反应详情

A solution of 3.00 g of ethyl 3-chlorocarbonyl-acrylate in 50 ml of tetrahydrofuran is added dropwise to 5.00 g of 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-7-cyclopropylmethoxy-quinazoline and 3.5 ml of diisopropylethylamine in 150 ml of tetrahydrofuran while cooling with an ice bath. The reaction mixture is stirred for a further hour while cooling with an ice bath and then stirred overnight at ambient temperature. Next, the solvent is largely distilled off in the rotary evaporator and the residue is partitioned between water and ethyl acetate. The organic phase is washed with saturated sodium chloride solution, dried over magnesium sulphate and concentrated by evaporation. The brown, oily crude product is stirred with diethylether, the precipitate formed is suction filtered and washed with a little diethylether. Yield: 3.20 g (47% of theory), Rf value: 0.80 (silica gel, ethyl acetate) Mass spectrum (ESI*): m/z=485, 487 [M+]*

1. temperaturewhile cooling with an ice bath
2. temperaturewhile cooling with an ice bath
3. stirringstirred overnight at ambient temperature
4. distillationNext, the solvent is largely distilled off in the rotary evaporator
5. customthe residue is partitioned between water and ethyl acetate
6. washThe organic phase is washed with saturated sodium chloride solution
7. dry with materialdried over magnesium sulphate
8. concentrationconcentrated by evaporation
9. stirringThe brown, oily crude product is stirred with diethylether
10. customthe precipitate formed
11. filtrationfiltered
12. washwashed with a little diethylether