反应详情

0.5 g N4-(3-Chloro-4-fluoro-phenyl)-7-(2,2-difluoro-ethoxy)-quinazoline-4,6-diamine was dissolved in 10 ml THF and 1.2 ml N,N-Diisopropyl-ethylamine (DIEA) and 0.48 g 4-Bromo-but-2-enoyl chloride were added and the mixture was stirred at room temperature for 2 hours. 0.27 ml piperidine was added and stirred at room temperature overnight. An additional 0.7 ml piperidine was added and the mixture heated to 70° C. After 3 hours the reaction mixture was poured into water, the solids were extracted with ethyl acetate, washed with water and brine, dried over NaSO4 and flash chromatographed under 0-4% methanol in chloroform to yield 0.2 g 4-Piperidine-1-yl-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-(2,2-difluoro-ethoxy)-quinazolin-6-yl]-amide.

1. stirringstirred at room temperature overnight
2. temperaturethe mixture heated to 70° C
3. extractionthe solids were extracted with ethyl acetate
4. washwashed with water and brine
5. dry with materialdried over NaSO4 and flash
6. customchromatographed under 0-4% methanol in chloroform