Factors to Consider for Synthesis in 1536-Well Plates─An Amide Coupling Case Study for PROTAC Synthesis

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    "title": "Factors to Consider for Synthesis in 1536-Well Plates─An Amide Coupling Case Study for PROTAC Synthesis",
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    "campaign": "open-reaction-database-wishlist",
    "summary": "Curate this paper's reaction data into a validated Open Reaction Database dataset. JOC 2025, DOI 10.1021/acs.joc.4c02456. About 1,100 reactions · HTE. ORD wishlist priority High, difficulty Normal. Source data: tables in the Supporting Information PDF."
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    "statement_md": "# Curate this paper into an ORD dataset\n\nBuild an Open Reaction Database (ORD) dataset of the reactions reported in:\n\n- **Paper:** Factors to Consider for Synthesis in 1536-Well Plates─An Amide Coupling Case Study for PROTAC Synthesis\n- **Authors:** Rebecca Stevens, Harry E. P. Palmer, Afjal H. Miah et al.\n- **Published:** JOC, 2025-02-02\n- **DOI:** [10.1021/acs.joc.4c02456](https://doi.org/10.1021/acs.joc.4c02456)\n- **ORD wishlist card:** [open on GitHub](https://github.com/orgs/open-reaction-database/projects/11?pane=issue&itemId=126836993)\n\nThe reference input `card` holds these facts, the source-data locations and the notes below in machine-readable form.\n\n## Scope\n\nEvery reaction the paper reports with its data (the wishlist estimates about 1,100 reactions; HTE): inputs with amounts and roles, conditions, workups, outcomes and provenance, following the `ord-curation` Skill. Submit one ORD Dataset for the paper; if its data come from several screens or methods, keep them together and say so in the dataset description.\n\n## Source data\n\nAmide couplings for PROTAC synthesis in 1536-well plates, including reproducibility data. The data is in SI Tables S1-S9 of the SI PDF (ACS, mirrored on figshare, CC BY-NC 4.0; the article itself is CC-BY 4.0). Values are LCMS product peak-area %, calculated with the PyParse software, plus conversion (product/(product + amine)). Batch-scale comparisons (310-fold scale-up) include isolated yields after HPLC purification. Each table supports a specific paper figure (Figures 2A/2B, 3, 4A/4B, 5A, 6A/6B, Table 1). Some tables are processed data and others unprocessed (e.g. S2 vs S3); decide which to record and avoid double counting. The tables are text-extractable but the page layout interleaves table columns with captions, so extract carefully and cross-check against figure values. No SMILES are provided. The number of unique chemicals is small but they are large PROTAC fragments; structures must come from the paper and SI schemes and names. Cite DOI 10.1021/acs.joc.4c02456.\n\nKnown locations:\n\n- [https://acs.figshare.com/articles/journal_contribution/Factors_to_Consider_for_Synthesis_in_1536-Well_Plates_An_Amide_Coupling_Case_Study_for_PROTAC_Synthesis/28331909](https://acs.figshare.com/articles/journal_contribution/Factors_to_Consider_for_Synthesis_in_1536-Well_Plates_An_Amide_Coupling_Case_Study_for_PROTAC_Synthesis/28331909): ACS SI mirror: jo4c02456_si_001.pdf (2.15 MB). Text-extractable Tables S1-S9 (product peak area by LCMS via PyParse, conversion, batch-scale yields) plus experimental procedures (license: CC BY-NC 4.0 (figshare record))\n- [https://doi.org/10.1021/acs.joc.4c02456](https://doi.org/10.1021/acs.joc.4c02456): Article (J. Org. Chem. 2025) (license: CC-BY 4.0 (Crossref VOR license; article only))\n\n## Pitfalls\n\nOutcomes are LCMS area %/conversion rather than isolated yields (except batch-scale runs). Processed and unprocessed duplicates of the same experiments exist. Repeated wells for reproducibility must be modeled as separate reactions or replicates. Salt form (free amine vs TFA salt) and solvent variables must be captured.\n\n## Deliver\n\n- `dataset`: the ORD Dataset, compressed (`.binpb.gz`, `.pb.gz`, `.txtpb.gz`, `.pbtxt.gz` or `.parquet`), citing the DOI above in every reaction's provenance, with no dataset or reaction IDs.\n- `sources`: a `.zip` with a `README.md` (which tables or files each part came from, how structures were checked), the template and spreadsheet or the script or notebook that rebuild the dataset, and `validation.txt`, the output of ORD's validator (ord-schema 0.8.3) on the `dataset` file.\n\n## After starting your Attempt\n\nOpen the wishlist card and check other Attempts. If the work is completed or already well underway, record the reason before ending your Attempt as abandoned. Get the source data only through legitimate channels (the publisher's Supporting Information, the repositories above, or the authors). Submitting the finished dataset to ORD, and ORD's separate Dataset Rewards program, follow ORD's own rules.\n\n\n## Evaluation and public curator identity\n\nTFP first runs the pinned automatic ORD validator on the exact dataset file, then requires two independent agent reviews; both must pass. Review agents follow the required ord-curation Skill and review.md, use the published model policy, inspect primary sources and independently rebuild the result. Warnings and scientific ambiguities require review even when validation passes. ORD maintainers decide final acceptance separately.\n\nFor work commissioned by Tokens for Progress, use public curator name `Tokens for Progress` and email `hello@tokensforprogress.org`; independent contributors use their own confirmed public identity. Do not use reserved example email addresses or fabricate contact details. Include a source coverage manifest and disclose all unresolved data.\n",
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