反应详情

To 4 ml of toluene was added 540 mg of (N,N-dimethylformamide-dimethyl sulfate) complex compound, and 85 mg of sodium methoxide was added thereto at 0° C., after which the resulting mixture was subjected to reaction at 0° to 10° C. for 1 hour. Subsequently, 200 mg of ethyl 2-[2-(2,4-difluorophenylamino)-5-fluoro-6-methoxynicotinoyl]acetate was further added to the reaction mixture, and the resulting mixture was subjected to reaction under reflux for 1.5 hours. The reaction mixture was added to a mixture of 8 ml of ethyl acetate and 8 ml of water, and the organic layer was separated, washed with 5 ml of saturated aqueous sodium chloride solution, and then dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and to the crystalline material thus obtained was added 1 ml of diethyl ether, after which crystals were collected by filtration to obtain 170 mg (yield 82.8%) of ethyl 1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-7-methoxy-4-oxo-1,8-naphthyridine-3-carboxylate. The physical properties of this compound were identical with those of the compound obtained in Example 41.

1. additionwas added
2. customat 0° C., after which the resulting mixture was subjected to reaction at 0° to 10° C. for 1 hour
3. customthe resulting mixture was subjected to reaction
4. temperatureunder reflux for 1.5 hours
5. customthe organic layer was separated
6. washwashed with 5 ml of saturated aqueous sodium chloride solution
7. dry with materialdried over anhydrous magnesium sulfate
8. customThe solvent was removed by distillation under reduced pressure
9. customto the crystalline material thus obtained
10. filtrationafter which crystals were collected by filtration