反应详情

To a solution of 3.0 g (0.0074 mol) of 4-(3-chlorophenyl)-2-(4,6-dimethoxypyrimidin-2-ylthio)nicotinic acid in 30 ml of N,N-dimethylformamide was added 1.50 g (0.0093 mol) of carbonyldiimidazole with stirring, and the mixture was stirred at room temperature for 24 hours. To a suspension of 0.60 g (0.0015 mol) of 60% sodium hydride in 30 ml of N,N-dimethylformamide was added 1.8 g (0.0019 mol) of methanesulfonamide and stirred at 80° C. for 2 hours. Thereafter, the above prepared N,N-dimethylformamide solution of carbonylimidazole of nicotinic acid was added thereto at room temperature, and the mixture was stirred at 80° C. for 2 hours. The reaction mixture was then poured into water, and washed with 50 ml of ethyl acetate. Thereafter, the aqueous layer was acidified with 10% HCl, and extracted with 100 ml of ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, filtrated and concentrated. The concentrate was purified by silica gel column chromatography (eluting solvent: ethyl acetate/hexane=1/1) to obtain 3.0 g of a light-yellowish glass-like aimed product.

1. stirringthe mixture was stirred at room temperature for 24 hours
2. stirringstirred at 80° C. for 2 hours
3. additionwas added
4. stirringat room temperature, and the mixture was stirred at 80° C. for 2 hours
5. washwashed with 50 ml of ethyl acetate
6. extractionextracted with 100 ml of ethyl acetate
7. washThe organic layer was washed with water
8. dry with materiala saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate
9. filtrationfiltrated
10. concentrationconcentrated
11. customThe concentrate was purified by silica gel column chromatography (eluting solvent: ethyl acetate/hexane=1/1)