反应详情

Hydrogen chloride gas was bubbled into a suspension of 4′-{[5-(3-cyano-benzyloxy)-4-hydroxymethyl-6-methyl-pyridin-3-ylmethyl]-amino}-biphenyl-2-sulfonic acid tert-butylamide (13) (100 mg, 0.17 mmol) in absolute ethyl alcohol (30 mL) at 0° C. for 30 minutes. The septum was replaced and the reaction mixture was stirred at room temperature overnight. Hydrogen chloride gas was purged with nitrogen gas for 2 hours and the solvent evaporated to give the crude amide ester as a solid. Ammonia in methyl alcohol (30 mL, 7 M, 350 mmol) was added to the crude amide ester and the reaction mixture was stirred overnight at room temperature. The solvent was evaporated and the product purified on a silica gel column using a mixture of dichloromethane:methyl alcohol (4:1) as eluant to give the corresponding 3-{4-hydroxymethyl-5-[(2′-sulfamoyl-biphenyl-4-ylamino)-methyl]-pyridin-3-yloxymethyl}-benzamidine (14) (90 mg, 97% yield) as a colorless powder.

1. customHydrogen chloride gas was purged with nitrogen gas for 2 hours
2. customthe solvent evaporated
3. customto give the crude amide ester as a solid
4. stirringthe reaction mixture was stirred overnight at room temperature
5. customThe solvent was evaporated
6. customthe product purified on a silica gel column
7. additiona mixture of dichloromethane:methyl alcohol (4:1) as eluant