反应详情

温度

70 °C

300 g of 4-Chloro-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinazolin-6-yl]-amide and 78 mg azepane were dissolved in 5 ml THF and purged with nitrogen. 0.25 ml DIEA was added and the mixture was stirred at 70° C. for 2 days. The mixture was then diluted with 20 ml ethyl acetate, washed with water and brine and dried over Na2SO4. The resulting solids were flash chromatographed with 0-4% methanol in chloroform. The product was dissolved in CH2Cl2 and treated with excess HCl and ether, then evaporated to dryness to give 115 mg of 4-Azepan-1-yl-but-2-enoic acid [4-(3-chloro-4-fluoro-phenylamino)-7-methoxy-quinazolin-6-yl]-amide (33% yield).

1. custompurged with nitrogen
2. addition0.25 ml DIEA was added
3. additionThe mixture was then diluted with 20 ml ethyl acetate
4. washwashed with water and brine
5. dry with materialdried over Na2SO4
6. customchromatographed with 0-4% methanol in chloroform
7. dissolutionThe product was dissolved in CH2Cl2
8. additiontreated with excess HCl and ether
9. customevaporated to dryness