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-methylphenyl]acetamide
23% yield, run at 150 °C, as recorded by experimental reaction archive. The written procedure is below. One of 2 recorded runs making this product; all of them are compared 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 | 2-Acetylamino-4-aminotoluene | C₉H₁₂N₂O | |
| 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-methylphenyl]acetamide | C₁₉H₁₉N₇O | 22.63% |
Conditions
- Temperature
- 150 °C
Yield
- 23% of N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-methylphenyl]acetamide.
Every recorded run making this product
2 runs of this class made the same product and differed in what else was in the flask. They are listed from the highest yield down, with this page's run marked.
| Catalyst | Reagents | Solvent | Temp. | Time | Yield |
|---|---|---|---|---|---|
| 1,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine); Bis(dibenzylideneacetone)palladium | Cesium carbonate | Dimethylacetamide | 150 °C | — | 23% (this run) |
| 2-(Dicyclohexylphosphino)biphenyl; Bis(dibenzylideneacetone)palladium | sodium 2-methylpropan-2-olate | Dimethylacetamide | 120 °C | — | 0% |
Procedure
Copied from the source record, unedited
in microwave tube was 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (500 mg, 2.14 mmol), N-(5-amino-2-methylphenyl)acetamide (351 mg, 2.14 mmol), and (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (124 mg, 0.21 mmol) in DMA (2.5 mL).Pd2(dba)3 (98 mg, 0.11 mmol) and cesium carbonate (1394 mg, 4.28 mmol) were added. degassed, filled with N2.capped. then microwave 150C for 30 min. The reaction was divided by 5, run 100mg scale five time. combined all of crude mixture, filtered and washed with MeOH. the organic solvent was removed. The black residue was tried to purifed by ISCO.(40g cloumn, Hex to EtOAc:Hex =1:1 to EtOAc), colleceted product fraction. concentrated to give offwhite solid. LCMS showed about 10% impurity. The solid was washed with hot EtOAc
The source
This record comes from experimental reaction archive (ord-9f120d17ec3047d5829b45c5b320d657). Open the source and check it against what is on this page.
experimental reaction archive record ord-9f120d17ec3047d5829b45c5b320d657 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.
Where to next
More Buchwald–Hartwig amination records
Other runs of this class, one page per distinct transformation.
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