Buchwald–Hartwig amination: 5-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile → N-[1-[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]indol-6-yl]-N-methylacetamide
16% 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 | N-(1H-indol-6-yl)-N-methylacetamide | C₁₁H₁₂N₂O | |
| 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-[1-[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]indol-6-yl]-N-methylacetamide | C₂₁H₁₉N₇O | 15.88% |
Conditions
- Temperature
- 150 °C
Yield
- 16% of N-[1-[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]indol-6-yl]-N-methylacetamide.
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-[3-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamide67%
- 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-[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, added 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (84mg), N-(1H-indol-6-yl)-N-methylacetamide (67 mg), Pd2(dba)3 (16 mg), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (20mg) cesium carbonate(129 mg) in anhydrous DMA (0.5mL). under microwave 150C for 30 min. the mixture was filtered. washed with MeOH. combinde organic solvent, dried to dryness. The residue solid was washed with MeOH to give about 22mg offwhite solid (product.
The source
This record comes from experimental reaction archive (ord-2f0f980a972d4857b85fb2314cbcce6e). Open the source and check it against what is on this page.
experimental reaction archive record ord-2f0f980a972d4857b85fb2314cbcce6e 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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