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 (0.23 g) obtained in example 99(b) in a mixture of dichloromethane (4.5 ml) and N,N-dimethylformamide (1.5 ml) were added successively ethyl 4-nitrophenyl carbonate (0.10 g) obtained in example 103 and triethylamine (0.16 ml) at room temperature, and the resulting mixture was stirred at room temperature overnight and then 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). Subsequently, to a solution of the oily product obtained in ethanol (2 ml) was added a 4N solution of hydrogen chloride in dioxane (0.5 ml), and the resulting mixture was evaporated to dryness in vacuo. The amorphous solid obtained was dissolved in dichloromethane, and the resulting mixture was extracted with 1N hydrochloric acid, and the aqueous layer collected was evaporated in vacuo. The residue obtained was dissolved in water and then lyophilized to afford the title compound (0.20 g, yield: 84%) as a colorless amorphous solid.

1. customevaporated in vacuo
2. customThe residue obtained
3. customwas purified by chromatography on a silica gel column
4. customSubsequently, to a solution of the oily product obtained in ethanol (2 ml)
5. customthe resulting mixture was evaporated to dryness in vacuo
6. customThe amorphous solid obtained
7. extractionthe resulting mixture was extracted with 1N hydrochloric acid
8. customthe aqueous layer collected
9. customwas evaporated in vacuo
10. customThe residue obtained