反应详情

A mixture of 4-((R)-4-((R)-3-((diethylamino)methyl)morpholino)-4-oxo-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 91, 200 mg, 0.31 mmol) and 1 M borane-tetrahydrofuran complex (662 μl, 0.66 mmol) was stirred at room temperature for 16 hours. The reaction mixture was treated carefully with MeOH (5 ml) and concentrated HCl (1 ml). The mixture was heated at 80° C. for 3 hours, cooled to r.t, and the pH was adjusted to pH 10 with 4 N aqueous sodium carbonate. The mixture was diluted with ethyl acetate (300 ml), washed successively with water (150 ml) and brine (150 ml), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by column chromatography (ISCO, eluting with 0→20% MeOH/DCM over 15 minutes) to give the title product (109 mg, yield: 56%).

1. temperatureThe mixture was heated at 80° C. for 3 hours
2. temperaturecooled
3. washwashed successively with water (150 ml) and brine (150 ml)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe concentrate was purified by column chromatography (ISCO, eluting with 0→20% MeOH/DCM over 15 minutes)