反应详情

To 4 ml of toluene was added 245 mg of (N,N-dimethylformamide-dimethyl sulfate) complex compound, and 66 mg of sodium methoxide was added thereto with ice-cooling after which the resulting mixture was subjected to reaction at room temperature for 30 minutes. Subsequently, 200 mg of ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]acetate was added thereto, and the resulting mixture was subjected to reaction under reflux for 5 hours. To the reaction mixture were added 20 ml of chloroform and 20 ml of water, and the organic layer was separated, washed with 20 ml of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the residue thus obtained was purified by a column chromatography [Wako Silica Gel C-200, eluant: chloroform-ethanol (50:1 by volume)] to obtain 190 mg (yield 84.9%) of ethyl 2-[6-(3-acetylamino-1-pyrrolidinyl)-2-(2,4-difluorophenylamino)-5-fluoronicotinoyl]-3 -(N,N-dimethylamino)acrylate having a melting point of 184°-186° C.

1. additionwas added
2. temperaturewith ice-cooling after which the resulting mixture
3. customwas subjected to reaction at room temperature for 30 minutes
4. customthe resulting mixture was subjected to reaction
5. temperatureunder reflux for 5 hours
6. customthe organic layer was separated
7. washwashed with 20 ml of saturated aqueous sodium chloride solution
8. dry with materialdried over anhydrous magnesium sulfate
9. customThe solvent was removed by distillation under reduced pressure
10. customthe residue thus obtained
11. customwas purified by a column chromatography [Wako Silica Gel C-200, eluant: chloroform-ethanol (50:1 by volume)]