Buchwald–Hartwig amination: 5-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile → 7-(Cyclopropylamino)-5-[6-(hydroxymethyl)indol-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile
48% 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 | 6-Hydroxymethylindole | C₉H₉NO | |
| 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 | 7-(Cyclopropylamino)-5-[6-(hydroxymethyl)indol-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile | C₁₉H₁₆N₆O | 47.5% |
Conditions
- Temperature
- 150 °C
Yield
- 48% of 7-(Cyclopropylamino)-5-[6-(hydroxymethyl)indol-1-yl]pyrazolo[1,5-a]pyrimidine-3-carbonitrile.
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%
- 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 a 40mL vial (t=g) was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (50 mg, 0.21 mmol), [Reactants], and cesium carbonate (77 mg, 0.24 mmol) in DMA (0.5 mL) ([VOLUME]),Pd2(dba)3 (9.80 mg, 10.70 µmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (12.38 mg, 0.02 mmol) were added. to give a brown suspension. The vial was filled with N2, 150C microwave for 30 min. LCMS showed completion. added MeOH (3 mL), filtered through celite. concentrated. The residue was purified by ISCO (Hexane to EtOAc:Hex=1;1 to EtOAc) to give about 34 mg offwhite solid
The source
This record comes from experimental reaction archive (ord-e0d4157f08c0492097a16f50798a4aa4). Open the source and check it against what is on this page.
experimental reaction archive record ord-e0d4157f08c0492097a16f50798a4aa4 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.
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