Buchwald–Hartwig amination: N-(5-amino-4-fluoro-2-methylphenyl)acetamide → N-[5-[[3-cyano-7-(cyclobutylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-4-fluoro-2-methylphenyl]acetamide
6% yield, run at 150 °C, as recorded by experimental reaction archive. The written procedure is below.
The atoms, from reactants to products
What was in the flask
| Role | Species | Formula | Yield |
|---|---|---|---|
| Reactant | N#Cc1cnn2c(NC3CCC3)cc(Cl)nc12 | C₁₁H₁₀ClN₅ | |
| Reactant | N-(5-amino-4-fluoro-2-methylphenyl)acetamide | C₉H₁₁FN₂O | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine) | C₃₉H₃₂OP₂ | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | Dimethylacetamide | C₄H₉NO | |
| Product | N-[5-[[3-cyano-7-(cyclobutylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-4-fluoro-2-methylphenyl]acetamide | C₂₀H₂₀FN₇O | 5.51% |
Conditions
- Temperature
- 150 °C
Yield
- 6% of N-[5-[[3-cyano-7-(cyclobutylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-4-fluoro-2-methylphenyl]acetamide.
Other recorded runs with the same starting material
No other run in the library makes this product. These runs of the same class start from one of the same reactants, which is the nearest company this record has.
Procedure
Copied from the source record, unedited
5-chloro-7-(cyclobutylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (80 mg, 0.32 mmol), N-(5-amino-4-fluoro-2-methylphenyl)acetamide (58.8 mg, 0.32 mmol), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (18.69 mg, 0.03 mmol) in DMA (5 mL) were added to a microwave tube. Pd2(dba)3 (14.79 mg, 0.02 mmol) and cesium carbonate (210 mg, 0.65 mmol) were added. The solution was degassed, filled with N2, capped, then microwaved at 150C for 30 min. The organic solvent was removed. TLC showed two closely associated peaks, so product was purified via Gilson. Appropriate fractions were collected, concentrated by rotovap, and dried in the oven overnight. LCMS, HPLC, and NMR revealed desired product. See attachments.
The source
This record comes from experimental reaction archive (ord-b55c5711f803482494d33a05fbba3389). Open the source and check it against what is on this page.
experimental reaction archive record ord-b55c5711f803482494d33a05fbba3389 from dataset "750 AstraZeneca ELN dataset" (url: https://chemrxiv.org/engage/chemrxiv/article-details/60c9e3f37792a23bfdb2d471). No atom mapping is provided by the source.
How to read this record
This is one experiment, not a rule. It says that on one occasion these species were combined under these conditions and this came out. It does not say the reaction will give the same result on your substrate, and nothing on the page has been generalised into a claim that it would.
The pathway is a separate question, kept on separate pages. A mechanism here is the canonical arrow pushing for a class, run on real structures and labelled rule-derived. It is not evidence, and this record is not a mechanism.
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