反应详情

To a solution of N-[3-(3-amidinophenyl)-2-(E)-propenyl]-N-[3-carbamoyl-4-[1-(4,5-dihydro-3H-pyrrol-2-yl)piperidin-4-yloxy]phenyl]methanesulfonamide dihydrochloride (0.29 g) obtained in example 99(b) in a mixture of dichloromethane (3 ml) and acetonitrile (3 ml) were added successively 4-nitrophenyl acetate (0.09 g) and triethylamine (0.26 ml) with stirring under ice-cooling, and the resulting mixture was stirred at room temperature for 4 hours. After stirring, to the reaction mixture was added dichloromethane, and the organic layer was washed successively with a 0.5N aqueous sodium hydroxide solution and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and evaporated in vacuo. The residue obtained was purified by chromatography on a silica gel column using a mixed solvent of dichloromethane and methanol (50:0˜47:3). The solid obtained was dissolved in water and then lyophilized to afford the title compound (0.16 g, yield: 58%) as a pale yellow amorphous solid.

1. temperaturecooling
2. stirringthe resulting mixture was stirred at room temperature for 4 hours
3. stirringAfter stirring, to the reaction mixture
4. washthe organic layer was washed successively with a 0.5N aqueous sodium hydroxide solution
5. dry with materiala saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate
6. customevaporated in vacuo
7. customThe residue obtained
8. customwas purified by chromatography on a silica gel column
9. customThe solid obtained