反应详情

To a solution of 4′-[[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylcarboxylic acid (60.0 mg) in N,N-dimethylformamide (0.450 ml) was added 1,1′-carbonylbis-1H-imidazole (18.3 mg) and the mixture was stirred at room temperature for 1.5 hours under nitrogen atmosphere. To the mixture were added 2,3,4,6,7,8,9,10-octahydropyrimido-[1,2-a]azepine (0.0185 ml) and a solution of 3-(aminosulfonyl)propyl acetate (22.4 mg) in N,N-dimethylformamide (0.300 ml) and the mixture was stirred at room temperature for 2 days. The reaction mixture was warmed to 120° C. and stirred at the same temperature for 2 hours. After cooling to room temperature, the reaction mixture was extracted with ethyl acetate, washed with water and brine and dried over magnesium sulfate. Filtration followed by evaporation gave the crude product which was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/3 to 1/1) to give 3-[[[[4′-[[2-[(tert-butoxycarbonyl)[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]ethyl]amino]-3-isobutoxy-4-biphenylyl]carbonyl]amino]sulfonyl]propyl acetate (34.1 mg) as a yellow paste.

1. temperatureThe reaction mixture was warmed to 120° C.
2. stirringstirred at the same temperature for 2 hours
3. temperatureAfter cooling to room temperature
4. extractionthe reaction mixture was extracted with ethyl acetate
5. washwashed with water and brine
6. dry with materialdried over magnesium sulfate
7. filtrationFiltration
8. customfollowed by evaporation
9. customgave the crude product which
10. customwas purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=1/3 to 1/1)