Reaction screening in multiwell plates: high-throughput optimization of a Buchwald–Hartwig amination

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    "slug": "ord-cook-2021-buchwald-hartwig-96-well",
    "title": "Reaction screening in multiwell plates: high-throughput optimization of a Buchwald–Hartwig amination",
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    "campaign": "open-reaction-database-wishlist",
    "summary": "Curate this paper's reaction data into a validated Open Reaction Database dataset. Nature Protocols 2021, DOI 10.1038/s41596-020-00452-7. Source data: tables in the Supporting Information PDF."
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    "created_at": "2026-10-14T19:42:49Z",
    "changelog_md": "Add pinned automatic ORD validation, two independent model-qualified agent reviews, and authorized curator provenance guidance. Existing Attempts retain their original revision.",
    "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:** Reaction screening in multiwell plates: high-throughput optimization of a Buchwald–Hartwig amination\n- **Authors:** Adam Cook, Roxanne Clément, Stephen G. Newman\n- **Published:** Nature Protocols, 2021-01-11\n- **DOI:** [10.1038/s41596-020-00452-7](https://doi.org/10.1038/s41596-020-00452-7)\n- **ORD wishlist card:** [open on GitHub](https://github.com/orgs/open-reaction-database/projects/11?pane=issue&itemId=126570075)\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: 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\nData source: the Supplementary Information PDF on nature.com (open download, about 1.5 MB). Supporting Table 1 lists GC yields for all 96 wells (A1-H12) of three replicate plates (A, B, C). Yields come from a 5-point calibration against 1,3,5-trimethoxybenzene as internal standard. Reaction: [Pd(cinnamyl)Cl]2-catalysed N-arylation of 2-pyrrolidone with 2-chloro- or 2-bromopyrimidine in toluene at 100 °C for 16 h. Variables are 12 ligands (RuPhos, Xantphos, DPEPhos, IPr, PCy3, dppf, BINAP, dcype, DavePhos, tBuXPhos, SPhos, P(o-tolyl)3) and 4 bases (NaOtBu, Cs2CO3, KHMDS, DBU). The well-to-condition map is in article Fig. 7. Check it against the ligand, base and halide averages in SI Figs. 9-12. Plates A and B used a hotplate and gravity filtration. Plate C used a tumble stirrer and pressurised filtration, so record the equipment per plate. The source has no SMILES. All components are common commercial reagents and can be resolved by name. A 1 mmol round-bottom-flask scale-up (71% isolated yield) can be included as one extra reaction.\n\nKnown locations:\n\n- [https://www.nature.com/articles/s41596-020-00452-7](https://www.nature.com/articles/s41596-020-00452-7): Article landing page (Nat Protoc 2021, 16, 1152). The article is closed access. Figure captions are visible, including Fig. 7, the 96-well dosing layout (plate map). (license: closed article (Springer Nature TDM licence only))\n- [https://media.springernature.com/original/springer-static/esm/art%3A10.1038%2Fs41596-020-00452-7/MediaObjects/41596_2020_452_MOESM1_ESM.pdf](https://media.springernature.com/original/springer-static/esm/art%3A10.1038%2Fs41596-020-00452-7/MediaObjects/41596_2020_452_MOESM1_ESM.pdf): Supplementary Information PDF (~1.5 MB). Contains the procedure, ligand structures (SI Fig. 1), plate yield heatmaps (SI Figs. 3-5), Supporting Table 1 with yields per well for plates A/B/C plus standard deviations, per-ligand/base/halide averages (SI Figs. 9-12), and a 1 mmol scale-up with 71%… (license: publisher SI, no open licence stated)\n- [https://www.nature.com/articles/s41596-020-00452-7/figures/7](https://www.nature.com/articles/s41596-020-00452-7/figures/7): Fig. 7, the plate dosing layout (which ligand, base and halopyrimidine is in each well). Needed to map wells to conditions. (license: closed article figure)\n- [https://media.springernature.com/original/springer-static/esm/art%3A10.1038%2Fs41596-020-00452-7/MediaObjects/41596_2020_452_MOESM2_ESM.pdf](https://media.springernature.com/original/springer-static/esm/art%3A10.1038%2Fs41596-020-00452-7/MediaObjects/41596_2020_452_MOESM2_ESM.pdf): Reporting Summary PDF (~120 KB). No reaction data. (license: publisher SI)\n\n## Pitfalls\n\nEach well was run in triplicate on separate plates. Recommended: one Reaction per well per plate (288 reactions), not averaged outcomes. The plate map comes from a closed-access figure, so check it against the SI summary averages. Some wells report 0% yield. Plate C used different stirring/filtration hardware. Outcomes are GC calibrated yields, not isolated yields.\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. 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