反应详情

To a solution of (R)-4-(phenylthio)-3-(4-sulfamoyl-2-(trifluoromethylsulfonyl)phenylamino)butanoic acid (INTERMEDIATE 8, 500 mg, 1.00 mmol), (R)—N-ethyl-N-(morpholin-3-ylmethyl)ethanamine hydrochloride salt (INTERMEDIATE 90, 209 mg, 1.00 mmol), DIPEA (0.701 ml, 4.01 mmol) in DMA (5 ml) was added HATU (458 mg, 1.20 mmol). The mixture was stirred for 1 h at room temperature and diluted with ethyl acetate (200 ml). The mixture was washed successively with 1M aq. sodium bisulfate, saturated sodium bicarbonate, and brine. The organic phase was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified column chromatography (ISCO, eluting with 0→100% DCM/10% 2 M ammonia in MeOH in DCM over 24 minutes) to give the title product (200 mg, yield: 30.5%).

1. washThe mixture was washed successively with 1M aq. sodium bisulfate, saturated sodium bicarbonate, and brine
2. dry with materialThe organic phase was dried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated under reduced pressure
5. customThe concentrate was purified
6. washcolumn chromatography (ISCO, eluting with 0→100% DCM/10% 2 M ammonia in MeOH in DCM over 24 minutes)