12fa15d036d489c971b0b514caeae52_old.pb.gz | Bin 0 -> 24772 bytes .../updates/1_Golden/update-dataset.ipynb | 937 ++++++++++++++++++ 6 files changed, 1228 insertions(+), 2 deletions(-) create mode 100644 examples/updates/1_Golden/Fig_7_data_corrected.csv create mode 100644 examples/updates/1_Golden/ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz create mode 100644 examples/updates/1_Golden/ord_dataset-a12fa15d036d489c971b0b514caeae52_old.pb.gz create mode 100644 examples/updates/1_Golden/update-dataset.ipynb diff --git a/examples/applications/Perera_Science_Granda_Nature_Suzuki/Granda_Perera_ml_example.ipynb b/examples/applications/Perera_Science_Granda_Nature_Suzuki/Granda_Perera_ml_example.ipynb index e235f6411..bfd39050d 100644 --- a/examples/applications/Perera_Science_Granda_Nature_Suzuki/Granda_Perera_ml_example.ipynb +++ b/examples/applications/Perera_Science_Granda_Nature_Suzuki/Granda_Perera_ml_example.ipynb @@ -2503,7 +2503,7 @@ "name": "python", "nbconvert_exporter": "python", "pygments_lexer": "ipython3", - "version": "3.10.13" + "version": "3.11.7" } }, "nbformat": 4, diff --git a/examples/submissions/1_Santanilla_Nanomole_HTE/example_Santanilla.ipynb b/examples/submissions/1_Santanilla_Nanomole_HTE/example_Santanilla.ipynb index 0e1efc214..f42459b5c 100644 --- a/examples/submissions/1_Santanilla_Nanomole_HTE/example_Santanilla.ipynb +++ b/examples/submissions/1_Santanilla_Nanomole_HTE/example_Santanilla.ipynb @@ -7049,7 +7049,7 @@ "name": "python", "nbconvert_exporter": "python", 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This notebook details the workflow used to update the dataset whilst maintaining the dataset and reaction ids." + ] + }, + { + "cell_type": "code", + "execution_count": 1, + "id": "cbaf6dda-7b56-4110-8fd5-e1ab9bf7aeeb", + "metadata": {}, + "outputs": [], + "source": [ + "# Import modules\n", + "import ord_schema\n", + "from ord_schema import message_helpers, validations, updates\n", + "from ord_schema.proto import dataset_pb2\n", + "from ord_schema.proto import reaction_pb2\n", + "\n", + "import math\n", + "import pandas as pd\n", + "import numpy as np\n", + "import os\n", + "#import wget\n", + "from datetime import datetime\n", + "\n", + "from glob import glob" + ] + }, + { + "cell_type": "markdown", + "id": "e216da23-a415-4682-ac0d-0ba8b58faaa7", + "metadata": {}, + "source": [ + "## Load in the dataset to be updated" + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "id": "d4bbf6d1-01c1-4666-96f9-74938b3edb2a", + "metadata": {}, + "outputs": [], + "source": [ + "# Download the dataset\n", + "# on Linux\n", + "#url = \"https://github.com/open-reaction-database/ord-data/blob/main/data/a1/ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz\"\n", + "#pb = wget.download(url)\n", + "\n", + "# on Windows - manually download the dataset to a directory containing this notebook\n" + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "id": "b6ec3f23-76ec-4a3c-b163-e3258012ca36", + "metadata": {}, + "outputs": [], + "source": [ + "# Load the dataset to be updated\n", + "pb = './ord_dataset-a12fa15d036d489c971b0b514caeae52_old.pb.gz'\n", + "data = message_helpers.load_message(pb, dataset_pb2.Dataset)" + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "id": "a06370cf-8f8a-4a7b-8f7b-1d3830b9145b", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Dataset name is Fig 7 data from Golden paper\n", + "Dataset descripton is Cross-coupling of 3-(1-chloroethyl)pyridine with a range of  nucleophiles. Data from Fig 7 of https://doi.org/10.1016/j.chempr.2024.04.001.\n" + ] + } + ], + "source": [ + "# Inspect the dataset\n", + "print(f\"Dataset name is {data.name}\")\n", + "print(f\"Dataset descripton is {data.description}\")" + ] + }, + { + "cell_type": "code", + "execution_count": 5, + "id": "92178e6c-5a42-4a31-9d37-382f95895fe5", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "

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283H8Cc1ccccc1-n1ncc(C(=O)O)c1CCc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C81.0ord-19f1549ea6f44eae96973699b7e6d0a0
284H9O=C(O)c1cn(Cc2ccccc2)nn1CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc191.0ord-0133a2a17eb34832a8f573384e89d644
285H10O=C(O)c1nn(CC2CC2)c2ccccc12CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc171.0ord-c30c707842604783b1da44ea48737140
286H11O=C(O)c1ncn2c1CCCC2CC(OC(=O)c1ncn2c1CCCC2)c1cccnc196.0ord-79706a33f8734f4088c293968ee9782f
287H12C=CCOc1cn(-c2ccccc2)nc1C(=O)OC=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc165.0ord-550018100d194a0aadd041e992676da6
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288 rows × 5 columns

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" + ], + "text/plain": [ + " identifiers[1].value \\\n", + "0 A1 \n", + "1 A2 \n", + "2 A3 \n", + "3 A4 \n", + "4 A5 \n", + ".. ... \n", + "283 H8 \n", + "284 H9 \n", + "285 H10 \n", + "286 H11 \n", + "287 H12 \n", + "\n", + " inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value \\\n", + "0 NCCSCc1ccco1 \n", + "1 CC(C)(C)Oc1ccc(CCCN)cc1 \n", + "2 Cc1ccc(S(=O)(=O)CCN)cc1 \n", + "3 NCC1(N2CCCCC2)CCOCC1 \n", + "4 N[C@@H]1C[C@H]2CC[C@@H]1C2 \n", + ".. ... \n", + "283 Cc1ccccc1-n1ncc(C(=O)O)c1C \n", + "284 O=C(O)c1cn(Cc2ccccc2)nn1 \n", + "285 O=C(O)c1nn(CC2CC2)c2ccccc12 \n", + "286 O=C(O)c1ncn2c1CCCC2 \n", + "287 C=CCOc1cn(-c2ccccc2)nc1C(=O)O \n", + "\n", + " outcomes[0].products[0].identifiers[0].value \\\n", + "0 CC(NCCSCc1ccco1)c1cccnc1 \n", + "1 CC(NCCCc1ccc(OC(C)(C)C)cc1)c1cccnc1 \n", + "2 CC(N[C@H]1CCCC[C@@H]1OCc1ccccc1)c1cccnc1 \n", + "3 Cc1ccc(S(=O)(=O)CCNC(C)c2cccnc2)cc1 \n", + "4 CC(NCC1(N2CCCCC2)CCOCC1)c1cccnc1 \n", + ".. ... \n", + "283 Cc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C \n", + "284 CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc1 \n", + "285 CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc1 \n", + "286 CC(OC(=O)c1ncn2c1CCCC2)c1cccnc1 \n", + "287 C=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc1 \n", + "\n", + " outcomes[0].products[0].measurements[0].percentage.value \\\n", + "0 61.0 \n", + "1 67.0 \n", + "2 56.0 \n", + "3 63.0 \n", + "4 63.0 \n", + ".. ... \n", + "283 81.0 \n", + "284 91.0 \n", + "285 71.0 \n", + "286 96.0 \n", + "287 65.0 \n", + "\n", + " reaction_id \n", + "0 ord-eafdcf86ab4049bdaced8adc28ff4b42 \n", + "1 ord-ab68ccc98d184f9c82b51e02e72399eb \n", + "2 ord-85c8f00118eb4899b36ddc53112d676f \n", + "3 ord-0e5399b5617a489e98405c3172c8779d \n", + "4 ord-ed93dbd8dace4e078573612131d2ef2f \n", + ".. ... \n", + "283 ord-19f1549ea6f44eae96973699b7e6d0a0 \n", + "284 ord-0133a2a17eb34832a8f573384e89d644 \n", + "285 ord-c30c707842604783b1da44ea48737140 \n", + "286 ord-79706a33f8734f4088c293968ee9782f \n", + "287 ord-550018100d194a0aadd041e992676da6 \n", + "\n", + "[288 rows x 5 columns]" + ] + }, + "execution_count": 5, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# To find the messages which need updating it can be helpful to view the dataset as a DataFrame\n", + "# Convert dataset to pandas dataframe\n", + "df = message_helpers.messages_to_dataframe(data.reactions, drop_constant_columns=True)\n", + "\n", + "# View dataframe\n", + "df" + ] + }, + { + "cell_type": "markdown", + "id": "c56d83a4-9862-4df9-b79b-529549e3e2c1", + "metadata": {}, + "source": [ + "### Notes\n", + "The column names can help identify the messages which may be updated." + ] + }, + { + "cell_type": "markdown", + "id": "e91e78eb-aefc-48ef-b768-6bbc87aef99e", + "metadata": {}, + "source": [ + "## Load in the new source data" + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "id": "feb7e488-b983-4278-a509-581a7b281f2b", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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Wellnucleophile_smilesproduct_smilesLCAP
0A1NCCSCC1=CC=CO1CC(C1=CC=CN=C1)NCCSCC2=CC=CO261
1A2NCCCC2=CC=C(C=C2)OC(C)(C)CCC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C67
2A3NCCS(=O)(C3=CC=C(C)C=C3)=OO=S(CCNC(C)C5=CC=CN=C5)(C6=CC=C(C)C=C6)=O56
3A4NCC4(CCOCC4)N5CCCCC5CC(C7=CC=CN=C7)NCC8(CCOCC8)N9CCCCC963
4A5N[C@@H]6C[C@H]7CC[C@@H]6C7CC(C%10=CC=CN=C%10)N[C@@H]%11C[C@H]%12CC[C@@H]...63
...............
283H8Cc1ccccc1-n1ncc(C(=O)O)c1CCc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C81
284H9O=C(O)c1cn(Cc2ccccc2)nn1CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc191
285H10O=C(O)c1nn(CC2CC2)c2ccccc12CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc171
286H11O=C(O)c1ncn2c1CCCC2CC(OC(=O)c1ncn2c1CCCC2)c1cccnc196
287H12C=CCOc1cn(-c2ccccc2)nc1C(=O)OC=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc165
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288 rows × 4 columns

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" + ], + "text/plain": [ + " Well nucleophile_smiles \\\n", + "0 A1 NCCSCC1=CC=CO1 \n", + "1 A2 NCCCC2=CC=C(C=C2)OC(C)(C)C \n", + "2 A3 NCCS(=O)(C3=CC=C(C)C=C3)=O \n", + "3 A4 NCC4(CCOCC4)N5CCCCC5 \n", + "4 A5 N[C@@H]6C[C@H]7CC[C@@H]6C7 \n", + ".. ... ... \n", + "283 H8 Cc1ccccc1-n1ncc(C(=O)O)c1C \n", + "284 H9 O=C(O)c1cn(Cc2ccccc2)nn1 \n", + "285 H10 O=C(O)c1nn(CC2CC2)c2ccccc12 \n", + "286 H11 O=C(O)c1ncn2c1CCCC2 \n", + "287 H12 C=CCOc1cn(-c2ccccc2)nc1C(=O)O \n", + "\n", + " product_smiles LCAP \n", + "0 CC(C1=CC=CN=C1)NCCSCC2=CC=CO2 61 \n", + "1 CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C 67 \n", + "2 O=S(CCNC(C)C5=CC=CN=C5)(C6=CC=C(C)C=C6)=O 56 \n", + "3 CC(C7=CC=CN=C7)NCC8(CCOCC8)N9CCCCC9 63 \n", + "4 CC(C%10=CC=CN=C%10)N[C@@H]%11C[C@H]%12CC[C@@H]... 63 \n", + ".. ... ... \n", + "283 Cc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C 81 \n", + "284 CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc1 91 \n", + "285 CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc1 71 \n", + "286 CC(OC(=O)c1ncn2c1CCCC2)c1cccnc1 96 \n", + "287 C=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc1 65 \n", + "\n", + "[288 rows x 4 columns]" + ] + }, + "execution_count": 6, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Load in the replacement data\n", + "path = './Fig_7_data_corrected.csv'\n", + "df_replace = pd.read_csv(path)\n", + "df_replace" + ] + }, + { + "cell_type": "markdown", + "id": "60c3f3c4-ef7b-4e99-8779-33ee8774583c", + "metadata": {}, + "source": [ + "### Notes\n", + "We know that some, but not all, of the nucleophile_smiles and product_smiles have been corrected. Well, and LCAP are unchanged." + ] + }, + { + "cell_type": "markdown", + "id": "d521de12-72a5-4ec2-9077-4478dc440234", + "metadata": {}, + "source": [ + "## Update the dataset" + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "id": "048d5f5b-a98e-4dcc-9b3d-852e7ce492bd", + "metadata": {}, + "outputs": [], + "source": [ + "# Make a new copy of the dataset for updating\n", + "data2 = message_helpers.load_message(pb, dataset_pb2.Dataset)" + ] + }, + { + "cell_type": "code", + "execution_count": 9, + "id": "4165bf4c-5408-4ef8-87b9-f170df702673", + "metadata": {}, + "outputs": [], + "source": [ + "# Iterate over the dataset and update reactions\n", + "for index, row in df_replace.iterrows():\n", + " # check if the reaction needs to be updated\n", + " if data.reactions[index].inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value != row['nucleophile_smiles'] or \\\n", + " data.reactions[index].outcomes[0].products[0].identifiers[0].value != row['product_smiles']:\n", + "\n", + " data2.reactions[index].inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value = row['nucleophile_smiles']\n", + " data2.reactions[index].outcomes[0].products[0].identifiers[0].value = row['product_smiles']\n", + " # Add a record_modified event.\n", + " event = data2.reactions[index].provenance.record_modified.add()\n", + " event.time.value = datetime.now().strftime(\"%m/%d/%Y, %H:%M:%S\")\n", + " event.person.CopyFrom(\n", + " reaction_pb2.Person(\n", + " name=\"Benjamin J. Deadman\", organization=\"Open Reaction Database\", orcid=\"0000-0001-8463-8199\", email=\"ben@bjdeadman.co.uk\"\n", + " )\n", + " )\n", + " event.details = \"Corrected the reactant and product SMILES strings\"\n", + " #print(f\"reaction {index} was updated\")\n", + " \n", + " else: \n", + " #print(f\"reaction {index} is unchaged\")\n", + " pass" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "id": "04b6cab5-d7f8-48c6-b70c-a4c3cbb61438", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "type: SMILES\n", + "value: \"NCCCC2=CC=C(C=C2)OC(C)(C)C\"\n", + "\n", + "type: SMILES\n", + "value: \"CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C\"\n", + "\n", + "doi: \"10.1016/j.chempr.2024.04.001\"\n", + "publication_url: \"https://doi.org/10.1016/j.chempr.2024.04.001\"\n", + "record_created {\n", + " time {\n", + " value: \"7/24/2024, 3:36:42 PM\"\n", + " }\n", + " person {\n", + " name: \"Spencer P. Heins\"\n", + " organization: \"UW-Madison\"\n", + " email: \"sheins@wisc.edu\"\n", + " }\n", + "}\n", + "record_modified {\n", + " time {\n", + " value: \"Wed Jul 31 22:03:49 2024\"\n", + " }\n", + " person {\n", + " username: \"github-actions\"\n", + " email: \"github-actions@github.com\"\n", + " }\n", + " details: \"Automatic updates from the submission pipeline.\"\n", + "}\n", + "record_modified {\n", + " time {\n", + " value: \"12/18/2024, 16:17:40\"\n", + " }\n", + " person {\n", + " name: \"Benjamin J. Deadman\"\n", + " orcid: \"0000-0001-8463-8199\"\n", + " organization: \"Open Reaction Database\"\n", + " email: \"ben@bjdeadman.co.uk\"\n", + " }\n", + " details: \"Corrected the reactant and product SMILES strings\"\n", + "}\n", + "\n" + ] + } + ], + "source": [ + "# Inspect a single reaction to view the updated fields in the reaction record\n", + "r_index = 1 # check the reaction at this index\n", + "print(data2.reactions[r_index].inputs[\"Nucleophile in DMF\"].components[0].identifiers[0])\n", + "print(data2.reactions[r_index].outcomes[0].products[0].identifiers[0])\n", + "print(data2.reactions[r_index].provenance)" + ] + }, + { + "cell_type": "markdown", + "id": "73497bf4-4664-4b30-aaed-4f8983393b46", + "metadata": {}, + "source": [ + "## Comparing the datasets" + ] + }, + { + "cell_type": "code", + "execution_count": 14, + "id": "daf8ff8d-4aaf-4748-9ef7-5ec73f2d8d23", + "metadata": {}, + "outputs": [], + "source": [ + "# Convert the datasets to DataFrames, and keep constant columns so that we can see any added messages\n", + "df1 = message_helpers.messages_to_dataframe(data.reactions, drop_constant_columns=False)\n", + "df2 = message_helpers.messages_to_dataframe(data2.reactions, drop_constant_columns=False)" + ] + }, + { + "cell_type": "code", + "execution_count": 18, + "id": "cd9fb8dd-d0cb-48a2-8e27-c2fb9d7a91c2", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "(288, 127)\n", + "(288, 133)\n" + ] + } + ], + "source": [ + "# Compare the shape of the DataFrames to confirm that the updated df2 has additional columns for the record_modified metadata\n", + "print(df1.shape)\n", + "print(df2.shape)" + ] + }, + { + "cell_type": "code", + "execution_count": 26, + "id": "c123f794-e164-433f-a7cf-c1bfa908cf20", + "metadata": {}, + "outputs": [], + "source": [ + "# Convert the datasets to compact DataFrames\n", + "df1b = message_helpers.messages_to_dataframe(data.reactions, drop_constant_columns=True)\n", + "df2b = message_helpers.messages_to_dataframe(data2.reactions, drop_constant_columns=True)" + ] + }, + { + "cell_type": "code", + "execution_count": 28, + "id": "b38cedb5-9894-49ae-866f-47389d07f2fb", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "\n", + "RangeIndex: 288 entries, 0 to 287\n", + "Data columns (total 5 columns):\n", + " # Column Non-Null Count Dtype \n", + "--- ------ -------------- ----- \n", + " 0 identifiers[1].value 288 non-null object \n", + " 1 inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value 288 non-null object \n", + " 2 outcomes[0].products[0].identifiers[0].value 288 non-null object \n", + " 3 outcomes[0].products[0].measurements[0].percentage.value 288 non-null float64\n", + " 4 reaction_id 288 non-null object \n", + "dtypes: float64(1), object(4)\n", + "memory usage: 11.4+ KB\n", + "None\n", + "\n", + "RangeIndex: 288 entries, 0 to 287\n", + "Data columns (total 11 columns):\n", + " # Column Non-Null Count Dtype \n", + "--- ------ -------------- ----- \n", + " 0 identifiers[1].value 288 non-null object \n", + " 1 inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value 288 non-null object \n", + " 2 outcomes[0].products[0].identifiers[0].value 288 non-null object \n", + " 3 outcomes[0].products[0].measurements[0].percentage.value 288 non-null float64\n", + " 4 provenance.record_modified[1].time.value 97 non-null object \n", + " 5 provenance.record_modified[1].person.name 97 non-null object \n", + " 6 provenance.record_modified[1].person.orcid 97 non-null object \n", + " 7 provenance.record_modified[1].person.organization 97 non-null object \n", + " 8 provenance.record_modified[1].person.email 97 non-null object \n", + " 9 provenance.record_modified[1].details 97 non-null object \n", + " 10 reaction_id 288 non-null object \n", + "dtypes: float64(1), object(10)\n", + "memory usage: 24.9+ KB\n", + "None\n" + ] + } + ], + "source": [ + "# Inspect the DataFrame info, the non-null count in record_modified column tells us how many reaction records were updated\n", + "print(df1b.info())\n", + "print(df2b.info())" + ] + }, + { + "cell_type": "code", + "execution_count": 36, + "id": "b70ff442-2d8d-412d-9cfb-935883dfb4ea", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].valueoutcomes[0].products[0].identifiers[0].value
0oldNCCSCc1ccco1CC(NCCSCc1ccco1)c1cccnc1
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194 rows × 2 columns

\n", + "
" + ], + "text/plain": [ + " inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value \\\n", + "0 old NCCSCc1ccco1 \n", + " new NCCSCC1=CC=CO1 \n", + "1 old CC(C)(C)Oc1ccc(CCCN)cc1 \n", + " new NCCCC2=CC=C(C=C2)OC(C)(C)C \n", + "2 old Cc1ccc(S(=O)(=O)CCN)cc1 \n", + "... ... \n", + "188 new OCC1=CN(C2=CC=C(Cl)C=C2)N=N1 \n", + "189 old OCCC1CCN(Cc2ccccc2)C1 \n", + " new OCCC1CCN(CC2=CC=CC=C2)C1 \n", + "196 old CN(C)Cc1c[nH]c2cc(C(=O)O)ccc12 \n", + " new OC(C1=CC(NC=C2CN(C)C)=C2C=C1)=O \n", + "\n", + " outcomes[0].products[0].identifiers[0].value \n", + "0 old CC(NCCSCc1ccco1)c1cccnc1 \n", + " new CC(C1=CC=CN=C1)NCCSCC2=CC=CO2 \n", + "1 old CC(NCCCc1ccc(OC(C)(C)C)cc1)c1cccnc1 \n", + " new CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C \n", + "2 old CC(N[C@H]1CCCC[C@@H]1OCc1ccccc1)c1cccnc1 \n", + "... ... \n", + "188 new ClC%23=CC=C(C=C%23)N%24N=NC(COC(C)C%25=CC=CN=C... \n", + "189 old CC(OCc1cn(-c2ccc(Cl)cc2)nn1)c1cccnc1 \n", + " new CC(C%26=CC=CN=C%26)OCCC%27CCN(CC%28=CC=CC=C%28... \n", + "196 old CC(OC(=O)c1ccc2c(CN(C)C)c[nH]c2c1)c1cccnc1 \n", + " new O=C(C1=CC(NC=C2CN(C)C)=C2C=C1)OC(C)C3=CC=CN=C3 \n", + "\n", + "[194 rows x 2 columns]" + ] + }, + "execution_count": 36, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Compare the DataFrames\n", + "# Select only those columns which are in both DataFrames\n", + "cols_list = ['identifiers[1].value', \n", + " 'inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value', \n", + " 'outcomes[0].products[0].identifiers[0].value', \n", + " 'outcomes[0].products[0].measurements[0].percentage.value', \n", + " 'reaction_id'\n", + " ]\n", + "# Use Pandas df.compare to highlight the differences in row format\n", + "df1b[cols_list].compare(df2b[cols_list], align_axis=0, result_names=('old', 'new'))" + ] + }, + { + "cell_type": "markdown", + "id": "9246181d-e34c-4837-a6f8-c5f6b2f4115d", + "metadata": {}, + "source": [ + "### Reviewing the changes\n", + "\n", + "- df.info() shows that new columns for record_modified meta data have been added\n", + "- 97 non-null count in these columns indicates that 97 reactions were updated\n", + "- df.compare() shows that only the reactant and the product SMILES have been modified (in 194 rows / 2 = 97 reactions). Importantly the reaction_id is unchanged." + ] + }, + { + "cell_type": "markdown", + "id": "bac85da4-e620-400d-ac00-4611f532a3b2", + "metadata": {}, + "source": [ + "## Preparing the dataset for upload to ord-data\n", + "We need to save the updated dataset to a compressed .pb file with the same id" + ] + }, + { + "cell_type": "code", + "execution_count": 39, + "id": "2c0a0eed-8c36-44d6-a823-ea91acb02a42", + "metadata": {}, + "outputs": [], + "source": [ + "# For the purpose of this example the original file had a '_old.pb.gz' suffix. This is removed here to create the target file path\n", + "pb_new_path = './ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz'" + ] + }, + { + "cell_type": "code", + "execution_count": 40, + "id": "cf932cb2-87bf-405d-8e80-dcba2709b14f", + "metadata": {}, + "outputs": [], + "source": [ + "message_helpers.write_message(data2, pb_new_path)" + ] + }, + { + "cell_type": "markdown", + "id": "32fd25db-2493-4a47-80db-1cb2ad1d2e1d", + "metadata": {}, + "source": [ + "From here we use the normal pull request process to replace the existing dataset file in ord-data." + ] + }, + { + "cell_type": "code", + "execution_count": null, + "id": "6760c7a1-f4d1-42fa-97c8-cbd8144acae9", + "metadata": {}, + "outputs": [], + "source": [] + } + ], + "metadata": { + "kernelspec": { + "display_name": "Python 3 (ipykernel)", + "language": "python", + "name": "python3" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.11.7" + } + }, + "nbformat": 4, + "nbformat_minor": 5 +} From d838c8ab1bfe8472c7577546f3aa8f232b631198 Mon Sep 17 00:00:00 2001 From: Ben Deadman Date: Wed, 18 Dec 2024 17:02:31 +0000 Subject: [PATCH 2/7] Revert "Example of updating a dataset" This reverts commit a305364fa095b26cb39a77399070c4adfbfff1c1. --- .../Granda_Perera_ml_example.ipynb | 2 +- .../example_Santanilla.ipynb | 2 +- .../updates/1_Golden/Fig_7_data_corrected.csv | 289 ------ ...set-a12fa15d036d489c971b0b514caeae52.pb.gz | Bin 27096 -> 0 bytes ...a12fa15d036d489c971b0b514caeae52_old.pb.gz | Bin 24772 -> 0 bytes .../updates/1_Golden/update-dataset.ipynb | 937 ------------------ 6 files changed, 2 insertions(+), 1228 deletions(-) delete mode 100644 examples/updates/1_Golden/Fig_7_data_corrected.csv delete mode 100644 examples/updates/1_Golden/ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz delete mode 100644 examples/updates/1_Golden/ord_dataset-a12fa15d036d489c971b0b514caeae52_old.pb.gz delete mode 100644 examples/updates/1_Golden/update-dataset.ipynb diff --git a/examples/applications/Perera_Science_Granda_Nature_Suzuki/Granda_Perera_ml_example.ipynb b/examples/applications/Perera_Science_Granda_Nature_Suzuki/Granda_Perera_ml_example.ipynb index bfd39050d..e235f6411 100644 --- a/examples/applications/Perera_Science_Granda_Nature_Suzuki/Granda_Perera_ml_example.ipynb +++ b/examples/applications/Perera_Science_Granda_Nature_Suzuki/Granda_Perera_ml_example.ipynb @@ -2503,7 +2503,7 @@ "name": "python", "nbconvert_exporter": "python", "pygments_lexer": "ipython3", - "version": "3.11.7" + "version": "3.10.13" } }, "nbformat": 4, diff --git a/examples/submissions/1_Santanilla_Nanomole_HTE/example_Santanilla.ipynb b/examples/submissions/1_Santanilla_Nanomole_HTE/example_Santanilla.ipynb index f42459b5c..0e1efc214 100644 --- a/examples/submissions/1_Santanilla_Nanomole_HTE/example_Santanilla.ipynb +++ b/examples/submissions/1_Santanilla_Nanomole_HTE/example_Santanilla.ipynb @@ -7049,7 +7049,7 @@ "name": "python", "nbconvert_exporter": "python", "pygments_lexer": "ipython3", - "version": "3.11.7" + "version": "3.9.13" } }, "nbformat": 4, diff --git a/examples/updates/1_Golden/Fig_7_data_corrected.csv b/examples/updates/1_Golden/Fig_7_data_corrected.csv deleted file mode 100644 index 9f591f5c7..000000000 --- a/examples/updates/1_Golden/Fig_7_data_corrected.csv +++ /dev/null @@ -1,289 +0,0 @@ -Well,nucleophile_smiles,product_smiles,LCAP -A1,NCCSCC1=CC=CO1,CC(C1=CC=CN=C1)NCCSCC2=CC=CO2,61 -A2,NCCCC2=CC=C(C=C2)OC(C)(C)C,CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C,67 -A3,NCCS(=O)(C3=CC=C(C)C=C3)=O,O=S(CCNC(C)C5=CC=CN=C5)(C6=CC=C(C)C=C6)=O,56 -A4,NCC4(CCOCC4)N5CCCCC5,CC(C7=CC=CN=C7)NCC8(CCOCC8)N9CCCCC9,63 -A5,N[C@@H]6C[C@H]7CC[C@@H]6C7,CC(C%10=CC=CN=C%10)N[C@@H]%11C[C@H]%12CC[C@@H]%11C%12,63 -A6,NCC[C@@H]8CCCN9[C@@H]8CCCC9,CC(C%13=CC=CN=C%13)NCC[C@@H]%14CCCN%15[C@@H]%14CCCC%15,72 -A7,NCCC%10=CCCCC%10,CC(C%16=CC=CN=C%16)NCCC%17=CCCCC%17,33 -A8,N[C@H]%11CCCC[C@@H]%11OCC%12=CC=CC=C%12,CC(C%18=CC=CN=C%18)N[C@H]%19CCCC[C@@H]%19OCC%20=CC=CC=C%20,44 -A9,O=C%13O[C@@H](CN)CN%13C%14=CC(F)=C(N%15CCOCC%15)C=C%14,O=C%21O[C@@H](CNC(C)C%22=CC=CN=C%22)CN%21C%23=CC(F)=C(N%24CCOCC%24)C=C%23,69 -A10,NCC%16(CC%16)C%17=CC(C(F)(F)F)=CC=C%17,CC(C%25=CC=CN=C%25)NCC%26(CC%26)C%27=CC(C(F)(F)F)=CC=C%27,66 -A11,NCCN%18C=CN=N%18,CC(C%28=CC=CN=C%28)NCCN%29C=CN=N%29,52 -A12,O=C([C@H]%19[C@@H]%20C[C@@H](C=C%20)[C@H]%19N)OCC,O=C([C@H]%30[C@@H]%31C[C@@H](C=C%31)[C@H]%30NC(C)C%32=CC=CN=C%32)OCC,43 -B1,NCCN1CCN(c2ccc(Cl)cn2)CC1,CC(NCCN1CCN(c2ccc(Cl)cn2)CC1)c1cccnc1,47 -B2,Cc1cc(C(F)(F)F)nc(CCN)n1,Cc1cc(C(F)(F)F)nc(CCNC(C)c2cccnc2)n1,42 -B3,NCC1C2CN(Cc3ccccc3)CC12,CC(NCC1C2CN(Cc3ccccc3)CC12)c1cccnc1,46 -B4,CN(C)S(=O)(=O)CCN,CC(NCCS(=O)(=O)N(C)C)c1cccnc1,35 -B5,NCCN1CCC(c2ccccc2)C1,CC(NCCN1CCC(c2ccccc2)C1)c1cccnc1,64 -B6,NCCc1cn2cccnc2n1,CC(NCCc1cn2cccnc2n1)c1cccnc1,46 -B7,CCN(CC)C1CCC(N)CC1,CCN(CC)C1CCC(NC(C)c2cccnc2)CC1,68 -B8,NCCN1C(=O)CSC1=O,CC(NCCN1C(=O)CSC1=O)c1cccnc1,58 -B9,NCCN1CCN(c2ncccn2)CC1,CC(NCCN1CCN(c2ncccn2)CC1)c1cccnc1,64 -B10,Cc1cccc(C(C)(C)CN)c1,Cc1cccc(C(C)(C)CNC(C)c2cccnc2)c1,31 -B11,N#Cc1cccc(OCCCN)c1,CC(NCCCOc1cccc(C#N)c1)c1cccnc1,65 -B12,CC(C)c1ccc(CCCN)cc1,CC(C)c1ccc(CCCNC(C)c2cccnc2)cc1,70 -C1,c1cc2c(cc1CN1CCNCC1)OCO2,CC(c1cccnc1)N1CCN(Cc2ccc3c(c2)OCO3)CC1,71 -C2,COc1cccc(N2CCC3(CCNC3)C2)c1,COc1cccc(N2CCC3(CCN(C(C)c4cccnc4)C3)C2)c1,49 -C3,Fc1ccc2onc(C3CCNCC3)c2c1,CC(c1cccnc1)N1CCC(c2noc3ccc(F)cc23)CC1,78 -C4,C1CCNC(CN2CCOCC2)CC1,CC(c1cccnc1)N1CCCCCC1CN1CCOCC1,48 -C5,COc1ccc(CN2CCNCC2)c(OC)c1OC,COc1ccc(CN2CCN(C(C)c3cccnc3)CC2)c(OC)c1OC,84 -C6,c1ccc(-c2ccnc(N3CCNCC3)n2)cc1,CC(c1cccnc1)N1CCN(c2nccc(-c3ccccc3)n2)CC1,50 -C7,CNCC1CCCN(C)C1,CC(c1cccnc1)N(C)CC1CCCN(C)C1,63 -C8,FC1(F)CCN(C2CCNCC2)C1,CC(c1cccnc1)N1CCC(N2CCC(F)(F)C2)CC1,74 -C9,CCc1ncc2n1CCNC2,CCc1ncc2n1CCN(C(C)c1cccnc1)C2,74 -C10,c1ccc2c(N3CCNCC3)nsc2c1,CC(c1cccnc1)N1CCN(c2nsc3ccccc23)CC1,87 -C11,FC(F)(F)c1ccccc1OC1CCNCC1,CC(c1cccnc1)N1CCC(Oc2ccccc2C(F)(F)F)CC1,92 -C12,CCOC(=O)c1ccc(N2CCNCC2)cc1,CCOC(=O)c1ccc(N2CCN(C(C)c3cccnc3)CC2)cc1,62 -D1,CNC1CCNC1,CNC1CCN(C(C)c2cccnc2)C1,76 -D2,CC1(C)CCNC1,CC(c1cccnc1)N1CCC(C)(C)C1,73 -D3,O=S(=O)(N1CCCCC1)N1CCNCC1,CC(c1cccnc1)N1CCN(S(=O)(=O)N2CCCCC2)CC1,43 -D4,CCN1CCNCC1=O,CCN1CCN(C(C)c2cccnc2)CC1=O,87 -D5,CCOC(=O)C1CCN(C2CCNCC2)CC1,CCOC(=O)C1CCN(C2CCN(C(C)c3cccnc3)CC2)CC1,73 -D6,CNCCc1noc(C(C)C)n1,CC(C)c1nc(CCN(C)C(C)c2cccnc2)no1,82 -D7,CSc1ccccc1N1CCNCC1,CSc1ccccc1N1CCN(C(C)c2cccnc2)CC1,68 -D8,FC(F)(F)c1ccc(CC2CCNC2)cc1,CC(c1cccnc1)N1CCC(Cc2ccc(C(F)(F)F)cc2)C1,78 -D9,Fc1cccc(N2C[C@@H]3C[C@H]2CN3)c1,CC(c1cccnc1)N1C[C@@H]2C[C@H]1CN2c1cccc(F)c1,53 -D10,O=C(N1CCNCC1)N1CCOCC1,CC(c1cccnc1)N1CCN(C(=O)N2CCOCC2)CC1,71 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This notebook details the workflow used to update the dataset whilst maintaining the dataset and reaction ids." - ] - }, - { - "cell_type": "code", - "execution_count": 1, - "id": "cbaf6dda-7b56-4110-8fd5-e1ab9bf7aeeb", - "metadata": {}, - "outputs": [], - "source": [ - "# Import modules\n", - "import ord_schema\n", - "from ord_schema import message_helpers, validations, updates\n", - "from ord_schema.proto import dataset_pb2\n", - "from ord_schema.proto import reaction_pb2\n", - "\n", - "import math\n", - "import pandas as pd\n", - "import numpy as np\n", - "import os\n", - "#import wget\n", - "from datetime import datetime\n", - "\n", - "from glob import glob" - ] - }, - { - "cell_type": "markdown", - "id": "e216da23-a415-4682-ac0d-0ba8b58faaa7", - "metadata": {}, - "source": [ - "## Load in the dataset to be updated" - ] - }, - { - "cell_type": "code", - "execution_count": 2, - "id": "d4bbf6d1-01c1-4666-96f9-74938b3edb2a", - "metadata": {}, - "outputs": [], - "source": [ - "# Download the dataset\n", - "# on Linux\n", - "#url = \"https://github.com/open-reaction-database/ord-data/blob/main/data/a1/ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz\"\n", - "#pb = wget.download(url)\n", - "\n", - "# on Windows - manually download the dataset to a directory containing this notebook\n" - ] - }, - { - "cell_type": "code", - "execution_count": 3, - "id": "b6ec3f23-76ec-4a3c-b163-e3258012ca36", - "metadata": {}, - "outputs": [], - "source": [ - "# Load the dataset to be updated\n", - "pb = './ord_dataset-a12fa15d036d489c971b0b514caeae52_old.pb.gz'\n", - "data = message_helpers.load_message(pb, dataset_pb2.Dataset)" - ] - }, - { - "cell_type": "code", - "execution_count": 4, - "id": "a06370cf-8f8a-4a7b-8f7b-1d3830b9145b", - "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "Dataset name is Fig 7 data from Golden paper\n", - "Dataset descripton is Cross-coupling of 3-(1-chloroethyl)pyridine with a range of  nucleophiles. Data from Fig 7 of https://doi.org/10.1016/j.chempr.2024.04.001.\n" - ] - } - ], - "source": [ - "# Inspect the dataset\n", - "print(f\"Dataset name is {data.name}\")\n", - "print(f\"Dataset descripton is {data.description}\")" - ] - }, - { - "cell_type": "code", - "execution_count": 5, - "id": "92178e6c-5a42-4a31-9d37-382f95895fe5", - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "

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284H9O=C(O)c1cn(Cc2ccccc2)nn1CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc191.0ord-0133a2a17eb34832a8f573384e89d644
285H10O=C(O)c1nn(CC2CC2)c2ccccc12CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc171.0ord-c30c707842604783b1da44ea48737140
286H11O=C(O)c1ncn2c1CCCC2CC(OC(=O)c1ncn2c1CCCC2)c1cccnc196.0ord-79706a33f8734f4088c293968ee9782f
287H12C=CCOc1cn(-c2ccccc2)nc1C(=O)OC=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc165.0ord-550018100d194a0aadd041e992676da6
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288 rows × 5 columns

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" - ], - "text/plain": [ - " identifiers[1].value \\\n", - "0 A1 \n", - "1 A2 \n", - "2 A3 \n", - "3 A4 \n", - "4 A5 \n", - ".. ... \n", - "283 H8 \n", - "284 H9 \n", - "285 H10 \n", - "286 H11 \n", - "287 H12 \n", - "\n", - " inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value \\\n", - "0 NCCSCc1ccco1 \n", - "1 CC(C)(C)Oc1ccc(CCCN)cc1 \n", - "2 Cc1ccc(S(=O)(=O)CCN)cc1 \n", - "3 NCC1(N2CCCCC2)CCOCC1 \n", - "4 N[C@@H]1C[C@H]2CC[C@@H]1C2 \n", - ".. ... \n", - "283 Cc1ccccc1-n1ncc(C(=O)O)c1C \n", - "284 O=C(O)c1cn(Cc2ccccc2)nn1 \n", - "285 O=C(O)c1nn(CC2CC2)c2ccccc12 \n", - "286 O=C(O)c1ncn2c1CCCC2 \n", - "287 C=CCOc1cn(-c2ccccc2)nc1C(=O)O \n", - "\n", - " outcomes[0].products[0].identifiers[0].value \\\n", - "0 CC(NCCSCc1ccco1)c1cccnc1 \n", - "1 CC(NCCCc1ccc(OC(C)(C)C)cc1)c1cccnc1 \n", - "2 CC(N[C@H]1CCCC[C@@H]1OCc1ccccc1)c1cccnc1 \n", - "3 Cc1ccc(S(=O)(=O)CCNC(C)c2cccnc2)cc1 \n", - "4 CC(NCC1(N2CCCCC2)CCOCC1)c1cccnc1 \n", - ".. ... \n", - "283 Cc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C \n", - "284 CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc1 \n", - "285 CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc1 \n", - "286 CC(OC(=O)c1ncn2c1CCCC2)c1cccnc1 \n", - "287 C=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc1 \n", - "\n", - " outcomes[0].products[0].measurements[0].percentage.value \\\n", - "0 61.0 \n", - "1 67.0 \n", - "2 56.0 \n", - "3 63.0 \n", - "4 63.0 \n", - ".. ... \n", - "283 81.0 \n", - "284 91.0 \n", - "285 71.0 \n", - "286 96.0 \n", - "287 65.0 \n", - "\n", - " reaction_id \n", - "0 ord-eafdcf86ab4049bdaced8adc28ff4b42 \n", - "1 ord-ab68ccc98d184f9c82b51e02e72399eb \n", - "2 ord-85c8f00118eb4899b36ddc53112d676f \n", - "3 ord-0e5399b5617a489e98405c3172c8779d \n", - "4 ord-ed93dbd8dace4e078573612131d2ef2f \n", - ".. ... \n", - "283 ord-19f1549ea6f44eae96973699b7e6d0a0 \n", - "284 ord-0133a2a17eb34832a8f573384e89d644 \n", - "285 ord-c30c707842604783b1da44ea48737140 \n", - "286 ord-79706a33f8734f4088c293968ee9782f \n", - "287 ord-550018100d194a0aadd041e992676da6 \n", - "\n", - "[288 rows x 5 columns]" - ] - }, - "execution_count": 5, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# To find the messages which need updating it can be helpful to view the dataset as a DataFrame\n", - "# Convert dataset to pandas dataframe\n", - "df = message_helpers.messages_to_dataframe(data.reactions, drop_constant_columns=True)\n", - "\n", - "# View dataframe\n", - "df" - ] - }, - { - "cell_type": "markdown", - "id": "c56d83a4-9862-4df9-b79b-529549e3e2c1", - "metadata": {}, - "source": [ - "### Notes\n", - "The column names can help identify the messages which may be updated." - ] - }, - { - "cell_type": "markdown", - "id": "e91e78eb-aefc-48ef-b768-6bbc87aef99e", - "metadata": {}, - "source": [ - "## Load in the new source data" - ] - }, - { - "cell_type": "code", - "execution_count": 6, - "id": "feb7e488-b983-4278-a509-581a7b281f2b", - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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Wellnucleophile_smilesproduct_smilesLCAP
0A1NCCSCC1=CC=CO1CC(C1=CC=CN=C1)NCCSCC2=CC=CO261
1A2NCCCC2=CC=C(C=C2)OC(C)(C)CCC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C67
2A3NCCS(=O)(C3=CC=C(C)C=C3)=OO=S(CCNC(C)C5=CC=CN=C5)(C6=CC=C(C)C=C6)=O56
3A4NCC4(CCOCC4)N5CCCCC5CC(C7=CC=CN=C7)NCC8(CCOCC8)N9CCCCC963
4A5N[C@@H]6C[C@H]7CC[C@@H]6C7CC(C%10=CC=CN=C%10)N[C@@H]%11C[C@H]%12CC[C@@H]...63
...............
283H8Cc1ccccc1-n1ncc(C(=O)O)c1CCc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C81
284H9O=C(O)c1cn(Cc2ccccc2)nn1CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc191
285H10O=C(O)c1nn(CC2CC2)c2ccccc12CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc171
286H11O=C(O)c1ncn2c1CCCC2CC(OC(=O)c1ncn2c1CCCC2)c1cccnc196
287H12C=CCOc1cn(-c2ccccc2)nc1C(=O)OC=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc165
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288 rows × 4 columns

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" - ], - "text/plain": [ - " Well nucleophile_smiles \\\n", - "0 A1 NCCSCC1=CC=CO1 \n", - "1 A2 NCCCC2=CC=C(C=C2)OC(C)(C)C \n", - "2 A3 NCCS(=O)(C3=CC=C(C)C=C3)=O \n", - "3 A4 NCC4(CCOCC4)N5CCCCC5 \n", - "4 A5 N[C@@H]6C[C@H]7CC[C@@H]6C7 \n", - ".. ... ... \n", - "283 H8 Cc1ccccc1-n1ncc(C(=O)O)c1C \n", - "284 H9 O=C(O)c1cn(Cc2ccccc2)nn1 \n", - "285 H10 O=C(O)c1nn(CC2CC2)c2ccccc12 \n", - "286 H11 O=C(O)c1ncn2c1CCCC2 \n", - "287 H12 C=CCOc1cn(-c2ccccc2)nc1C(=O)O \n", - "\n", - " product_smiles LCAP \n", - "0 CC(C1=CC=CN=C1)NCCSCC2=CC=CO2 61 \n", - "1 CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C 67 \n", - "2 O=S(CCNC(C)C5=CC=CN=C5)(C6=CC=C(C)C=C6)=O 56 \n", - "3 CC(C7=CC=CN=C7)NCC8(CCOCC8)N9CCCCC9 63 \n", - "4 CC(C%10=CC=CN=C%10)N[C@@H]%11C[C@H]%12CC[C@@H]... 63 \n", - ".. ... ... \n", - "283 Cc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C 81 \n", - "284 CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc1 91 \n", - "285 CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc1 71 \n", - "286 CC(OC(=O)c1ncn2c1CCCC2)c1cccnc1 96 \n", - "287 C=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc1 65 \n", - "\n", - "[288 rows x 4 columns]" - ] - }, - "execution_count": 6, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Load in the replacement data\n", - "path = './Fig_7_data_corrected.csv'\n", - "df_replace = pd.read_csv(path)\n", - "df_replace" - ] - }, - { - "cell_type": "markdown", - "id": "60c3f3c4-ef7b-4e99-8779-33ee8774583c", - "metadata": {}, - "source": [ - "### Notes\n", - "We know that some, but not all, of the nucleophile_smiles and product_smiles have been corrected. Well, and LCAP are unchanged." - ] - }, - { - "cell_type": "markdown", - "id": "d521de12-72a5-4ec2-9077-4478dc440234", - "metadata": {}, - "source": [ - "## Update the dataset" - ] - }, - { - "cell_type": "code", - "execution_count": 8, - "id": "048d5f5b-a98e-4dcc-9b3d-852e7ce492bd", - "metadata": {}, - "outputs": [], - "source": [ - "# Make a new copy of the dataset for updating\n", - "data2 = message_helpers.load_message(pb, dataset_pb2.Dataset)" - ] - }, - { - "cell_type": "code", - "execution_count": 9, - "id": "4165bf4c-5408-4ef8-87b9-f170df702673", - "metadata": {}, - "outputs": [], - "source": [ - "# Iterate over the dataset and update reactions\n", - "for index, row in df_replace.iterrows():\n", - " # check if the reaction needs to be updated\n", - " if data.reactions[index].inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value != row['nucleophile_smiles'] or \\\n", - " data.reactions[index].outcomes[0].products[0].identifiers[0].value != row['product_smiles']:\n", - "\n", - " data2.reactions[index].inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value = row['nucleophile_smiles']\n", - " data2.reactions[index].outcomes[0].products[0].identifiers[0].value = row['product_smiles']\n", - " # Add a record_modified event.\n", - " event = data2.reactions[index].provenance.record_modified.add()\n", - " event.time.value = datetime.now().strftime(\"%m/%d/%Y, %H:%M:%S\")\n", - " event.person.CopyFrom(\n", - " reaction_pb2.Person(\n", - " name=\"Benjamin J. Deadman\", organization=\"Open Reaction Database\", orcid=\"0000-0001-8463-8199\", email=\"ben@bjdeadman.co.uk\"\n", - " )\n", - " )\n", - " event.details = \"Corrected the reactant and product SMILES strings\"\n", - " #print(f\"reaction {index} was updated\")\n", - " \n", - " else: \n", - " #print(f\"reaction {index} is unchaged\")\n", - " pass" - ] - }, - { - "cell_type": "code", - "execution_count": 10, - "id": "04b6cab5-d7f8-48c6-b70c-a4c3cbb61438", - "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "type: SMILES\n", - "value: \"NCCCC2=CC=C(C=C2)OC(C)(C)C\"\n", - "\n", - "type: SMILES\n", - "value: \"CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C\"\n", - "\n", - "doi: \"10.1016/j.chempr.2024.04.001\"\n", - "publication_url: \"https://doi.org/10.1016/j.chempr.2024.04.001\"\n", - "record_created {\n", - " time {\n", - " value: \"7/24/2024, 3:36:42 PM\"\n", - " }\n", - " person {\n", - " name: \"Spencer P. Heins\"\n", - " organization: \"UW-Madison\"\n", - " email: \"sheins@wisc.edu\"\n", - " }\n", - "}\n", - "record_modified {\n", - " time {\n", - " value: \"Wed Jul 31 22:03:49 2024\"\n", - " }\n", - " person {\n", - " username: \"github-actions\"\n", - " email: \"github-actions@github.com\"\n", - " }\n", - " details: \"Automatic updates from the submission pipeline.\"\n", - "}\n", - "record_modified {\n", - " time {\n", - " value: \"12/18/2024, 16:17:40\"\n", - " }\n", - " person {\n", - " name: \"Benjamin J. Deadman\"\n", - " orcid: \"0000-0001-8463-8199\"\n", - " organization: \"Open Reaction Database\"\n", - " email: \"ben@bjdeadman.co.uk\"\n", - " }\n", - " details: \"Corrected the reactant and product SMILES strings\"\n", - "}\n", - "\n" - ] - } - ], - "source": [ - "# Inspect a single reaction to view the updated fields in the reaction record\n", - "r_index = 1 # check the reaction at this index\n", - "print(data2.reactions[r_index].inputs[\"Nucleophile in DMF\"].components[0].identifiers[0])\n", - "print(data2.reactions[r_index].outcomes[0].products[0].identifiers[0])\n", - "print(data2.reactions[r_index].provenance)" - ] - }, - { - "cell_type": "markdown", - "id": "73497bf4-4664-4b30-aaed-4f8983393b46", - "metadata": {}, - "source": [ - "## Comparing the datasets" - ] - }, - { - "cell_type": "code", - "execution_count": 14, - "id": "daf8ff8d-4aaf-4748-9ef7-5ec73f2d8d23", - "metadata": {}, - "outputs": [], - "source": [ - "# Convert the datasets to DataFrames, and keep constant columns so that we can see any added messages\n", - "df1 = message_helpers.messages_to_dataframe(data.reactions, drop_constant_columns=False)\n", - "df2 = message_helpers.messages_to_dataframe(data2.reactions, drop_constant_columns=False)" - ] - }, - { - "cell_type": "code", - "execution_count": 18, - "id": "cd9fb8dd-d0cb-48a2-8e27-c2fb9d7a91c2", - "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "(288, 127)\n", - "(288, 133)\n" - ] - } - ], - "source": [ - "# Compare the shape of the DataFrames to confirm that the updated df2 has additional columns for the record_modified metadata\n", - "print(df1.shape)\n", - "print(df2.shape)" - ] - }, - { - "cell_type": "code", - "execution_count": 26, - "id": "c123f794-e164-433f-a7cf-c1bfa908cf20", - "metadata": {}, - "outputs": [], - "source": [ - "# Convert the datasets to compact DataFrames\n", - "df1b = message_helpers.messages_to_dataframe(data.reactions, drop_constant_columns=True)\n", - "df2b = message_helpers.messages_to_dataframe(data2.reactions, drop_constant_columns=True)" - ] - }, - { - "cell_type": "code", - "execution_count": 28, - "id": "b38cedb5-9894-49ae-866f-47389d07f2fb", - "metadata": {}, - "outputs": [ - { - "name": "stdout", - "output_type": "stream", - "text": [ - "\n", - "RangeIndex: 288 entries, 0 to 287\n", - "Data columns (total 5 columns):\n", - " # Column Non-Null Count Dtype \n", - "--- ------ -------------- ----- \n", - " 0 identifiers[1].value 288 non-null object \n", - " 1 inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value 288 non-null object \n", - " 2 outcomes[0].products[0].identifiers[0].value 288 non-null object \n", - " 3 outcomes[0].products[0].measurements[0].percentage.value 288 non-null float64\n", - " 4 reaction_id 288 non-null object \n", - "dtypes: float64(1), object(4)\n", - "memory usage: 11.4+ KB\n", - "None\n", - "\n", - "RangeIndex: 288 entries, 0 to 287\n", - "Data columns (total 11 columns):\n", - " # Column Non-Null Count Dtype \n", - "--- ------ -------------- ----- \n", - " 0 identifiers[1].value 288 non-null object \n", - " 1 inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value 288 non-null object \n", - " 2 outcomes[0].products[0].identifiers[0].value 288 non-null object \n", - " 3 outcomes[0].products[0].measurements[0].percentage.value 288 non-null float64\n", - " 4 provenance.record_modified[1].time.value 97 non-null object \n", - " 5 provenance.record_modified[1].person.name 97 non-null object \n", - " 6 provenance.record_modified[1].person.orcid 97 non-null object \n", - " 7 provenance.record_modified[1].person.organization 97 non-null object \n", - " 8 provenance.record_modified[1].person.email 97 non-null object \n", - " 9 provenance.record_modified[1].details 97 non-null object \n", - " 10 reaction_id 288 non-null object \n", - "dtypes: float64(1), object(10)\n", - "memory usage: 24.9+ KB\n", - "None\n" - ] - } - ], - "source": [ - "# Inspect the DataFrame info, the non-null count in record_modified column tells us how many reaction records were updated\n", - "print(df1b.info())\n", - "print(df2b.info())" - ] - }, - { - "cell_type": "code", - "execution_count": 36, - "id": "b70ff442-2d8d-412d-9cfb-935883dfb4ea", - "metadata": {}, - "outputs": [ - { - "data": { - "text/html": [ - "
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inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].valueoutcomes[0].products[0].identifiers[0].value
0oldNCCSCc1ccco1CC(NCCSCc1ccco1)c1cccnc1
newNCCSCC1=CC=CO1CC(C1=CC=CN=C1)NCCSCC2=CC=CO2
1oldCC(C)(C)Oc1ccc(CCCN)cc1CC(NCCCc1ccc(OC(C)(C)C)cc1)c1cccnc1
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2oldCc1ccc(S(=O)(=O)CCN)cc1CC(N[C@H]1CCCC[C@@H]1OCc1ccccc1)c1cccnc1
............
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194 rows × 2 columns

\n", - "
" - ], - "text/plain": [ - " inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value \\\n", - "0 old NCCSCc1ccco1 \n", - " new NCCSCC1=CC=CO1 \n", - "1 old CC(C)(C)Oc1ccc(CCCN)cc1 \n", - " new NCCCC2=CC=C(C=C2)OC(C)(C)C \n", - "2 old Cc1ccc(S(=O)(=O)CCN)cc1 \n", - "... ... \n", - "188 new OCC1=CN(C2=CC=C(Cl)C=C2)N=N1 \n", - "189 old OCCC1CCN(Cc2ccccc2)C1 \n", - " new OCCC1CCN(CC2=CC=CC=C2)C1 \n", - "196 old CN(C)Cc1c[nH]c2cc(C(=O)O)ccc12 \n", - " new OC(C1=CC(NC=C2CN(C)C)=C2C=C1)=O \n", - "\n", - " outcomes[0].products[0].identifiers[0].value \n", - "0 old CC(NCCSCc1ccco1)c1cccnc1 \n", - " new CC(C1=CC=CN=C1)NCCSCC2=CC=CO2 \n", - "1 old CC(NCCCc1ccc(OC(C)(C)C)cc1)c1cccnc1 \n", - " new CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C \n", - "2 old CC(N[C@H]1CCCC[C@@H]1OCc1ccccc1)c1cccnc1 \n", - "... ... \n", - "188 new ClC%23=CC=C(C=C%23)N%24N=NC(COC(C)C%25=CC=CN=C... \n", - "189 old CC(OCc1cn(-c2ccc(Cl)cc2)nn1)c1cccnc1 \n", - " new CC(C%26=CC=CN=C%26)OCCC%27CCN(CC%28=CC=CC=C%28... \n", - "196 old CC(OC(=O)c1ccc2c(CN(C)C)c[nH]c2c1)c1cccnc1 \n", - " new O=C(C1=CC(NC=C2CN(C)C)=C2C=C1)OC(C)C3=CC=CN=C3 \n", - "\n", - "[194 rows x 2 columns]" - ] - }, - "execution_count": 36, - "metadata": {}, - "output_type": "execute_result" - } - ], - "source": [ - "# Compare the DataFrames\n", - "# Select only those columns which are in both DataFrames\n", - "cols_list = ['identifiers[1].value', \n", - " 'inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value', \n", - " 'outcomes[0].products[0].identifiers[0].value', \n", - " 'outcomes[0].products[0].measurements[0].percentage.value', \n", - " 'reaction_id'\n", - " ]\n", - "# Use Pandas df.compare to highlight the differences in row format\n", - "df1b[cols_list].compare(df2b[cols_list], align_axis=0, result_names=('old', 'new'))" - ] - }, - { - "cell_type": "markdown", - "id": "9246181d-e34c-4837-a6f8-c5f6b2f4115d", - "metadata": {}, - "source": [ - "### Reviewing the changes\n", - "\n", - "- df.info() shows that new columns for record_modified meta data have been added\n", - "- 97 non-null count in these columns indicates that 97 reactions were updated\n", - "- df.compare() shows that only the reactant and the product SMILES have been modified (in 194 rows / 2 = 97 reactions). Importantly the reaction_id is unchanged." - ] - }, - { - "cell_type": "markdown", - "id": "bac85da4-e620-400d-ac00-4611f532a3b2", - "metadata": {}, - "source": [ - "## Preparing the dataset for upload to ord-data\n", - "We need to save the updated dataset to a compressed .pb file with the same id" - ] - }, - { - "cell_type": "code", - "execution_count": 39, - "id": "2c0a0eed-8c36-44d6-a823-ea91acb02a42", - "metadata": {}, - "outputs": [], - "source": [ - "# For the purpose of this example the original file had a '_old.pb.gz' suffix. This is removed here to create the target file path\n", - "pb_new_path = './ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz'" - ] - }, - { - "cell_type": "code", - "execution_count": 40, - "id": "cf932cb2-87bf-405d-8e80-dcba2709b14f", - "metadata": {}, - "outputs": [], - "source": [ - "message_helpers.write_message(data2, pb_new_path)" - ] - }, - { - "cell_type": "markdown", - "id": "32fd25db-2493-4a47-80db-1cb2ad1d2e1d", - "metadata": {}, - "source": [ - "From here we use the normal pull request process to replace the existing dataset file in ord-data." - ] - }, - { - "cell_type": "code", - "execution_count": null, - "id": "6760c7a1-f4d1-42fa-97c8-cbd8144acae9", - "metadata": {}, - "outputs": [], - "source": [] - } - ], - "metadata": { - "kernelspec": { - "display_name": "Python 3 (ipykernel)", - "language": "python", - "name": "python3" - }, - "language_info": { - "codemirror_mode": { - "name": "ipython", - "version": 3 - }, - "file_extension": ".py", - "mimetype": "text/x-python", - "name": "python", - "nbconvert_exporter": "python", - "pygments_lexer": "ipython3", - "version": "3.11.7" - } - }, - "nbformat": 4, - "nbformat_minor": 5 -} From 23cd8e37906b20373cd178c1f2ef5f3b5684c7a8 Mon Sep 17 00:00:00 2001 From: Ben Deadman Date: Wed, 18 Dec 2024 17:09:31 +0000 Subject: [PATCH 3/7] example attempt 2 This push only updates the files required for this example. --- ...set-a12fa15d036d489c971b0b514caeae52.pb.gz | Bin 0 -> 27094 bytes ...a12fa15d036d489c971b0b514caeae52_old.pb.gz | Bin 0 -> 24772 bytes .../updates/1_Golden/update-dataset.ipynb | 937 ++++++++++++++++++ 3 files changed, 937 insertions(+) create mode 100644 examples/updates/1_Golden/ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz create mode 100644 examples/updates/1_Golden/ord_dataset-a12fa15d036d489c971b0b514caeae52_old.pb.gz create mode 100644 examples/updates/1_Golden/update-dataset.ipynb diff --git a/examples/updates/1_Golden/ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz 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This notebook details the workflow used to update the dataset whilst maintaining the dataset and reaction ids." + ] + }, + { + "cell_type": "code", + "execution_count": 1, + "id": "cbaf6dda-7b56-4110-8fd5-e1ab9bf7aeeb", + "metadata": {}, + "outputs": [], + "source": [ + "# Import modules\n", + "import ord_schema\n", + "from ord_schema import message_helpers, validations, updates\n", + "from ord_schema.proto import dataset_pb2\n", + "from ord_schema.proto import reaction_pb2\n", + "\n", + "import math\n", + "import pandas as pd\n", + "import numpy as np\n", + "import os\n", + "#import wget\n", + "from datetime import datetime\n", + "\n", + "from glob import glob" + ] + }, + { + "cell_type": "markdown", + "id": "e216da23-a415-4682-ac0d-0ba8b58faaa7", + "metadata": {}, + "source": [ + "## Load in the dataset to be updated" + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "id": "d4bbf6d1-01c1-4666-96f9-74938b3edb2a", + "metadata": {}, + "outputs": [], + "source": [ + "# Download the dataset\n", + "# on Linux\n", + "#url = \"https://github.com/open-reaction-database/ord-data/blob/main/data/a1/ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz\"\n", + "#pb = wget.download(url)\n", + "\n", + "# on Windows - manually download the dataset to a directory containing this notebook\n" + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "id": "b6ec3f23-76ec-4a3c-b163-e3258012ca36", + "metadata": {}, + "outputs": [], + "source": [ + "# Load the dataset to be updated\n", + "pb = './ord_dataset-a12fa15d036d489c971b0b514caeae52_old.pb.gz'\n", + "data = message_helpers.load_message(pb, dataset_pb2.Dataset)" + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "id": "a06370cf-8f8a-4a7b-8f7b-1d3830b9145b", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Dataset name is Fig 7 data from Golden paper\n", + "Dataset descripton is Cross-coupling of 3-(1-chloroethyl)pyridine with a range of  nucleophiles. Data from Fig 7 of https://doi.org/10.1016/j.chempr.2024.04.001.\n" + ] + } + ], + "source": [ + "# Inspect the dataset\n", + "print(f\"Dataset name is {data.name}\")\n", + "print(f\"Dataset descripton is {data.description}\")" + ] + }, + { + "cell_type": "code", + "execution_count": 5, + "id": "92178e6c-5a42-4a31-9d37-382f95895fe5", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "

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283H8Cc1ccccc1-n1ncc(C(=O)O)c1CCc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C81.0ord-19f1549ea6f44eae96973699b7e6d0a0
284H9O=C(O)c1cn(Cc2ccccc2)nn1CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc191.0ord-0133a2a17eb34832a8f573384e89d644
285H10O=C(O)c1nn(CC2CC2)c2ccccc12CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc171.0ord-c30c707842604783b1da44ea48737140
286H11O=C(O)c1ncn2c1CCCC2CC(OC(=O)c1ncn2c1CCCC2)c1cccnc196.0ord-79706a33f8734f4088c293968ee9782f
287H12C=CCOc1cn(-c2ccccc2)nc1C(=O)OC=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc165.0ord-550018100d194a0aadd041e992676da6
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288 rows × 5 columns

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" + ], + "text/plain": [ + " identifiers[1].value \\\n", + "0 A1 \n", + "1 A2 \n", + "2 A3 \n", + "3 A4 \n", + "4 A5 \n", + ".. ... \n", + "283 H8 \n", + "284 H9 \n", + "285 H10 \n", + "286 H11 \n", + "287 H12 \n", + "\n", + " inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value \\\n", + "0 NCCSCc1ccco1 \n", + "1 CC(C)(C)Oc1ccc(CCCN)cc1 \n", + "2 Cc1ccc(S(=O)(=O)CCN)cc1 \n", + "3 NCC1(N2CCCCC2)CCOCC1 \n", + "4 N[C@@H]1C[C@H]2CC[C@@H]1C2 \n", + ".. ... \n", + "283 Cc1ccccc1-n1ncc(C(=O)O)c1C \n", + "284 O=C(O)c1cn(Cc2ccccc2)nn1 \n", + "285 O=C(O)c1nn(CC2CC2)c2ccccc12 \n", + "286 O=C(O)c1ncn2c1CCCC2 \n", + "287 C=CCOc1cn(-c2ccccc2)nc1C(=O)O \n", + "\n", + " outcomes[0].products[0].identifiers[0].value \\\n", + "0 CC(NCCSCc1ccco1)c1cccnc1 \n", + "1 CC(NCCCc1ccc(OC(C)(C)C)cc1)c1cccnc1 \n", + "2 CC(N[C@H]1CCCC[C@@H]1OCc1ccccc1)c1cccnc1 \n", + "3 Cc1ccc(S(=O)(=O)CCNC(C)c2cccnc2)cc1 \n", + "4 CC(NCC1(N2CCCCC2)CCOCC1)c1cccnc1 \n", + ".. ... \n", + "283 Cc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C \n", + "284 CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc1 \n", + "285 CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc1 \n", + "286 CC(OC(=O)c1ncn2c1CCCC2)c1cccnc1 \n", + "287 C=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc1 \n", + "\n", + " outcomes[0].products[0].measurements[0].percentage.value \\\n", + "0 61.0 \n", + "1 67.0 \n", + "2 56.0 \n", + "3 63.0 \n", + "4 63.0 \n", + ".. ... \n", + "283 81.0 \n", + "284 91.0 \n", + "285 71.0 \n", + "286 96.0 \n", + "287 65.0 \n", + "\n", + " reaction_id \n", + "0 ord-eafdcf86ab4049bdaced8adc28ff4b42 \n", + "1 ord-ab68ccc98d184f9c82b51e02e72399eb \n", + "2 ord-85c8f00118eb4899b36ddc53112d676f \n", + "3 ord-0e5399b5617a489e98405c3172c8779d \n", + "4 ord-ed93dbd8dace4e078573612131d2ef2f \n", + ".. ... \n", + "283 ord-19f1549ea6f44eae96973699b7e6d0a0 \n", + "284 ord-0133a2a17eb34832a8f573384e89d644 \n", + "285 ord-c30c707842604783b1da44ea48737140 \n", + "286 ord-79706a33f8734f4088c293968ee9782f \n", + "287 ord-550018100d194a0aadd041e992676da6 \n", + "\n", + "[288 rows x 5 columns]" + ] + }, + "execution_count": 5, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# To find the messages which need updating it can be helpful to view the dataset as a DataFrame\n", + "# Convert dataset to pandas dataframe\n", + "df = message_helpers.messages_to_dataframe(data.reactions, drop_constant_columns=True)\n", + "\n", + "# View dataframe\n", + "df" + ] + }, + { + "cell_type": "markdown", + "id": "c56d83a4-9862-4df9-b79b-529549e3e2c1", + "metadata": {}, + "source": [ + "### Notes\n", + "The column names can help identify the messages which may be updated." + ] + }, + { + "cell_type": "markdown", + "id": "e91e78eb-aefc-48ef-b768-6bbc87aef99e", + "metadata": {}, + "source": [ + "## Load in the new source data" + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "id": "feb7e488-b983-4278-a509-581a7b281f2b", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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Wellnucleophile_smilesproduct_smilesLCAP
0A1NCCSCC1=CC=CO1CC(C1=CC=CN=C1)NCCSCC2=CC=CO261
1A2NCCCC2=CC=C(C=C2)OC(C)(C)CCC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C67
2A3NCCS(=O)(C3=CC=C(C)C=C3)=OO=S(CCNC(C)C5=CC=CN=C5)(C6=CC=C(C)C=C6)=O56
3A4NCC4(CCOCC4)N5CCCCC5CC(C7=CC=CN=C7)NCC8(CCOCC8)N9CCCCC963
4A5N[C@@H]6C[C@H]7CC[C@@H]6C7CC(C%10=CC=CN=C%10)N[C@@H]%11C[C@H]%12CC[C@@H]...63
...............
283H8Cc1ccccc1-n1ncc(C(=O)O)c1CCc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C81
284H9O=C(O)c1cn(Cc2ccccc2)nn1CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc191
285H10O=C(O)c1nn(CC2CC2)c2ccccc12CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc171
286H11O=C(O)c1ncn2c1CCCC2CC(OC(=O)c1ncn2c1CCCC2)c1cccnc196
287H12C=CCOc1cn(-c2ccccc2)nc1C(=O)OC=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc165
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288 rows × 4 columns

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" + ], + "text/plain": [ + " Well nucleophile_smiles \\\n", + "0 A1 NCCSCC1=CC=CO1 \n", + "1 A2 NCCCC2=CC=C(C=C2)OC(C)(C)C \n", + "2 A3 NCCS(=O)(C3=CC=C(C)C=C3)=O \n", + "3 A4 NCC4(CCOCC4)N5CCCCC5 \n", + "4 A5 N[C@@H]6C[C@H]7CC[C@@H]6C7 \n", + ".. ... ... \n", + "283 H8 Cc1ccccc1-n1ncc(C(=O)O)c1C \n", + "284 H9 O=C(O)c1cn(Cc2ccccc2)nn1 \n", + "285 H10 O=C(O)c1nn(CC2CC2)c2ccccc12 \n", + "286 H11 O=C(O)c1ncn2c1CCCC2 \n", + "287 H12 C=CCOc1cn(-c2ccccc2)nc1C(=O)O \n", + "\n", + " product_smiles LCAP \n", + "0 CC(C1=CC=CN=C1)NCCSCC2=CC=CO2 61 \n", + "1 CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C 67 \n", + "2 O=S(CCNC(C)C5=CC=CN=C5)(C6=CC=C(C)C=C6)=O 56 \n", + "3 CC(C7=CC=CN=C7)NCC8(CCOCC8)N9CCCCC9 63 \n", + "4 CC(C%10=CC=CN=C%10)N[C@@H]%11C[C@H]%12CC[C@@H]... 63 \n", + ".. ... ... \n", + "283 Cc1ccccc1-n1ncc(C(=O)OC(C)c2cccnc2)c1C 81 \n", + "284 CC(OC(=O)c1cn(Cc2ccccc2)nn1)c1cccnc1 91 \n", + "285 CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc1 71 \n", + "286 CC(OC(=O)c1ncn2c1CCCC2)c1cccnc1 96 \n", + "287 C=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc1 65 \n", + "\n", + "[288 rows x 4 columns]" + ] + }, + "execution_count": 6, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Load in the replacement data\n", + "path = './Fig_7_data_corrected.csv'\n", + "df_replace = pd.read_csv(path)\n", + "df_replace" + ] + }, + { + "cell_type": "markdown", + "id": "60c3f3c4-ef7b-4e99-8779-33ee8774583c", + "metadata": {}, + "source": [ + "### Notes\n", + "We know that some, but not all, of the nucleophile_smiles and product_smiles have been corrected. Well, and LCAP are unchanged." + ] + }, + { + "cell_type": "markdown", + "id": "d521de12-72a5-4ec2-9077-4478dc440234", + "metadata": {}, + "source": [ + "## Update the dataset" + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "id": "048d5f5b-a98e-4dcc-9b3d-852e7ce492bd", + "metadata": {}, + "outputs": [], + "source": [ + "# Make a new copy of the dataset for updating\n", + "data2 = message_helpers.load_message(pb, dataset_pb2.Dataset)" + ] + }, + { + "cell_type": "code", + "execution_count": 9, + "id": "4165bf4c-5408-4ef8-87b9-f170df702673", + "metadata": {}, + "outputs": [], + "source": [ + "# Iterate over the dataset and update reactions\n", + "for index, row in df_replace.iterrows():\n", + " # check if the reaction needs to be updated\n", + " if data.reactions[index].inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value != row['nucleophile_smiles'] or \\\n", + " data.reactions[index].outcomes[0].products[0].identifiers[0].value != row['product_smiles']:\n", + "\n", + " data2.reactions[index].inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value = row['nucleophile_smiles']\n", + " data2.reactions[index].outcomes[0].products[0].identifiers[0].value = row['product_smiles']\n", + " # Add a record_modified event.\n", + " event = data2.reactions[index].provenance.record_modified.add()\n", + " event.time.value = datetime.now().strftime(\"%m/%d/%Y, %H:%M:%S\")\n", + " event.person.CopyFrom(\n", + " reaction_pb2.Person(\n", + " name=\"Benjamin J. Deadman\", organization=\"Open Reaction Database\", orcid=\"0000-0001-8463-8199\", email=\"ben@bjdeadman.co.uk\"\n", + " )\n", + " )\n", + " event.details = \"Corrected the reactant and product SMILES strings\"\n", + " #print(f\"reaction {index} was updated\")\n", + " \n", + " else: \n", + " #print(f\"reaction {index} is unchaged\")\n", + " pass" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "id": "04b6cab5-d7f8-48c6-b70c-a4c3cbb61438", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "type: SMILES\n", + "value: \"NCCCC2=CC=C(C=C2)OC(C)(C)C\"\n", + "\n", + "type: SMILES\n", + "value: \"CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C\"\n", + "\n", + "doi: \"10.1016/j.chempr.2024.04.001\"\n", + "publication_url: \"https://doi.org/10.1016/j.chempr.2024.04.001\"\n", + "record_created {\n", + " time {\n", + " value: \"7/24/2024, 3:36:42 PM\"\n", + " }\n", + " person {\n", + " name: \"Spencer P. Heins\"\n", + " organization: \"UW-Madison\"\n", + " email: \"sheins@wisc.edu\"\n", + " }\n", + "}\n", + "record_modified {\n", + " time {\n", + " value: \"Wed Jul 31 22:03:49 2024\"\n", + " }\n", + " person {\n", + " username: \"github-actions\"\n", + " email: \"github-actions@github.com\"\n", + " }\n", + " details: \"Automatic updates from the submission pipeline.\"\n", + "}\n", + "record_modified {\n", + " time {\n", + " value: \"12/18/2024, 16:17:40\"\n", + " }\n", + " person {\n", + " name: \"Benjamin J. Deadman\"\n", + " orcid: \"0000-0001-8463-8199\"\n", + " organization: \"Open Reaction Database\"\n", + " email: \"ben@bjdeadman.co.uk\"\n", + " }\n", + " details: \"Corrected the reactant and product SMILES strings\"\n", + "}\n", + "\n" + ] + } + ], + "source": [ + "# Inspect a single reaction to view the updated fields in the reaction record\n", + "r_index = 1 # check the reaction at this index\n", + "print(data2.reactions[r_index].inputs[\"Nucleophile in DMF\"].components[0].identifiers[0])\n", + "print(data2.reactions[r_index].outcomes[0].products[0].identifiers[0])\n", + "print(data2.reactions[r_index].provenance)" + ] + }, + { + "cell_type": "markdown", + "id": "73497bf4-4664-4b30-aaed-4f8983393b46", + "metadata": {}, + "source": [ + "## Comparing the datasets" + ] + }, + { + "cell_type": "code", + "execution_count": 14, + "id": "daf8ff8d-4aaf-4748-9ef7-5ec73f2d8d23", + "metadata": {}, + "outputs": [], + "source": [ + "# Convert the datasets to DataFrames, and keep constant columns so that we can see any added messages\n", + "df1 = message_helpers.messages_to_dataframe(data.reactions, drop_constant_columns=False)\n", + "df2 = message_helpers.messages_to_dataframe(data2.reactions, drop_constant_columns=False)" + ] + }, + { + "cell_type": "code", + "execution_count": 18, + "id": "cd9fb8dd-d0cb-48a2-8e27-c2fb9d7a91c2", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "(288, 127)\n", + "(288, 133)\n" + ] + } + ], + "source": [ + "# Compare the shape of the DataFrames to confirm that the updated df2 has additional columns for the record_modified metadata\n", + "print(df1.shape)\n", + "print(df2.shape)" + ] + }, + { + "cell_type": "code", + "execution_count": 26, + "id": "c123f794-e164-433f-a7cf-c1bfa908cf20", + "metadata": {}, + "outputs": [], + "source": [ + "# Convert the datasets to compact DataFrames\n", + "df1b = message_helpers.messages_to_dataframe(data.reactions, drop_constant_columns=True)\n", + "df2b = message_helpers.messages_to_dataframe(data2.reactions, drop_constant_columns=True)" + ] + }, + { + "cell_type": "code", + "execution_count": 28, + "id": "b38cedb5-9894-49ae-866f-47389d07f2fb", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "\n", + "RangeIndex: 288 entries, 0 to 287\n", + "Data columns (total 5 columns):\n", + " # Column Non-Null Count Dtype \n", + "--- ------ -------------- ----- \n", + " 0 identifiers[1].value 288 non-null object \n", + " 1 inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value 288 non-null object \n", + " 2 outcomes[0].products[0].identifiers[0].value 288 non-null object \n", + " 3 outcomes[0].products[0].measurements[0].percentage.value 288 non-null float64\n", + " 4 reaction_id 288 non-null object \n", + "dtypes: float64(1), object(4)\n", + "memory usage: 11.4+ KB\n", + "None\n", + "\n", + "RangeIndex: 288 entries, 0 to 287\n", + "Data columns (total 11 columns):\n", + " # Column Non-Null Count Dtype \n", + "--- ------ -------------- ----- \n", + " 0 identifiers[1].value 288 non-null object \n", + " 1 inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value 288 non-null object \n", + " 2 outcomes[0].products[0].identifiers[0].value 288 non-null object \n", + " 3 outcomes[0].products[0].measurements[0].percentage.value 288 non-null float64\n", + " 4 provenance.record_modified[1].time.value 97 non-null object \n", + " 5 provenance.record_modified[1].person.name 97 non-null object \n", + " 6 provenance.record_modified[1].person.orcid 97 non-null object \n", + " 7 provenance.record_modified[1].person.organization 97 non-null object \n", + " 8 provenance.record_modified[1].person.email 97 non-null object \n", + " 9 provenance.record_modified[1].details 97 non-null object \n", + " 10 reaction_id 288 non-null object \n", + "dtypes: float64(1), object(10)\n", + "memory usage: 24.9+ KB\n", + "None\n" + ] + } + ], + "source": [ + "# Inspect the DataFrame info, the non-null count in record_modified column tells us how many reaction records were updated\n", + "print(df1b.info())\n", + "print(df2b.info())" + ] + }, + { + "cell_type": "code", + "execution_count": 36, + "id": "b70ff442-2d8d-412d-9cfb-935883dfb4ea", + "metadata": {}, + "outputs": [ + { + "data": { + "text/html": [ + "
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inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].valueoutcomes[0].products[0].identifiers[0].value
0oldNCCSCc1ccco1CC(NCCSCc1ccco1)c1cccnc1
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194 rows × 2 columns

\n", + "
" + ], + "text/plain": [ + " inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value \\\n", + "0 old NCCSCc1ccco1 \n", + " new NCCSCC1=CC=CO1 \n", + "1 old CC(C)(C)Oc1ccc(CCCN)cc1 \n", + " new NCCCC2=CC=C(C=C2)OC(C)(C)C \n", + "2 old Cc1ccc(S(=O)(=O)CCN)cc1 \n", + "... ... \n", + "188 new OCC1=CN(C2=CC=C(Cl)C=C2)N=N1 \n", + "189 old OCCC1CCN(Cc2ccccc2)C1 \n", + " new OCCC1CCN(CC2=CC=CC=C2)C1 \n", + "196 old CN(C)Cc1c[nH]c2cc(C(=O)O)ccc12 \n", + " new OC(C1=CC(NC=C2CN(C)C)=C2C=C1)=O \n", + "\n", + " outcomes[0].products[0].identifiers[0].value \n", + "0 old CC(NCCSCc1ccco1)c1cccnc1 \n", + " new CC(C1=CC=CN=C1)NCCSCC2=CC=CO2 \n", + "1 old CC(NCCCc1ccc(OC(C)(C)C)cc1)c1cccnc1 \n", + " new CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C \n", + "2 old CC(N[C@H]1CCCC[C@@H]1OCc1ccccc1)c1cccnc1 \n", + "... ... \n", + "188 new ClC%23=CC=C(C=C%23)N%24N=NC(COC(C)C%25=CC=CN=C... \n", + "189 old CC(OCc1cn(-c2ccc(Cl)cc2)nn1)c1cccnc1 \n", + " new CC(C%26=CC=CN=C%26)OCCC%27CCN(CC%28=CC=CC=C%28... \n", + "196 old CC(OC(=O)c1ccc2c(CN(C)C)c[nH]c2c1)c1cccnc1 \n", + " new O=C(C1=CC(NC=C2CN(C)C)=C2C=C1)OC(C)C3=CC=CN=C3 \n", + "\n", + "[194 rows x 2 columns]" + ] + }, + "execution_count": 36, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Compare the DataFrames\n", + "# Select only those columns which are in both DataFrames\n", + "cols_list = ['identifiers[1].value', \n", + " 'inputs[\"Nucleophile in DMF\"].components[0].identifiers[0].value', \n", + " 'outcomes[0].products[0].identifiers[0].value', \n", + " 'outcomes[0].products[0].measurements[0].percentage.value', \n", + " 'reaction_id'\n", + " ]\n", + "# Use Pandas df.compare to highlight the differences in row format\n", + "df1b[cols_list].compare(df2b[cols_list], align_axis=0, result_names=('old', 'new'))" + ] + }, + { + "cell_type": "markdown", + "id": "9246181d-e34c-4837-a6f8-c5f6b2f4115d", + "metadata": {}, + "source": [ + "### Reviewing the changes\n", + "\n", + "- df.info() shows that new columns for record_modified meta data have been added\n", + "- 97 non-null count in these columns indicates that 97 reactions were updated\n", + "- df.compare() shows that only the reactant and the product SMILES have been modified (in 194 rows / 2 = 97 reactions). Importantly the reaction_id is unchanged." + ] + }, + { + "cell_type": "markdown", + "id": "bac85da4-e620-400d-ac00-4611f532a3b2", + "metadata": {}, + "source": [ + "## Preparing the dataset for upload to ord-data\n", + "We need to save the updated dataset to a compressed .pb file with the same id" + ] + }, + { + "cell_type": "code", + "execution_count": 39, + "id": "2c0a0eed-8c36-44d6-a823-ea91acb02a42", + "metadata": {}, + "outputs": [], + "source": [ + "# For the purpose of this example the original file had a '_old.pb.gz' suffix. This is removed here to create the target file path\n", + "pb_new_path = './ord_dataset-a12fa15d036d489c971b0b514caeae52.pb.gz'" + ] + }, + { + "cell_type": "code", + "execution_count": 40, + "id": "cf932cb2-87bf-405d-8e80-dcba2709b14f", + "metadata": {}, + "outputs": [], + "source": [ + "message_helpers.write_message(data2, pb_new_path)" + ] + }, + { + "cell_type": "markdown", + "id": "32fd25db-2493-4a47-80db-1cb2ad1d2e1d", + "metadata": {}, + "source": [ + "From here we use the normal pull request process to replace the existing dataset file in ord-data." + ] + }, + { + "cell_type": "code", + "execution_count": null, + "id": "6760c7a1-f4d1-42fa-97c8-cbd8144acae9", + "metadata": {}, + "outputs": [], + "source": [] + } + ], + "metadata": { + "kernelspec": { + "display_name": "Python 3 (ipykernel)", + "language": "python", + "name": "python3" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.11.7" + } + }, + "nbformat": 4, + "nbformat_minor": 5 +} From 8443159a62d1c8a86745d0615e74fd3f6886e6a4 Mon Sep 17 00:00:00 2001 From: Ben Deadman Date: Wed, 18 Dec 2024 17:10:05 +0000 Subject: [PATCH 4/7] tidying up --- .../updates/1_Golden/update-dataset.ipynb | 24 +++++++++---------- 1 file changed, 12 insertions(+), 12 deletions(-) diff --git a/examples/updates/1_Golden/update-dataset.ipynb b/examples/updates/1_Golden/update-dataset.ipynb index 03245c4ba..cc3f90237 100644 --- a/examples/updates/1_Golden/update-dataset.ipynb +++ b/examples/updates/1_Golden/update-dataset.ipynb @@ -500,7 +500,7 @@ }, { "cell_type": "code", - "execution_count": 8, + "execution_count": 7, "id": "048d5f5b-a98e-4dcc-9b3d-852e7ce492bd", "metadata": {}, "outputs": [], @@ -511,7 +511,7 @@ }, { "cell_type": "code", - "execution_count": 9, + "execution_count": 8, "id": "4165bf4c-5408-4ef8-87b9-f170df702673", "metadata": {}, "outputs": [], @@ -542,7 +542,7 @@ }, { "cell_type": "code", - "execution_count": 10, + "execution_count": 9, "id": "04b6cab5-d7f8-48c6-b70c-a4c3cbb61438", "metadata": {}, "outputs": [ @@ -580,7 +580,7 @@ "}\n", "record_modified {\n", " time {\n", - " value: \"12/18/2024, 16:17:40\"\n", + " value: \"12/18/2024, 17:08:03\"\n", " }\n", " person {\n", " name: \"Benjamin J. Deadman\"\n", @@ -612,7 +612,7 @@ }, { "cell_type": "code", - "execution_count": 14, + "execution_count": 10, "id": "daf8ff8d-4aaf-4748-9ef7-5ec73f2d8d23", "metadata": {}, "outputs": [], @@ -624,7 +624,7 @@ }, { "cell_type": "code", - "execution_count": 18, + "execution_count": 11, "id": "cd9fb8dd-d0cb-48a2-8e27-c2fb9d7a91c2", "metadata": {}, "outputs": [ @@ -645,7 +645,7 @@ }, { "cell_type": "code", - "execution_count": 26, + "execution_count": 12, "id": "c123f794-e164-433f-a7cf-c1bfa908cf20", "metadata": {}, "outputs": [], @@ -657,7 +657,7 @@ }, { "cell_type": "code", - "execution_count": 28, + "execution_count": 13, "id": "b38cedb5-9894-49ae-866f-47389d07f2fb", "metadata": {}, "outputs": [ @@ -708,7 +708,7 @@ }, { "cell_type": "code", - "execution_count": 36, + "execution_count": 14, "id": "b70ff442-2d8d-412d-9cfb-935883dfb4ea", "metadata": {}, "outputs": [ @@ -836,7 +836,7 @@ "[194 rows x 2 columns]" ] }, - "execution_count": 36, + "execution_count": 14, "metadata": {}, "output_type": "execute_result" } @@ -877,7 +877,7 @@ }, { "cell_type": "code", - "execution_count": 39, + "execution_count": 15, "id": "2c0a0eed-8c36-44d6-a823-ea91acb02a42", "metadata": {}, "outputs": [], @@ -888,7 +888,7 @@ }, { "cell_type": "code", - "execution_count": 40, + "execution_count": 16, "id": "cf932cb2-87bf-405d-8e80-dcba2709b14f", "metadata": {}, "outputs": [], From ff508db8bb67c5f44d1f5a00a3dfe096fcd5dea0 Mon Sep 17 00:00:00 2001 From: Ben Deadman Date: Wed, 18 Dec 2024 17:10:18 +0000 Subject: [PATCH 5/7] Create Fig_7_data_corrected.csv --- .../updates/1_Golden/Fig_7_data_corrected.csv | 289 ++++++++++++++++++ 1 file changed, 289 insertions(+) create mode 100644 examples/updates/1_Golden/Fig_7_data_corrected.csv diff --git a/examples/updates/1_Golden/Fig_7_data_corrected.csv b/examples/updates/1_Golden/Fig_7_data_corrected.csv new file mode 100644 index 000000000..9f591f5c7 --- /dev/null +++ b/examples/updates/1_Golden/Fig_7_data_corrected.csv @@ -0,0 +1,289 @@ +Well,nucleophile_smiles,product_smiles,LCAP +A1,NCCSCC1=CC=CO1,CC(C1=CC=CN=C1)NCCSCC2=CC=CO2,61 +A2,NCCCC2=CC=C(C=C2)OC(C)(C)C,CC(C3=CC=CN=C3)NCCCC4=CC=C(C=C4)OC(C)(C)C,67 +A3,NCCS(=O)(C3=CC=C(C)C=C3)=O,O=S(CCNC(C)C5=CC=CN=C5)(C6=CC=C(C)C=C6)=O,56 +A4,NCC4(CCOCC4)N5CCCCC5,CC(C7=CC=CN=C7)NCC8(CCOCC8)N9CCCCC9,63 +A5,N[C@@H]6C[C@H]7CC[C@@H]6C7,CC(C%10=CC=CN=C%10)N[C@@H]%11C[C@H]%12CC[C@@H]%11C%12,63 +A6,NCC[C@@H]8CCCN9[C@@H]8CCCC9,CC(C%13=CC=CN=C%13)NCC[C@@H]%14CCCN%15[C@@H]%14CCCC%15,72 +A7,NCCC%10=CCCCC%10,CC(C%16=CC=CN=C%16)NCCC%17=CCCCC%17,33 +A8,N[C@H]%11CCCC[C@@H]%11OCC%12=CC=CC=C%12,CC(C%18=CC=CN=C%18)N[C@H]%19CCCC[C@@H]%19OCC%20=CC=CC=C%20,44 +A9,O=C%13O[C@@H](CN)CN%13C%14=CC(F)=C(N%15CCOCC%15)C=C%14,O=C%21O[C@@H](CNC(C)C%22=CC=CN=C%22)CN%21C%23=CC(F)=C(N%24CCOCC%24)C=C%23,69 +A10,NCC%16(CC%16)C%17=CC(C(F)(F)F)=CC=C%17,CC(C%25=CC=CN=C%25)NCC%26(CC%26)C%27=CC(C(F)(F)F)=CC=C%27,66 +A11,NCCN%18C=CN=N%18,CC(C%28=CC=CN=C%28)NCCN%29C=CN=N%29,52 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+H10,O=C(O)c1nn(CC2CC2)c2ccccc12,CC(OC(=O)c1nn(CC2CC2)c2ccccc12)c1cccnc1,71 +H11,O=C(O)c1ncn2c1CCCC2,CC(OC(=O)c1ncn2c1CCCC2)c1cccnc1,96 +H12,C=CCOc1cn(-c2ccccc2)nc1C(=O)O,C=CCOc1cn(-c2ccccc2)nc1C(=O)OC(C)c1cccnc1,65 From 3203eb4a745f15deff4e3ee914418e240738273c Mon Sep 17 00:00:00 2001 From: Ben Deadman Date: Mon, 20 Jan 2025 15:35:01 +1300 Subject: [PATCH 6/7] Example of enumeration a template file Example enumerating over 2 template files (to account for differences in reaction analysis), and then merging the dataset. --- .../11_enumeration_of_template/aza_heck.xlsx | Bin 0 -> 11065 bytes .../aza_heck_w_nmr.xlsx | Bin 0 -> 9933 bytes .../dataset_1.pbtxt | 7974 ++++++++++++ .../dataset_2.pbtxt | 2308 ++++ .../enumeration.ipynb | 778 ++ .../merged_dataset.pbtxt | 10280 ++++++++++++++++ .../template_nmr_v2.1.pbtxt | 461 + .../template_v2.1.pbtxt | 419 + 8 files changed, 22220 insertions(+) create mode 100644 examples/submissions/11_enumeration_of_template/aza_heck.xlsx create mode 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synthesis of Impatien A" +description: "24 ligands are screened for the aza-Heck cyclization in a total synthesis of Impatien A." +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "Al" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Triisobutylphosphatrane" + } + identifiers { + type: SMILES + value: "CC(C)CN1CCN2CCN(CC(C)C)P1N(CC2)CC(C)C" + } + identifiers { + type: CAS_NUMBER + value: "331465-71-5" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "A2" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Tris(4-methoxyphenyl)phosphine" + } + identifiers { + type: SMILES + value: "COc1ccc(cc1)P(c2ccc(OC)cc2)c3ccc(OC)cc3" + } + identifiers { + type: CAS_NUMBER + value: "855-38-9" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "A3" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Triphenylphosphine" + } + identifiers { + type: SMILES + value: "c1ccccc1P(c2ccccc2)c3ccccc3" + } + identifiers { + type: CAS_NUMBER + value: "603-35-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "A4" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Triphenylphosphite" + } + identifiers { + type: SMILES + value: "C1=CC=C(C=C1)OP(OC2=CC=CC=C2)OC3=CC=CC=C3" + } + identifiers { + type: CAS_NUMBER + value: "101-02-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "A6" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "2,2\342\200\262-Methylenebis[(4S)-4-phenyl-2-oxazoline]" + } + identifiers { + type: SMILES + value: "C1[C@@H](N=C(O1)CC2=N[C@H](CO2)C3=CC=CC=C3)C4=CC=CC=C4" + } + identifiers { + type: CAS_NUMBER + value: "132098-59-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B1" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Tribenzylphosphine" + } + identifiers { + type: SMILES + value: "C1=CC=C(C=C1)CP(CC2=CC=CC=C2)CC3=CC=CC=C3" + } + identifiers { + type: CAS_NUMBER + value: "7650-89-7" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B2" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Bis[(2-diphenylphosphino)phenyl] ether" + } + identifiers { + type: SMILES + value: "C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3OC4=CC=CC=C4P(C5=CC=CC=C5)C6=CC=CC=C6" + } + identifiers { + type: CAS_NUMBER + value: "166330-10-5" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B3" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(S)-PipPhos" + } + identifiers { + type: SMILES + value: "C1CCN(CC1)P2OC3=C(C4=CC=CC=C4C=C3)C5=C(O2)C=CC6=CC=CC=C65" + } + identifiers { + type: CAS_NUMBER + value: "284472-79-3" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B6" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(S)-4-tert-Butyl-2-[2-(diphenyl-\nphosphino)phenyl]-2-oxazoline" + } + identifiers { + type: SMILES + value: "CC(C)(C)[C@H]1COC(=N1)C2=CC=CC=C2P(C3=CC=CC=C3)C4=CC=CC=C4" + } + identifiers { + type: CAS_NUMBER + value: "148461-16-9" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "Cl" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "CyJohnPhos" + } + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4" + } + identifiers { + type: CAS_NUMBER + value: "247940-06-3" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C2" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "CagePhos" + } + identifiers { + type: SMILES + value: "CC12COP(OC1)OC2" + } + identifiers { + type: CAS_NUMBER + value: "1449-91-8" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C3" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "P(tBu)(3,5-bisCF3Ph)2" + } + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1)C2=CC(C(F)(F)F)=CC(C(F)(F)F)=C2" + } + identifiers { + type: CAS_NUMBER + value: "1616979-85-1" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C4" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "P(p-FPh)3" + } + identifiers { + type: SMILES + value: "C1=CC(=CC=C1F)P(C2=CC=C(C=C2)F)C3=CC=C(C=C3)F" + } + identifiers { + type: CAS_NUMBER + value: "18437-78-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C6" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "BIPOL-Al (R)" + } + identifiers { + type: SMILES + value: "COC1=C(C2=CC=CC=C2C=C1)C3=C(C=CC4=CC=CC=C43)P(C5=CC=CC=C5)C6=CC=CC=C6" + } + identifiers { + type: CAS_NUMBER + value: "500103-26-4" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D1" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(R)-MOP" + } + identifiers { + type: SMILES + value: "COC1=C(C2=CC=CC=C2C=C1)C3=C(C=CC4=CC=CC=C43)P(C5=CC=CC=C5)C6=CC=CC=C6" + } + identifiers { + type: CAS_NUMBER + value: "145964-33-6" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D3" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(S)-FuP-tBu" + } + identifiers { + type: SMILES + value: "CC(C)(C)P1OC2=CC=CC3=C2C4(CC3)CCC5=C4C(=CC=C5)O1" + } + identifiers { + type: CAS_NUMBER + value: "912457-08-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D4" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "1,3,5,7-Tetramethy1-6-pheny1-\n2,4,8-trioxa-6-\nphosphaadamantane" + } + identifiers { + type: SMILES + value: "C[C@@]1(C2)P(C3=CC=CC=C3)[C@]4(C)O[C@@]2(C)O[C@@](C)(C4)O1" + } + identifiers { + type: CAS_NUMBER + value: "977739-46-3" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D5" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(R)-BTFM-Garphos" + } + identifiers { + type: SMILES + value: "COC1=CC(=C(C(=C1)P(C2=CC(=CC(=C2)C(F)(F)F)C(F)(F)F)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C4=C(C=C(C=C4P(C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F)C6=CC(=CC(=C6)C(F)(F)F)C(F)(F)F)OC)OC)OC" + } + identifiers { + type: CAS_NUMBER + value: "1365531-84-5" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D6" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "No ligand" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} diff --git a/examples/submissions/11_enumeration_of_template/dataset_2.pbtxt b/examples/submissions/11_enumeration_of_template/dataset_2.pbtxt new file mode 100644 index 000000000..0af79baf6 --- /dev/null +++ b/examples/submissions/11_enumeration_of_template/dataset_2.pbtxt @@ -0,0 +1,2308 @@ +name: "Ligand screening for Aza-Heck cyclization in total synthesis of Impatien A" +description: "24 ligands are screened for the aza-Heck cyclization in a total synthesis of Impatien A." +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "AS" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Tris[3,5-bis(trifluoromethyl)phenyl]phosphine" + } + identifiers { + type: SMILES + value: "C1=C(C=C(C=C1C(F)(F)F)P(C2=CC(=CC(=C2)C(F)(F)F)C(F)(F)F)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C(F)(F)F" + } + identifiers { + type: CAS_NUMBER + value: "175136-62-6" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B4" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(3aR,8aR)-(-)-(2,2-Dimethy1-\n4,4,8,8-tetraphenyl-tetrahydro-\n[1,3]dioxolo-[4,5-e][1,3,2]-\ndioxaphosphepin-6-\ny1)dimethylamine" + } + identifiers { + type: SMILES + value: "CC1(O[C@@H]2[C@@H](O1)C(OP(OC2(C3=CC=CC=C3)C4=CC=CC=C4)N(C)C)(C5=CC=CC=C5)C6=CC=CC=C6)C" + } + identifiers { + type: CAS_NUMBER + value: "213843-90-4" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B5" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(R)-1,1\342\200\231-binaphthyl-2,2\342\200\231-diyl ethyl phosphite" + } + identifiers { + type: SMILES + value: "CCOP1OC2=C(C3=C(C=CC4=CC=CC=C43)O1)C5=CC=CC=C5C=C2" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C5" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "JackiePhos" + } + identifiers { + type: SMILES + value: "CC(C)C1=CC(=C(C(=C1)C(C)C)C2=C(C=CC(=C2P(C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)OC)OC)C(C)C" + } + identifiers { + type: CAS_NUMBER + value: "1160861-60-8" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D2" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(R)-ShiP" + } + identifiers { + type: SMILES + value: "C1CC23CCC4=C2C(=CC=C4)OP(OC5=CC=CC1=C35)OC6=CC=CC=C6" + } + identifiers { + type: CAS_NUMBER + value: "656233-53-3" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} diff --git a/examples/submissions/11_enumeration_of_template/enumeration.ipynb b/examples/submissions/11_enumeration_of_template/enumeration.ipynb new file mode 100644 index 000000000..3b68670f2 --- /dev/null +++ b/examples/submissions/11_enumeration_of_template/enumeration.ipynb @@ -0,0 +1,778 @@ +{ + "cells": [ + { + "cell_type": "markdown", + "id": "c2206846-6f1e-4097-b141-6742c339715d", + "metadata": {}, + "source": [ + "# Enumeration of a Template Reaction Over a CSV File" + ] + }, + { + "cell_type": "markdown", + "id": "a6aa24e3-9111-4c51-87a1-829819e5c283", + "metadata": {}, + "source": [ + "This example demonstrates how to enumerate a template reaction over a spreadsheet file in Python. This operation can also be achieved using the onlne ORD editor, but sometimes it is useful to run the enumeration locally. In this case we are also running the enumeration over 2 separate templates to account for differences in which ananlysis was conducted. The 2 datasets are subsequently merged into a single dataset." + ] + }, + { + "cell_type": "markdown", + "id": "c992eda2-f405-4ebc-a092-5a7a215398c5", + "metadata": {}, + "source": [ + "## Setup" + ] + }, + { + "cell_type": "code", + "execution_count": 1, + "id": "cb3c6e2f-f55c-4e36-83d1-d2e9a7e6ea4b", + "metadata": {}, + "outputs": [], + "source": [ + "# from the enumeration script\n", + "import docopt\n", + "import numpy as np\n", + "\n", + "from ord_schema import message_helpers, templating, validations\n", + "from ord_schema.logging import get_logger\n", + "from ord_schema.proto import dataset_pb2, reaction_pb2\n", + "\n", + "logger = get_logger(__name__)" + ] + }, + { + "cell_type": "code", + "execution_count": 2, + "id": "cfba7c96-9a49-430d-935c-d76cd384e910", + "metadata": {}, + "outputs": [], + "source": [ + "# code modified from enumeration script in ord-schema\n", + "def enumerate_dataset(template, data, output):\n", + " with open(template) as f:\n", + " template_string = f.read()\n", + " df = templating.read_spreadsheet(data)\n", + " logger.info(\n", + " \"generating new Dataset from %s and %s\",\n", + " template,\n", + " data,\n", + " )\n", + " dataset = templating.generate_dataset(\n", + " name= name,\n", + " description= description,\n", + " template_string= template_string,\n", + " df=df,\n", + " validate= True,\n", + " )\n", + " logger.info(\"writing new Dataset to %s\", output)\n", + " message_helpers.write_message(dataset, output)" + ] + }, + { + "cell_type": "markdown", + "id": "32dbe6f8-be54-4a1f-b5cc-4265e435cd7f", + "metadata": {}, + "source": [ + "## Enumeration" + ] + }, + { + "cell_type": "code", + "execution_count": 3, + "id": "baaf89ef-02b5-42e8-a78a-dad9bc2a34b6", + "metadata": {}, + "outputs": [], + "source": [ + "# specify the dataset name and description\n", + "name = 'Ligand screening for Aza-Heck cyclization in total synthesis of Impatien A'\n", + "description = '24 ligands are screened for the aza-Heck cyclization in a total synthesis of Impatien A.'" + ] + }, + { + "cell_type": "code", + "execution_count": 4, + "id": "fe272181-075c-48dd-94e7-84c46e565c44", + "metadata": {}, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "INFO 2025-01-20 15:25:15,270 1297433464.py:6: generating new Dataset from ./template_v2.1.pbtxt and ./aza_heck.xlsx\n", + "INFO 2025-01-20 15:25:15,616 1297433464.py:18: writing new Dataset to dataset_1.pbtxt\n" + ] + } + ], + "source": [ + "# Enumerate the main set of reactions\n", + "enumerate_dataset('./template_v2.1.pbtxt', './aza_heck.xlsx', 'dataset_1.pbtxt')" + ] + }, + { + "cell_type": "code", + "execution_count": 5, + "id": "add07e99-bb9f-4fe1-8ebc-0f38d1e4b0dc", + "metadata": {}, + "outputs": [ + { + "name": "stderr", + "output_type": "stream", + "text": [ + "INFO 2025-01-20 15:25:16,863 1297433464.py:6: generating new Dataset from ./template_nmr_v2.1.pbtxt and ./aza_heck_w_nmr.xlsx\n", + "INFO 2025-01-20 15:25:16,957 1297433464.py:18: writing new Dataset to dataset_2.pbtxt\n" + ] + } + ], + "source": [ + "# Enumerate the subset of reactions that also have NMR data\n", + "enumerate_dataset('./template_nmr_v2.1.pbtxt', './aza_heck_w_nmr.xlsx', 'dataset_2.pbtxt')" + ] + }, + { + "cell_type": "markdown", + "id": "35856aca-cb17-4c1a-b375-8824cfe81757", + "metadata": {}, + "source": [ + "## Merge the dataset files" + ] + }, + { + "cell_type": "code", + "execution_count": 6, + "id": "90ef7f20-40e2-40c2-b737-232a6e24fd5a", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Dataset has 19 reactions\n" + ] + } + ], + "source": [ + "# Open the primary dataset file\n", + "pb = './dataset_1.pbtxt'\n", + "primary = message_helpers.load_message(pb, dataset_pb2.Dataset)\n", + "print(f\"Dataset has {len(primary.reactions)} reactions\")" + ] + }, + { + "cell_type": "code", + "execution_count": 7, + "id": "8817cb42-85e1-4232-b2d2-bb76c61c4f0f", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Dataset has 5 reactions\n" + ] + } + ], + "source": [ + "# open the dataset to be added to the primary dataset\n", + "pb_2 = './dataset_2.pbtxt'\n", + "secondary = message_helpers.load_message(pb_2, dataset_pb2.Dataset)\n", + "print(f\"Dataset has {len(secondary.reactions)} reactions\")" + ] + }, + { + "cell_type": "code", + "execution_count": 8, + "id": "aced3174-b5ae-4598-b39a-96ce7428a178", + "metadata": {}, + "outputs": [], + "source": [ + "merged_dataset = primary\n", + "for rxn in secondary.reactions:\n", + " merged_dataset.reactions.append(rxn)" + ] + }, + { + "cell_type": "code", + "execution_count": 9, + "id": "f1d2b305-2c5e-445f-8534-85033b900c73", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Dataset has 24 reactions\n" + ] + } + ], + "source": [ + "#Check the size of the new dataset\n", + "print(f\"Dataset has {len(merged_dataset.reactions)} reactions\")" + ] + }, + { + "cell_type": "code", + "execution_count": 10, + "id": "d6e08509-6736-4e38-ba5a-b050d02efa18", + "metadata": {}, + "outputs": [], + "source": [ + "message_helpers.write_message(merged_dataset, './merged_dataset.pbtxt')" + ] + }, + { + "cell_type": "markdown", + "id": "d777d778-1453-434d-acc8-7d0d414ec4fc", + "metadata": {}, + "source": [ + "## Review the Results" + ] + }, + { + "cell_type": "code", + "execution_count": 11, + "id": "5fe8d90d-3555-4c5c-bd99-09e701fdb98c", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Dataset has 24 reactions\n" + ] + } + ], + "source": [ + "#Check the size of the new dataset\n", + "print(f\"Dataset has {len(merged_dataset.reactions)} reactions\")" + ] + }, + { + "cell_type": "code", + "execution_count": 12, + "id": "51d9dac7-d99b-4b24-902f-b83dd566988d", + "metadata": {}, + "outputs": [], + "source": [ + "# Validate dataset\n", + "validations.validate_dataset(merged_dataset)" + ] + }, + { + "cell_type": "code", + "execution_count": 13, + "id": "a311e73a-ba56-43ce-ba29-c40c1fcba43d", + "metadata": {}, + "outputs": [ + { + "name": "stdout", + "output_type": "stream", + "text": [ + "Reaction entry 21:\n" + ] + }, + { + "data": { + "text/plain": [ + "identifiers {\n", + " type: CUSTOM\n", + " details: \"Sample number\"\n", + " value: \"B5\"\n", + "}\n", + "inputs {\n", + " key: \"Reactant\"\n", + " value {\n", + " components {\n", + " identifiers {\n", + " type: SMILES\n", + " value: \"COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC\"\n", + " }\n", + " amount {\n", + " mass {\n", + " value: 1.49\n", + " units: MILLIGRAM\n", + " }\n", + " }\n", + " reaction_role: REACTANT\n", + " is_limiting: true\n", + " }\n", + " components {\n", + " identifiers {\n", + " type: NAME\n", + " value: \"acetonitrile\"\n", + " }\n", + " identifiers {\n", + " type: SMILES\n", + " details: \"NAME resolved by the PubChem API\"\n", + " value: \"CC#N\"\n", + " }\n", + " amount {\n", + " volume {\n", + " value: 150\n", + " units: MICROLITER\n", + " }\n", + " }\n", + " reaction_role: SOLVENT\n", + " preparations {\n", + " type: DRIED\n", + " details: \"dried on alumina\"\n", + " }\n", + " }\n", + " addition_order: 3\n", + " addition_speed {\n", + " type: ALL_AT_ONCE\n", + " }\n", + " addition_device {\n", + " type: PIPETTE\n", + " }\n", + " }\n", + "}\n", + "inputs {\n", + " key: \"Ligand\"\n", + " value {\n", + " components {\n", + " identifiers {\n", + " type: NAME\n", + " value: \"(R)-1,1’-binaphthyl-2,2’-diyl ethyl phosphite\"\n", + " }\n", + " identifiers {\n", + " type: SMILES\n", + " value: \"CCOP1OC2=C(C3=C(C=CC4=CC=CC=C43)O1)C5=CC=CC=C5C=C2\"\n", + " }\n", + " amount {\n", + " moles {\n", + " value: 1\n", + " units: MICROMOLE\n", + " }\n", + " }\n", + " reaction_role: REAGENT\n", + " }\n", + " addition_order: 1\n", + " addition_speed {\n", + " type: ALL_AT_ONCE\n", + " }\n", + " addition_device {\n", + " type: CUSTOM\n", + " details: \"manual weighing\"\n", + " }\n", + " }\n", + "}\n", + "inputs {\n", + " key: \"Catalysts\"\n", + " value {\n", + " components {\n", + " identifiers {\n", + " type: SMILES\n", + " value: \"C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C\"\n", + " }\n", + " identifiers {\n", + " type: NAME\n", + " value: \"(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium\"\n", + " }\n", + " identifiers {\n", + " type: IUPAC_NAME\n", + " value: \"(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)\"\n", + " }\n", + " amount {\n", + " mass {\n", + " value: 0.13\n", + " units: MILLIGRAM\n", + " }\n", + " }\n", + " reaction_role: CATALYST\n", + " preparations {\n", + " type: SYNTHESIZED\n", + " details: \"according to literature procedure\"\n", + " }\n", + " preparations {\n", + " type: CUSTOM\n", + " details: \"stored in glove box at -20 degrees Celcius\"\n", + " }\n", + " }\n", + " components {\n", + " identifiers {\n", + " type: NAME\n", + " value: \"tributylamine\"\n", + " }\n", + " identifiers {\n", + " type: SMILES\n", + " details: \"NAME resolved by the PubChem API\"\n", + " value: \"CCCCN(CCCC)CCCC\"\n", + " }\n", + " amount {\n", + " volume {\n", + " value: 4.1\n", + " units: MICROLITER\n", + " }\n", + " }\n", + " reaction_role: REAGENT\n", + " preparations {\n", + " type: DRIED\n", + " details: \"dried with calcium hydride\"\n", + " }\n", + " preparations {\n", + " type: SPARGED\n", + " details: \"sparged with N2\"\n", + " }\n", + " preparations {\n", + " type: CUSTOM\n", + " details: \"stored under N2 in a sealed vessel\"\n", + " }\n", + " }\n", + " components {\n", + " identifiers {\n", + " type: NAME\n", + " value: \"acetonitrile\"\n", + " }\n", + " identifiers {\n", + " type: SMILES\n", + " details: \"NAME resolved by the PubChem API\"\n", + " value: \"CC#N\"\n", + " }\n", + " amount {\n", + " volume {\n", + " value: 150\n", + " units: MICROLITER\n", + " }\n", + " volume_includes_solutes: true\n", + " }\n", + " reaction_role: SOLVENT\n", + " preparations {\n", + " type: DRIED\n", + " details: \"dried on alumina\"\n", + " }\n", + " }\n", + " addition_order: 2\n", + " addition_speed {\n", + " type: ALL_AT_ONCE\n", + " }\n", + " addition_device {\n", + " type: PIPETTE\n", + " }\n", + " }\n", + "}\n", + "setup {\n", + " vessel {\n", + " type: WELL_PLATE\n", + " details: \"Paradox Standard 96-Position Parallel Synthesis block\"\n", + " material {\n", + " type: GLASS\n", + " }\n", + " preparations {\n", + " type: OVEN_DRIED\n", + " details: \"150 degrees Celcius for 2 hours\"\n", + " }\n", + " attachments {\n", + " type: MAT\n", + " details: \"covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws\"\n", + " }\n", + " volume {\n", + " value: 1\n", + " units: MILLILITER\n", + " }\n", + " }\n", + " is_automated: false\n", + " environment {\n", + " type: GLOVE_BOX\n", + " details: \"moisture- and oxygen-free\"\n", + " }\n", + "}\n", + "conditions {\n", + " temperature {\n", + " control {\n", + " type: DRY_ALUMINUM_PLATE\n", + " details: \"pre-heated temperature-controlled metal block\"\n", + " }\n", + " setpoint {\n", + " value: 80\n", + " units: CELSIUS\n", + " }\n", + " }\n", + " stirring {\n", + " type: STIR_BAR\n", + " details: \"magnetic\"\n", + " }\n", + " conditions_are_dynamic: true\n", + " details: \"Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard.\"\n", + "}\n", + "notes {\n", + " is_sensitive_to_moisture: true\n", + " is_sensitive_to_oxygen: true\n", + " procedure_details: \"Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries.\"\n", + "}\n", + "workups {\n", + " type: TEMPERATURE\n", + " details: \"cool to room temperature and opened to air\"\n", + " temperature {\n", + " control {\n", + " type: AMBIENT\n", + " }\n", + " }\n", + " stirring {\n", + " type: NONE\n", + " }\n", + " is_automated: false\n", + "}\n", + "workups {\n", + " type: ADDITION\n", + " details: \"addition of internal standard\"\n", + " input {\n", + " components {\n", + " identifiers {\n", + " type: NAME\n", + " value: \"trimethoxybenzene\"\n", + " }\n", + " identifiers {\n", + " type: SMILES\n", + " details: \"NAME resolved by the PubChem API\"\n", + " value: \"COc1cccc(OC)c1OC\"\n", + " }\n", + " amount {\n", + " mass {\n", + " value: 0.19\n", + " units: MILLIGRAM\n", + " }\n", + " }\n", + " reaction_role: INTERNAL_STANDARD\n", + " }\n", + " components {\n", + " identifiers {\n", + " type: NAME\n", + " value: \"acetonitrile\"\n", + " }\n", + " identifiers {\n", + " type: SMILES\n", + " details: \"NAME resolved by the PubChem API\"\n", + " value: \"CC#N\"\n", + " }\n", + " amount {\n", + " volume {\n", + " value: 400\n", + " units: MICROLITER\n", + " }\n", + " volume_includes_solutes: true\n", + " }\n", + " reaction_role: SOLVENT\n", + " preparations {\n", + " type: DRIED\n", + " details: \"dried on alumina\"\n", + " }\n", + " }\n", + " addition_speed {\n", + " type: ALL_AT_ONCE\n", + " }\n", + " addition_device {\n", + " type: PIPETTE\n", + " }\n", + " }\n", + " stirring {\n", + " type: CUSTOM\n", + " details: \"centrifuge\"\n", + " }\n", + " is_automated: false\n", + "}\n", + "workups {\n", + " type: ALIQUOT\n", + " details: \"300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape.\"\n", + " amount {\n", + " volume {\n", + " value: 300\n", + " units: MICROLITER\n", + " }\n", + " }\n", + " is_automated: false\n", + "}\n", + "workups {\n", + " type: CUSTOM\n", + " details: \"centrifuged\"\n", + " duration {\n", + " value: 15\n", + " units: MINUTE\n", + " }\n", + " keep_phase: \"liquid\"\n", + "}\n", + "outcomes {\n", + " reaction_time {\n", + " value: 24\n", + " units: HOUR\n", + " }\n", + " products {\n", + " identifiers {\n", + " type: NAME\n", + " value: \"5\\'-6\\'-dimethoxy-6-methylidene2\\',3\\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\\'-isoindole]-3\\'-one\"\n", + " }\n", + " identifiers {\n", + " type: MOLBLOCK\n", + " details: \"Drawn with Ketcher\"\n", + " value: \"\\n Ketcher 9202412492D 1 1.00000 0.00000 0\\n\\n 26 30 0 0 0 0 999 V2000\\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\\n 3 1 2 0 0 0\\n 4 2 2 0 0 0\\n 1 5 1 0 0 0\\n 2 3 1 0 0 0\\n 5 6 2 0 0 0\\n 6 4 1 0 0 0\\n 9 7 2 0 0 0\\n 10 8 2 0 0 0\\n 7 11 1 0 0 0\\n 8 9 1 0 0 0\\n 11 12 2 0 0 0\\n 12 10 1 0 0 0\\n 5 13 1 0 0 0\\n 6 14 1 0 0 0\\n 13 15 1 0 0 0\\n 15 14 1 0 0 0\\n 2 16 1 0 0 0\\n 16 17 1 0 0 0\\n 4 18 1 0 0 0\\n 18 17 1 0 0 0\\n 16 19 2 0 0 0\\n 17 11 1 0 0 0\\n 17 20 1 0 0 0\\n 12 21 1 0 0 0\\n 21 20 1 0 0 0\\n 21 22 2 0 0 0\\n 9 23 1 0 0 0\\n 8 24 1 0 0 0\\n 23 25 1 0 0 0\\n 24 26 1 0 0 0\\nM END\\n\"\n", + " }\n", + " identifiers {\n", + " type: SMILES\n", + " details: \"Drawn with Ketcher\"\n", + " value: \"C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3\"\n", + " }\n", + " is_desired_product: true\n", + " measurements {\n", + " analysis_key: \"LC-MS\"\n", + " type: YIELD\n", + " details: \"LC-MS yield\"\n", + " uses_internal_standard: true\n", + " is_normalized: true\n", + " uses_authentic_standard: false\n", + " percentage {\n", + " value: 39\n", + " }\n", + " }\n", + " measurements {\n", + " analysis_key: \"1H-NMR\"\n", + " type: YIELD\n", + " details: \"1H-NMR yield\"\n", + " uses_internal_standard: true\n", + " is_normalized: true\n", + " uses_authentic_standard: false\n", + " percentage {\n", + " value: 40\n", + " }\n", + " }\n", + " reaction_role: PRODUCT\n", + " }\n", + " analyses {\n", + " key: \"LC-MS\"\n", + " value {\n", + " type: LCMS\n", + " details: \"Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel.\"\n", + " chmo_id: 524\n", + " is_of_isolated_species: false\n", + " instrument_manufacturer: \"Thermo Scientific\"\n", + " }\n", + " }\n", + " analyses {\n", + " key: \"1H-NMR\"\n", + " value {\n", + " type: IR\n", + " details: \"600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe\"\n", + " chmo_id: 593\n", + " is_of_isolated_species: false\n", + " instrument_manufacturer: \"Bruker\"\n", + " }\n", + " }\n", + "}\n", + "outcomes {\n", + " products {\n", + " identifiers {\n", + " type: SMILES\n", + " value: \"COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC\"\n", + " }\n", + " measurements {\n", + " analysis_key: \"LC-MS\"\n", + " type: YIELD\n", + " details: \"LC-MS yield\"\n", + " uses_internal_standard: true\n", + " is_normalized: true\n", + " uses_authentic_standard: false\n", + " percentage {\n", + " value: 12\n", + " }\n", + " }\n", + " measurements {\n", + " analysis_key: \"1H-NMR\"\n", + " type: YIELD\n", + " details: \"1H-NMR yield\"\n", + " uses_internal_standard: true\n", + " is_normalized: true\n", + " uses_authentic_standard: false\n", + " percentage {\n", + " value: 16\n", + " }\n", + " }\n", + " reaction_role: REACTANT\n", + " }\n", + " analyses {\n", + " key: \"LC-MS\"\n", + " value {\n", + " type: LCMS\n", + " details: \"Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel.\"\n", + " chmo_id: 524\n", + " is_of_isolated_species: false\n", + " instrument_manufacturer: \"Thermo Scientific\"\n", + " }\n", + " }\n", + " analyses {\n", + " key: \"1H-NMR\"\n", + " value {\n", + " type: NMR_1H\n", + " details: \"600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe\"\n", + " chmo_id: 593\n", + " is_of_isolated_species: false\n", + " instrument_manufacturer: \"Bruker\"\n", + " }\n", + " }\n", + "}\n", + "provenance {\n", + " experimenter {\n", + " name: \"Katerina Korch\"\n", + " orcid: \"0000-0002-1436-8792\"\n", + " organization: \"University of Delaware\"\n", + " }\n", + " city: \"Delaware\"\n", + " doi: \"10.1021/acs.orglett.1c02767\"\n", + " publication_url: \"https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767\"\n", + " record_created {\n", + " time {\n", + " value: \"05/12/2024, 15:29:23\"\n", + " }\n", + " person {\n", + " username: \"saratanov\"\n", + " name: \"Sara Tanovic\"\n", + " orcid: \"0000-0002-6528-7757\"\n", + " organization: \"University of Oxford\"\n", + " email: \"sara.tanovic@gtc.ox.ac.uk\"\n", + " }\n", + " }\n", + "}" + ] + }, + "execution_count": 13, + "metadata": {}, + "output_type": "execute_result" + } + ], + "source": [ + "# Inspect random reaction from this set\n", + "random_index = np.random.randint(len(merged_dataset.reactions))\n", + "print(f\"Reaction entry {random_index}:\")\n", + "merged_dataset.reactions[random_index]" + ] + }, + { + "cell_type": "code", + "execution_count": null, + "id": "58329713-b616-454e-aa92-f8d018502bf2", + "metadata": {}, + "outputs": [], + "source": [] + } + ], + "metadata": { + "kernelspec": { + "display_name": "Python 3 (ipykernel)", + "language": "python", + "name": "python3" + }, + "language_info": { + "codemirror_mode": { + "name": "ipython", + "version": 3 + }, + "file_extension": ".py", + "mimetype": "text/x-python", + "name": "python", + "nbconvert_exporter": "python", + "pygments_lexer": "ipython3", + "version": "3.12.3" + } + }, + "nbformat": 4, + "nbformat_minor": 5 +} diff --git a/examples/submissions/11_enumeration_of_template/merged_dataset.pbtxt b/examples/submissions/11_enumeration_of_template/merged_dataset.pbtxt new file mode 100644 index 000000000..d7bb8aba3 --- /dev/null +++ b/examples/submissions/11_enumeration_of_template/merged_dataset.pbtxt @@ -0,0 +1,10280 @@ +name: "Ligand screening for Aza-Heck cyclization in total synthesis of Impatien A" +description: "24 ligands are screened for the aza-Heck cyclization in a total synthesis of Impatien A." +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "Al" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Triisobutylphosphatrane" + } + identifiers { + type: SMILES + value: "CC(C)CN1CCN2CCN(CC(C)C)P1N(CC2)CC(C)C" + } + identifiers { + type: CAS_NUMBER + value: "331465-71-5" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 32.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "A2" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Tris(4-methoxyphenyl)phosphine" + } + identifiers { + type: SMILES + value: "COc1ccc(cc1)P(c2ccc(OC)cc2)c3ccc(OC)cc3" + } + identifiers { + type: CAS_NUMBER + value: "855-38-9" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "A3" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Triphenylphosphine" + } + identifiers { + type: SMILES + value: "c1ccccc1P(c2ccccc2)c3ccccc3" + } + identifiers { + type: CAS_NUMBER + value: "603-35-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "A4" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Triphenylphosphite" + } + identifiers { + type: SMILES + value: "C1=CC=C(C=C1)OP(OC2=CC=CC=C2)OC3=CC=CC=C3" + } + identifiers { + type: CAS_NUMBER + value: "101-02-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "A6" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "2,2\342\200\262-Methylenebis[(4S)-4-phenyl-2-oxazoline]" + } + identifiers { + type: SMILES + value: "C1[C@@H](N=C(O1)CC2=N[C@H](CO2)C3=CC=CC=C3)C4=CC=CC=C4" + } + identifiers { + type: CAS_NUMBER + value: "132098-59-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B1" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Tribenzylphosphine" + } + identifiers { + type: SMILES + value: "C1=CC=C(C=C1)CP(CC2=CC=CC=C2)CC3=CC=CC=C3" + } + identifiers { + type: CAS_NUMBER + value: "7650-89-7" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B2" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Bis[(2-diphenylphosphino)phenyl] ether" + } + identifiers { + type: SMILES + value: "C1=CC=C(C=C1)P(C2=CC=CC=C2)C3=CC=CC=C3OC4=CC=CC=C4P(C5=CC=CC=C5)C6=CC=CC=C6" + } + identifiers { + type: CAS_NUMBER + value: "166330-10-5" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B3" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(S)-PipPhos" + } + identifiers { + type: SMILES + value: "C1CCN(CC1)P2OC3=C(C4=CC=CC=C4C=C3)C5=C(O2)C=CC6=CC=CC=C65" + } + identifiers { + type: CAS_NUMBER + value: "284472-79-3" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 25.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B6" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(S)-4-tert-Butyl-2-[2-(diphenyl-\nphosphino)phenyl]-2-oxazoline" + } + identifiers { + type: SMILES + value: "CC(C)(C)[C@H]1COC(=N1)C2=CC=CC=C2P(C3=CC=CC=C3)C4=CC=CC=C4" + } + identifiers { + type: CAS_NUMBER + value: "148461-16-9" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "Cl" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "CyJohnPhos" + } + identifiers { + type: SMILES + value: "C1CCC(CC1)P(C2CCCCC2)C3=CC=CC=C3C4=CC=CC=C4" + } + identifiers { + type: CAS_NUMBER + value: "247940-06-3" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C2" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "CagePhos" + } + identifiers { + type: SMILES + value: "CC12COP(OC1)OC2" + } + identifiers { + type: CAS_NUMBER + value: "1449-91-8" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 31.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C3" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "P(tBu)(3,5-bisCF3Ph)2" + } + identifiers { + type: SMILES + value: "CC(C)(C)P(C1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1)C2=CC(C(F)(F)F)=CC(C(F)(F)F)=C2" + } + identifiers { + type: CAS_NUMBER + value: "1616979-85-1" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 4.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C4" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "P(p-FPh)3" + } + identifiers { + type: SMILES + value: "C1=CC(=CC=C1F)P(C2=CC=C(C=C2)F)C3=CC=C(C=C3)F" + } + identifiers { + type: CAS_NUMBER + value: "18437-78-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 5.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C6" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "BIPOL-Al (R)" + } + identifiers { + type: SMILES + value: "COC1=C(C2=CC=CC=C2C=C1)C3=C(C=CC4=CC=CC=C43)P(C5=CC=CC=C5)C6=CC=CC=C6" + } + identifiers { + type: CAS_NUMBER + value: "500103-26-4" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 11.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 8.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D1" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(R)-MOP" + } + identifiers { + type: SMILES + value: "COC1=C(C2=CC=CC=C2C=C1)C3=C(C=CC4=CC=CC=C43)P(C5=CC=CC=C5)C6=CC=CC=C6" + } + identifiers { + type: CAS_NUMBER + value: "145964-33-6" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 34.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D3" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(S)-FuP-tBu" + } + identifiers { + type: SMILES + value: "CC(C)(C)P1OC2=CC=CC3=C2C4(CC3)CCC5=C4C(=CC=C5)O1" + } + identifiers { + type: CAS_NUMBER + value: "912457-08-0" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D4" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "1,3,5,7-Tetramethy1-6-pheny1-\n2,4,8-trioxa-6-\nphosphaadamantane" + } + identifiers { + type: SMILES + value: "C[C@@]1(C2)P(C3=CC=CC=C3)[C@]4(C)O[C@@]2(C)O[C@@](C)(C4)O1" + } + identifiers { + type: CAS_NUMBER + value: "977739-46-3" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 26.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D5" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(R)-BTFM-Garphos" + } + identifiers { + type: SMILES + value: "COC1=CC(=C(C(=C1)P(C2=CC(=CC(=C2)C(F)(F)F)C(F)(F)F)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C4=C(C=C(C=C4P(C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F)C6=CC(=CC(=C6)C(F)(F)F)C(F)(F)F)OC)OC)OC" + } + identifiers { + type: CAS_NUMBER + value: "1365531-84-5" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 14.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D6" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "No ligand" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 35.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "AS" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "Tris[3,5-bis(trifluoromethyl)phenyl]phosphine" + } + identifiers { + type: SMILES + value: "C1=C(C=C(C=C1C(F)(F)F)P(C2=CC(=CC(=C2)C(F)(F)F)C(F)(F)F)C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C(F)(F)F" + } + identifiers { + type: CAS_NUMBER + value: "175136-62-6" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 10.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 7.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 17.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B4" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(3aR,8aR)-(-)-(2,2-Dimethy1-\n4,4,8,8-tetraphenyl-tetrahydro-\n[1,3]dioxolo-[4,5-e][1,3,2]-\ndioxaphosphepin-6-\ny1)dimethylamine" + } + identifiers { + type: SMILES + value: "CC1(O[C@@H]2[C@@H](O1)C(OP(OC2(C3=CC=CC=C3)C4=CC=CC=C4)N(C)C)(C5=CC=CC=C5)C6=CC=CC=C6)C" + } + identifiers { + type: CAS_NUMBER + value: "213843-90-4" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 2.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 3.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 29.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 28.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "B5" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(R)-1,1\342\200\231-binaphthyl-2,2\342\200\231-diyl ethyl phosphite" + } + identifiers { + type: SMILES + value: "CCOP1OC2=C(C3=C(C=CC4=CC=CC=C43)O1)C5=CC=CC=C5C=C2" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 39.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 40.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 12.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 16.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "C5" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "JackiePhos" + } + identifiers { + type: SMILES + value: "CC(C)C1=CC(=C(C(=C1)C(C)C)C2=C(C=CC(=C2P(C3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C4=CC(=CC(=C4)C(F)(F)F)C(F)(F)F)OC)OC)C(C)C" + } + identifiers { + type: CAS_NUMBER + value: "1160861-60-8" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 1.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 13.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 15.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} +reactions { + identifiers { + type: CUSTOM + details: "Sample number" + value: "D2" + } + inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "(R)-ShiP" + } + identifiers { + type: SMILES + value: "C1CC23CCC4=C2C(=CC=C4)OP(OC5=CC=CC1=C35)OC6=CC=CC=C6" + } + identifiers { + type: CAS_NUMBER + value: "656233-53-3" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } + } + inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + } + setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } + } + conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." + } + notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." + } + workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false + } + workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false + } + workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false + } + workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" + } + outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5\'-6\'-dimethoxy-6-methylidene2\',3\',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1\'-isoindole]-3\'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 19.0 + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 22.0 + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: 20.0 + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } + } + provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } + } +} diff --git a/examples/submissions/11_enumeration_of_template/template_nmr_v2.1.pbtxt b/examples/submissions/11_enumeration_of_template/template_nmr_v2.1.pbtxt new file mode 100644 index 000000000..d0858e24c --- /dev/null +++ b/examples/submissions/11_enumeration_of_template/template_nmr_v2.1.pbtxt @@ -0,0 +1,461 @@ +identifiers { + type: CUSTOM + details: "Sample number" + value: "$Sample$" +} +inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } +} +inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "$ligand_name$" + } + identifiers { + type: SMILES + value: "$ligand_smiles$" + } + identifiers { + type: CAS_NUMBER + value: "$ligand_cas$" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } +} +inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } +} +setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } +} +conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." +} +notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." +} +workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false +} +workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false +} +workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false +} +workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" +} +outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5'-6'-dimethoxy-6-methylidene2',3',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1'-isoindole]-3'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: $11_yield$ + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: $11_nmr_yield$ + } + } + reaction_role: PRODUCT + } + analyses { + key: "1H-NMR" + value { + type: IR + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } +} +outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: $3_yield$ + } + } + measurements { + analysis_key: "1H-NMR" + type: YIELD + details: "1H-NMR yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: $3_nmr_yield$ + } + } + reaction_role: REACTANT + } + analyses { + key: "1H-NMR" + value { + type: NMR_1H + details: "600 MHz Bruker AVANCE NMR spectrometer equipped with a Bruker SMART probe" + chmo_id: 593 + is_of_isolated_species: false + instrument_manufacturer: "Bruker" + } + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } +} +provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } +} +reaction_id: "Reaction $Entry$" diff --git a/examples/submissions/11_enumeration_of_template/template_v2.1.pbtxt b/examples/submissions/11_enumeration_of_template/template_v2.1.pbtxt new file mode 100644 index 000000000..117e2d822 --- /dev/null +++ b/examples/submissions/11_enumeration_of_template/template_v2.1.pbtxt @@ -0,0 +1,419 @@ +identifiers { + type: CUSTOM + details: "Sample number" + value: "$Sample$" +} +inputs { + key: "Catalysts" + value { + components { + identifiers { + type: SMILES + value: "C[Si](C)(C)C[Pd]345(C1=C3CCC4=C5CC1)C[Si](C)(C)C" + } + identifiers { + type: NAME + value: "(1,5-Cyclooctadiene)bis[(trimethylsilyl)methyl]palladium" + } + identifiers { + type: IUPAC_NAME + value: "(1Z,5Z)-cycloocta-1,5-diene; methanidyl(trimethyl)silane; palladium(2+)" + } + amount { + mass { + value: 0.13 + units: MILLIGRAM + } + } + reaction_role: CATALYST + preparations { + type: SYNTHESIZED + details: "according to literature procedure" + } + preparations { + type: CUSTOM + details: "stored in glove box at -20 degrees Celcius" + } + } + components { + identifiers { + type: NAME + value: "tributylamine" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CCCCN(CCCC)CCCC" + } + amount { + volume { + value: 4.1 + units: MICROLITER + } + } + reaction_role: REAGENT + preparations { + type: DRIED + details: "dried with calcium hydride" + } + preparations { + type: SPARGED + details: "sparged with N2" + } + preparations { + type: CUSTOM + details: "stored under N2 in a sealed vessel" + } + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 2 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } +} +inputs { + key: "Ligand" + value { + components { + identifiers { + type: NAME + value: "$ligand_name$" + } + identifiers { + type: SMILES + value: "$ligand_smiles$" + } + identifiers { + type: CAS_NUMBER + value: "$ligand_cas$" + } + amount { + moles { + value: 1.0 + units: MICROMOLE + } + } + reaction_role: REAGENT + } + addition_order: 1 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: CUSTOM + details: "manual weighing" + } + } +} +inputs { + key: "Reactant" + value { + components { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + amount { + mass { + value: 1.49 + units: MILLIGRAM + } + } + reaction_role: REACTANT + is_limiting: true + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 150.0 + units: MICROLITER + } + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_order: 3 + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } +} +setup { + vessel { + type: WELL_PLATE + details: "Paradox Standard 96-Position Parallel Synthesis block" + material { + type: GLASS + } + preparations { + type: OVEN_DRIED + details: "150 degrees Celcius for 2 hours" + } + attachments { + type: MAT + details: "covered in a Teflon sheet, rubber mats, and aluminium top cover affixed to bottom plate via 9 tightly tightened screws" + } + volume { + value: 1.0 + units: MILLILITER + } + } + is_automated: false + environment { + type: GLOVE_BOX + details: "moisture- and oxygen-free" + } +} +conditions { + temperature { + control { + type: DRY_ALUMINUM_PLATE + details: "pre-heated temperature-controlled metal block" + } + setpoint { + value: 80.0 + units: CELSIUS + } + } + stirring { + type: STIR_BAR + details: "magnetic" + } + conditions_are_dynamic: true + details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." +} +notes { + is_sensitive_to_moisture: true + is_sensitive_to_oxygen: true + procedure_details: "Vials containing pre-plated ligand were added to a 96-well reaction block (Paradox Standard 96-Position Parallel Synthesis block) in positions C4-9 ,D4-9, E4-9, and F4-9 and equipped with magnetic stirbars in a moisture and oxygen-free glovebox. The remainder of the plate positions were filled with empty vials to ensure a proper seal with the lid could be obtained later.(cod)Pd(CH2TMS)2 (0.13 mg, 0.33 umol, 0.10 equiv) and nBu3N (4.10 uL, 16.7 umol, 5.00 equiv) were added as a solution in MeCN (150 uL) via micropipettor to each of the 24 wells. Then hydroxamic ether 3 (1.49 mg, 3.34 umol, 1.00 equiv) was added as a solution in MeCN (150 uL) via micropipettor. The reaction block was then covered with a Teflon sheet, rubber mats, and its aluminum top cover which were all affixed to the bottom plate via 9 tightly tightened screws. The plate was placed in a pre-heated temperature-controlled metal block on a stir plate in the glovebox and stirred at 80C for 24 h. The reaction block was then removed from the glovebox, cooled to rt, and opened to air. A solution of trimethoxybenzene (0.19 mg, 1.11 umol, 0.33 equiv) in MeCN (400 uL) was added as an internal standard to each vial of the 24 vials via micropipettor. After centrifugation, a 300 uL aliquot of each crude reaction was transferred to an analysis collection plate via micropipettor. The plate was sealed with aluminum sealing tape, and centrifuged for 15 min. The reactions were analyzed and quantified by LC-MS and integrated against the trimethoxybenzene internal standard to determine the yield of product formed in each reaction and the amount of unreacted starting material remaining. Yields determined by LC-MS were also validated by quantification of the 1H NMR spectrum of the indicated entries." +} +workups { + type: TEMPERATURE + details: "cool to room temperature and opened to air" + temperature { + control { + type: AMBIENT + } + } + stirring { + type: NONE + } + is_automated: false +} +workups { + type: ADDITION + details: "addition of internal standard" + input { + components { + identifiers { + type: NAME + value: "trimethoxybenzene" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "COc1cccc(OC)c1OC" + } + amount { + mass { + value: 0.19 + units: MILLIGRAM + } + } + reaction_role: INTERNAL_STANDARD + } + components { + identifiers { + type: NAME + value: "acetonitrile" + } + identifiers { + type: SMILES + details: "NAME resolved by the PubChem API" + value: "CC#N" + } + amount { + volume { + value: 400.0 + units: MICROLITER + } + volume_includes_solutes: true + } + reaction_role: SOLVENT + preparations { + type: DRIED + details: "dried on alumina" + } + } + addition_speed { + type: ALL_AT_ONCE + } + addition_device { + type: PIPETTE + } + } + stirring { + type: CUSTOM + details: "centrifuge" + } + is_automated: false +} +workups { + type: ALIQUOT + details: "300 microliter aliquot transferred to analysis collection plate via micropipettor, and sealed with aluminium sealing tape." + amount { + volume { + value: 300.0 + units: MICROLITER + } + } + is_automated: false +} +workups { + type: CUSTOM + details: "centrifuged" + duration { + value: 15.0 + units: MINUTE + } + keep_phase: "liquid" +} +outcomes { + reaction_time { + value: 24.0 + units: HOUR + } + products { + identifiers { + type: NAME + value: "5'-6'-dimethoxy-6-methylidene2',3',6,8-tetrahydro-2H-spiro[indeno[4,5-d][1,3]dioxole-7,1'-isoindole]-3'-one" + } + identifiers { + type: MOLBLOCK + details: "Drawn with Ketcher" + value: "\n Ketcher 9202412492D 1 1.00000 0.00000 0\n\n 26 30 0 0 0 0 999 V2000\n 4.9348 -8.1751 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8016 -7.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 6.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.9348 -9.1800 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -9.6750 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -6.2501 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -6.2496 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -5.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.5652 -7.2505 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.8348 -7.2550 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7038 -7.7500 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 4.0688 -9.6800 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 5.8038 -10.6750 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 4.7759 -10.3871 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -7.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 8.3972 -8.1746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.6652 -9.1755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 7.5312 -6.6746 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 9.1043 -8.8817 0.0000 N 0 0 0 0 0 0 0 0 0 0 0 0\n 10.4450 -8.7160 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 11.1521 -9.4231 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 10.7016 -4.7500 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 12.4312 -5.7496 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0\n 9.7357 -4.4911 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 13.3971 -6.0084 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0\n 3 1 2 0 0 0\n 4 2 2 0 0 0\n 1 5 1 0 0 0\n 2 3 1 0 0 0\n 5 6 2 0 0 0\n 6 4 1 0 0 0\n 9 7 2 0 0 0\n 10 8 2 0 0 0\n 7 11 1 0 0 0\n 8 9 1 0 0 0\n 11 12 2 0 0 0\n 12 10 1 0 0 0\n 5 13 1 0 0 0\n 6 14 1 0 0 0\n 13 15 1 0 0 0\n 15 14 1 0 0 0\n 2 16 1 0 0 0\n 16 17 1 0 0 0\n 4 18 1 0 0 0\n 18 17 1 0 0 0\n 16 19 2 0 0 0\n 17 11 1 0 0 0\n 17 20 1 0 0 0\n 12 21 1 0 0 0\n 21 20 1 0 0 0\n 21 22 2 0 0 0\n 9 23 1 0 0 0\n 8 24 1 0 0 0\n 23 25 1 0 0 0\n 24 26 1 0 0 0\nM END\n" + } + identifiers { + type: SMILES + details: "Drawn with Ketcher" + value: "C=C1c2ccc3c(c2CC12NC(=O)c1cc(OC)c(OC)cc12)OCO3" + } + is_desired_product: true + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: $11_yield$ + } + } + reaction_role: PRODUCT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } +} +outcomes { + products { + identifiers { + type: SMILES + value: "COc1cc(C(=O)NOc2ccccc2)c(C2=C(C)c3ccc4c(c3C2)OCO4)cc1OC" + } + measurements { + analysis_key: "LC-MS" + type: YIELD + details: "LC-MS yield" + uses_internal_standard: true + is_normalized: true + uses_authentic_standard: false + percentage { + value: $3_yield$ + } + } + reaction_role: REACTANT + } + analyses { + key: "LC-MS" + value { + type: LCMS + details: "Thermo Q-Exactive Orbitrap using electrospray ionization (ESI). Column chromatography was performed either by hand or by use of Isolera 3 Biotage unit with 40-63um silica gel." + chmo_id: 524 + is_of_isolated_species: false + instrument_manufacturer: "Thermo Scientific" + } + } +} +provenance { + experimenter { + name: "Katerina Korch" + orcid: "0000-0002-1436-8792" + organization: "University of Delaware" + } + city: "Delaware" + doi: "10.1021/acs.orglett.1c02767" + publication_url: "https://pubs.acs.org/doi/10.1021/acs.orglett.1c02767" + record_created { + time { + value: "05/12/2024, 15:29:23" + } + person { + username: "saratanov" + name: "Sara Tanovic" + orcid: "0000-0002-6528-7757" + organization: "University of Oxford" + email: "sara.tanovic@gtc.ox.ac.uk" + } + } +} +reaction_id: "Reaction $Entry$" From af555c22bfa328b4e0b03aaa9964056d2b510fd5 Mon Sep 17 00:00:00 2001 From: Ben Deadman Date: Mon, 20 Jan 2025 16:52:27 +1300 Subject: [PATCH 7/7] Added write to ord pb.gz file Write the resulting dataset to a pb.gz file with the assinged ord id. 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a/examples/submissions/11_enumeration_of_template/template_v2.1.pbtxt b/examples/submissions/11_enumeration_of_template/template_v2.1.pbtxt index 117e2d822..0af93b200 100644 --- a/examples/submissions/11_enumeration_of_template/template_v2.1.pbtxt +++ b/examples/submissions/11_enumeration_of_template/template_v2.1.pbtxt @@ -220,7 +220,7 @@ conditions { type: STIR_BAR details: "magnetic" } - conditions_are_dynamic: true + conditions_are_dynamic: false details: "Reaction stirred at 80 degrees Celcius for 24 hours, then cooled to room temperature and opened to air before adding the internal standard." } notes {