反应详情

温度

0 °C

A dry flask containing 5-bromo-2-(4-methoxyphenyl)pyridin-3-amine (0.14 g, 0.52 mmol) in dry DMF (5.0 mL) was cooled to 0° C., then sodium hydride, 60% dispersion in mineral oil (0.043 g, 1.07 mmol) was added carefully in portions. The mixture was stirred at 0° C. for 15 min, then 4-chloro-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.18 g, 0.62 mmol) was added in portions. Upon complete addition, the mixture was warmed to 60° C. After 18 h, the reaction was cooled to rt then was carefully treated with 10% sodium carbonate solution. The black mixture was subsequently extracted five times with DCM:MeOH (90:10). The organic extraction was then washed one time with brine and dried over anhydrous magnesium sulfate. After filtration and concentration, the black residue was purified on silica gel (50-100% EtOAc in hexanes) to afford a mostly N-(5-bromo-2-(4-methoxyphenyl)pyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. Mass Spectrum (ESI) m/e=533.0 (M+1).

1. additionUpon complete addition
2. temperaturethe mixture was warmed to 60° C
3. waitAfter 18 h
4. temperaturethe reaction was cooled to rt
5. extractionThe black mixture was subsequently extracted five times with DCM:MeOH (90:10)
6. extractionThe organic extraction
7. washwas then washed one time with brine
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationAfter filtration and concentration
10. customthe black residue was purified on silica gel (50-100% EtOAc in hexanes)