反应详情

温度

140 °C

A 20-mL microwave vial was charged with ethyl 5-chloropyrazolo[1,5-a]pyrimidine-3-carboxylate (1.28 g, 5.67 mmol, 1 equiv), 2-amino-6-(trifluoromethyl)pyridine (1.10 g, 6.81 mmol, 1.2 equiv), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (132 mg, 0.22 mmol, 4 mol %), tris(dibenzylideneacetone) dipalladium(0) (104 mg, 0.11 mmol, 2 mol %), sodium tert-butoxide (652 mg, 6.81 mmol, 1.2 equiv) and toluene (12 mL). The vial was sealed and the contents degassed, purged with argon and then heated in a microwave reactor at 140° C. for 20 minutes. After cooling, the mixture was diluted with ethyl acetate and filtered through a pad of Celite®. The filtrate was washed with water and saturated aqueous sodium chloride solution, dried over anydrous sodium sulphate, filtered, and concentrated under vacuum. The resultant residue was purified by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in dichloromethane) to give 344 mg (17%) of ethyl 5-(6-(trifluoromethyl)pyridin-2-ylamino)pyrazolo[1,5-a]pyrimidine-3-carboxylate as an orange solid. LCMS (ESI) m+H=352.1; 1H NMR (300 MHz, DMSO-d6) δ: 11.06 (s, 1H), 9.16 (d, 1H), 8.94 (d, 1H), 8.39 (s, 1H), 8.10 (t, 1H), 7.57 (d, 1H), 7.05 (d, 1H), 4.31 (q, 2H), 1.40 (t, 3H).

1. customThe vial was sealed
2. customthe contents degassed
3. custompurged with argon
4. temperatureAfter cooling
5. additionthe mixture was diluted with ethyl acetate
6. filtrationfiltered through a pad of Celite®
7. washThe filtrate was washed with water and saturated aqueous sodium chloride solution
8. dry with materialdried over anydrous sodium sulphate
9. filtrationfiltered
10. concentrationconcentrated under vacuum
11. customThe resultant residue was purified by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in dichloromethane)