Buchwald–Hartwig amination: 5-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile → N-[3-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamide
67% 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 | 5-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile | C₁₀H₈ClN₅ | |
| Reactant | m-Aminoacetanilide | C₈H₁₀N₂O | |
| 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-[3-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamide | C₁₈H₁₇N₇O | 67.26% |
Conditions
- Temperature
- 150 °C
Yield
- 67% of N-[3-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]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.
- N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-[2-hydroxyethyl(methyl)amino]phenyl]acetamide51%
- 7-(Cyclopropylamino)-5-[6-(hydroxymethyl)indol-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile48%
- N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]phenyl]acetamide37%
- 5-[4-Chloro-3-(methylsulfonylmethyl)anilino]-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile35%
- N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-(4-methylpiperazin-1-yl)phenyl]acetamide33%
- Acetamide, N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-[[2-(dimethylamino)ethyl]methylamino]phenyl]-29%
- N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-[3-(dimethylamino)propyl-methylamino]phenyl]acetamide29%
- N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-methylphenyl]acetamide23%
- N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-4-fluoro-2-methylphenyl]acetamide21%
- N-[1-[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]indol-6-yl]-N-methylacetamide16%
- N-[2-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-5-methyl-4-pyridinyl]acetamide11%
- N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-propan-2-ylphenyl]acetamide10%
Procedure
Copied from the source record, unedited
in microwave tube was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (80 mg, 0.34 mmol), N-(3-aminophenyl)acetamide (51.4 mg, 0.34 mmol), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (19.81 mg, 0.03 mmol) in DMA (0.5 mL).Pd2(dba)3 (15.68 mg, 0.02 mmol) and cesium carbonate (123 mg, 0.38 mmol) were added. degassed, filled with N2.capped. then microwave 150C for 30 min. added 2 mL of MeOH, filtered through celite. concentrated. The residue was purified by ISCO (Hex to Hex:EtOAc=1:4 to 1:1 to EtOAc), collected prod fractions. concentrated to brown semi-solid
The source
This record comes from experimental reaction archive (ord-6d8aa98c735648d3b6dca8975bbef9d2). Open the source and check it against what is on this page.
experimental reaction archive record ord-6d8aa98c735648d3b6dca8975bbef9d2 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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