Buchwald–Hartwig amination: 5-Chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile → Acetamide, N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-[[2-(dimethylamino)ethyl]methylamino]phenyl]-
16% 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 | N-[5-amino-2-[2-(dimethylamino)ethyl-methylamino]phenyl]acetamide | C₁₃H₂₂N₄O | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane | C₂₉H₄₅P | |
| Catalyst | Bis(dibenzylideneacetone)palladium | C₅₁H₄₂O₃Pd₂ | |
| Solvent | 1,4-Dioxane | C₄H₈O₂ | |
| Product | Acetamide, N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-[[2-(dimethylamino)ethyl]methylamino]phenyl]- | C₂₃H₂₉N₉O | 15.62% |
Conditions
- Temperature
- 150 °C
Yield
- 16% of Acetamide, N-[5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]-2-[[2-(dimethylamino)ethyl]methylamino]phenyl]-.
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 | — | 29% |
| Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphane; Bis(dibenzylideneacetone)palladium | Cesium carbonate | 1,4-Dioxane | 150 °C | — | 16% (this run) |
Procedure
Copied from the source record, unedited
Two reactions setup, each 600 mg scale. A 20 mL microwave reactor vial was charged with 5-chloro-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidine-3-carbonitrile (1.2 g, 5.14 mmol), N-(5-amino-2-((2-(dimethylamino)ethyl)(methyl)amino)phenyl)acetamide (1.414 g, 5.65 mmol), 2-Di-t-butylphosphino-2',4',6'-tri-i-propyl-1,1'-biphenyl (0.218 g, 0.51 mmol), Pd2dba3 (0.235 g, 0.26 mmol) and CS2CO3 (5.02 g, 15.41 mmol). The vessel was fitted with a septum and gas inlet and dioxane (20 mL) was added via syringe. The resulting suspension was stirred for 5 min under nitrogen. The septum and gas inlet was quickly replaced with a microwave vial cap and the mixture was heated at 150 degrees under microwave irradiation for 1h. Two reactions combined and filtered through celite. The filtrate concentrated and
The source
This record comes from experimental reaction archive (ord-5410161a80384996abaacdd18920aec7). Open the source and check it against what is on this page.
experimental reaction archive record ord-5410161a80384996abaacdd18920aec7 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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