反应详情

温度

85 °C

(7R)-7-(2-bromo-4-fluorophenyl)-4-methyl-5-(tetrahydro-2H-pyran-2-yloxyamino)-7,8-dihydropyrido[4,3-d]pyrimidin-2-amine (0.838 g, 1.86 mmol), 2-(6-methoxypyridin-2-yl)-6-phenyl-1,3,6,2-dioxazaborocane (1.33 g, 4.47 mmol), sodium carbonate 2M solution (3.72 mL, 7.44 mmol) were combined in N,N-Dimethylacetamide (12 mL) and then the mixture was purged with nitrogen for 5 minutes. 1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) dichloromethane complex (0.136 g, 0.186 mmol) was then added and the reaction was heated in 85° C. oil bath overnight. Next day, the reaction was diluted with ethyl acetate 80 mL, washed with brine (80 mL), dried over sodium sulfate, and concentrated to a crude product which was then purified by flash column chromatography, SiO2, gradient 20-100% ethyl acetate/hexane to give a white solid, 1.11 g of product, contaminated with the impurity of mass 182 (byproduct from the boronic ester, compound 6). MS (ES) [M+H] calc'd for C25H27FN6O3, 479. found, 479.4.

1. customthe mixture was purged with nitrogen for 5 minutes
2. addition1,1′-bis(diphenylphosphino)ferrocenedichloro palladium(II) dichloromethane complex (0.136 g, 0.186 mmol) was then added
3. washwashed with brine (80 mL)
4. dry with materialdried over sodium sulfate
5. concentrationconcentrated to a crude product which
6. customwas then purified by flash column chromatography, SiO2, gradient 20-100% ethyl acetate/hexane