Buchwald–Hartwig amination: 3-(2,5-Dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine → 2-[4-[4-[(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-3-methoxyphenyl]piperazin-1-yl]ethanol
11% yield, run at 140 °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 | 3-(2,5-Dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine | C₁₁H₆Cl₂N₄ | |
| Reactant | 2-(4-(4-Amino-3-methoxyphenyl)piperazin-1-yl)ethanol | C₁₃H₂₁N₃O₂ | |
| Reagent | Cesium carbonate | CCs₂O₃ | |
| Catalyst | (R)-(-)-1-[(S)-2-(Dicyclohexylphosphino)ferrocenyl]ethyldi-t-butylphosphine;Ferrocene, 1-[(1R)-1-[bis(1,1-dimethylethyl)phosphino]ethyl]-2-(dicyclohexylphosphino)-, (2R)- | C₃₂H₆₂FeP₂ | |
| Catalyst | Palladium (II) acetate | C₄H₈O₄Pd | |
| Solvent | 1,2-Dimethoxyethane | C₄H₁₀O₂ | |
| Product | 2-[4-[4-[(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-3-methoxyphenyl]piperazin-1-yl]ethanol | C₂₄H₂₆ClN₇O₂ | 11.05% |
Conditions
- Temperature
- 140 °C
Yield
- 11% of 2-[4-[4-[(5-Chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-3-methoxyphenyl]piperazin-1-yl]ethanol.
Procedure
Copied from the source record, unedited
3-(2,5-dichloropyrimidin-4-yl)pyrazolo[1,5-a]pyridine (200 mg, 0.75 mmol), 2-(4-(4-amino-3-methoxyphenyl)piperazin-1-yl)ethanol (190 mg, 0.75 mmol), cesium carbonate (295 mg, 0.91 mmol), diacetoxypalladium (13.55 mg, 0.06 mmol) and (R)-(-)-1-[(S)-2-(DICYCLOHEXYLPHOSPHINO)FERROCENYL]ETHYLDI-T- BUTYLPHOSPHINE (41.8 mg, 0.08 mmol) were suspended in DME (5 mL) and sealed into a microwave tube. The reaction was degased, purged with nitrogen and heated to 140 °C over a period of 30 minutes in the microwave reactor. The reaction mixture was filtratet and the fitrate was evaporated. The crude product was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in dichloromethane. The solvent was evaporated to dryness to afford 2-(4-(4-(5-chloro-4-(pyrazolo[1,5-a]pyridin-3-yl)p
The source
This record comes from experimental reaction archive (ord-b16c1805f7d5406ba2f0d69bfae1736b). Open the source and check it against what is on this page.
experimental reaction archive record ord-b16c1805f7d5406ba2f0d69bfae1736b 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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