反应详情

4-(4-((R)-(4′-chlorobiphenyl-2-yl)((S)-1,1-dimethylethylsulfinamido)methyl)piperidin-1-yl)benzoic acid (INTERMEDIATE 130, 0.150 g, 0.29 mmol), DMAP (70 mg, 0.57 mmol), and EDC (0.110 g, 0.57 mmol) were placed in a 40 ml vial and flushed with nitrogen. DCM (4.0 ml) and DIPEA (0.10 ml, 0.57 mmol) were added, and the solution was stirred at r.t for 10 minutes. A solution of (R)-4-(4-morpholino-1-(phenylthio)butan-2-ylamino)-3-(trifluoromethylsulfonyl)benzenesulfonamide (INTERMEDIATE 69, 0.158 g, 0.29 mmol) in DCM (1.6 ml) was added to the solution and the reaction mixture was stirred at r.t overnight. The mixture was diluted with DCM and washed with 1N sodium bisulfate (aq.) followed by a saturated aq. sodium bicarbonate. The organic layer was dried (Na2SO4), filtered, and evaporated under reduced pressure to give a residue which was purified by column chromatography (ISCO, silica gel column, eluting with 0→100% DCM/MeOH/NH3 (10:1:0.1 v/v/v)) to provide the title compound (0.21 g, yield: 69%).

1. customflushed with nitrogen
2. stirringthe reaction mixture was stirred at r.t overnight
3. washwashed with 1N sodium bisulfate (aq.)
4. dry with materialThe organic layer was dried (Na2SO4)
5. filtrationfiltered
6. customevaporated under reduced pressure
7. customto give a residue which
8. customwas purified by column chromatography (ISCO, silica gel column, eluting with 0→100% DCM/MeOH/NH3 (10:1:0.1 v/v/v))