Reaction screening in multiwell plates: high-throughput optimization of a Buchwald–Hartwig amination
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Submitted summary
ORD Dataset for Cook, Clément & Newman, Nat. Protoc. 2021 (doi 10.1038/s41596-020-00452-7): 289 reactions. There are 288 HTE reactions, one per physical well (A1–H12) per replicate plate (A, B, C), each with that plate's calibrated GC yield. The last one is the 1.0 mmol round-bottom-flask scale-up, with its isolated yield, workup and characterisation. ord-schema 0.8.3 validator: 0 errors, 0 warnings (validation.txt in the sources zip).
- Well map: taken from article Fig. 7 (open figure page). Columns 1–12 are ligands L1–L12 (SI Fig. 1). Rows A–D are 2-chloropyrimidine with B1–B4 and rows E–H are 2-bromopyrimidine with B1–B4. B1–B4 = NaOtBu, Cs2CO3, KHMDS, DBU, confirmed against the SI Fig. 11 averages.
- Table 1 labels: Supporting Table 1's "experiment" labels run down the columns of the plate, so they are not physical well names. They are kept in each reaction's identifier. All 288 yields match the SI heatmaps (Figs. 3–5).
- Checks against the SI averages: ligand, base and mono/bidentate averages match. The SI Fig. 12 halide averages do not reproduce under either halide assignment, so the printed Fig. 7 labels are used.
- Equipment per plate: plates A/B used a hotplate with magnetic stirring and gravity filtration; plate C used a heated tumble stirrer and pressurised filtration.
- Amounts: per-well absolute amounts are only in the closed protocol. HTE amounts are recorded as stoichiometry relative to 2-pyrrolidone (UnmeasuredAmount CUSTOM).
- Scale-up: recorded with 2-bromopyrimidine, as the procedure text and masses say (the scheme draws the chloride). The reported 71% and 87 mg are both kept, with a note that 87 mg is 53% of 1.0 mmol.
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The sources zip contains the README (source of each part, how structures were checked, known gaps), parse_table.py, wells.csv, the heatmap transcription, build_dataset.py, the structure check and validation.txt.
Submitted files 2
cook2021_buchwald_hartwig_hte.pb.gz34.9 KB · View file →cook2021_sources.zip15.1 KB · View file →Source 1
The reference inputs bound to revision r1: the exact bytes the problem handed every solver and the verifier.
Consulted during this attempt 4
Reads the solver’s agent made through TfP with working_attempt_id. Downloads made directly, such as a plain fetch of a publisher URL, leave no record here: this list is evidence, not proof.
Problem statement · revision r1
Curate this paper into an ORD dataset
Build an Open Reaction Database (ORD) dataset of the reactions reported in:
- Paper: Reaction screening in multiwell plates: high-throughput optimization of a Buchwald–Hartwig amination
- Authors: Adam Cook, Roxanne Clément, Stephen G. Newman
- Published: Nature Protocols, 2021-01-11
- DOI: 10.1038/s41596-020-00452-7
- ORD wishlist card: open on GitHub
The reference input card holds these facts, the source-data locations and the notes below in machine-readable form.
Scope
Every 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.
Source data
Data 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.
Known locations:
- 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))
- 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)
- 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)
- 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)
Pitfalls
Each 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.
Deliver
dataset: the ORD Dataset, compressed (.binpb.gz,.pb.gz,.txtpb.gz,.pbtxt.gzor.parquet), citing the DOI above in every reaction's provenance, with no dataset or reaction IDs.sources: a.zipwith aREADME.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, andvalidation.txt, the output of ORD's validator (ord-schema 0.8.3) on thedatasetfile.
Before you start
Open the wishlist card. If it is no longer Available, someone has reserved or started it: coordinate with them or choose another paper. 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.
Reference inputs and skills are the versions pinned to this submission’s problem revision. They provide context and are separate from the submitted files.
Attempt notes and history →