Buchwald–Hartwig amination: 5-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile → N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-(4-methylpiperazin-1-yl)phenyl]acetamide
33% 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-[5-amino-2-(4-methylpiperazin-1-yl)phenyl]acetamide | C₁₃H₂₀N₄O | |
| 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-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-(4-methylpiperazin-1-yl)phenyl]acetamide | C₂₃H₂₇N₉O | 32.78% |
Conditions
- Temperature
- 150 °C
Yield
- 33% of N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-(4-methylpiperazin-1-yl)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-[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%
- 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 (80 mg, 0.34 mmol), [Reactants], and cesium carbonate (145 mg, 0.45 mmol) in DMA (0.5 mL) ([VOLUME]),Pd2(dba)3 (15.68 mg, 0.02 mmol) and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (19.81 mg, 0.03 mmol) were added. to give a brown suspension. The vial was filled with N2, 150C microwave for 30 min. LCMS showed completion. concentrated. loaded on ISCO (Hex to Hex:EtOAc To EtOAc:MeOH=10:1 to EtOAc:MeOH:Et3N=10:1:0.1) to give yellow solid. This yellow solid was washed with EtOAc(1mL) to give 40mg pure compound. NMR, 1H,HPLC are OK, see attachment
The source
This record comes from experimental reaction archive (ord-a86dba2ccd9142e390883516f628700c). Open the source and check it against what is on this page.
experimental reaction archive record ord-a86dba2ccd9142e390883516f628700c 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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