反应详情

A mixture of (S)-2-amino-1-benzoxazol-2-yl-2-methyl-pentan-1-one hydrochloride (80.6 mg, 0.3 mmol), (S)-4,4-difluoro-2-[(morpholine-4-carbonyl)-amino]-5-phenyl-pentanoic acid (0.102 mg, 0.3 mmol), EDCI (69 mg, 0.36 mmol), HOBT (48.6 mg, 0.36 mmol) and Diisopropyl ethylamine (0.2 mL) in DMF is stirred at room temperature overnight. The reaction mixture is diluted with ethyl acetate, washed with cold 1N HCl, saturated NaHCO3 and then saturated NaCl solution. The organic phase is dried over magnesium sulfate and solvent evaporated under reduced pressure to give the crude product. Purification by Silica gel column chromatography, eluting with ethyl acetate and heptane mixture gives morpholine-4-carboxylic acid {(S)-1-[(S)-1-(benzoxazole-2-carbonyl)-1-methyl-butylcarbamoyl]-3,3-difluoro-4-phenyl-butyl}-amide (82%).

1. washwashed with cold 1N HCl, saturated NaHCO3
2. dry with materialThe organic phase is dried over magnesium sulfate and solvent
3. customevaporated under reduced pressure
4. customto give the crude product
5. customPurification by Silica gel column chromatography
6. washeluting with ethyl acetate and heptane mixture