反应详情

Step 15 (B): (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin 1-yl)-N-((1S,2S)-1-((2R,4S)-1-benzhydryl-4-hydroxypyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-4-phenylbutanamide. To a solution of (S)-2-((S)-3-acetamido-3-((R)-sec-butyl)-2-oxopyrrolidin-1-yl)-4-phenylbutanoic acid (Preparation A, 38.9 mg, 0.108 mmol) in DMF (2 mL) was added HATU (49.43 mg, 0.130 mmol). A solution of (3S,5R)-5-((1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl)-1-benzhydrylpyrrolidin-3-ol (Step 15 (A), 47.3 mg, 0.108 mmol) in DMF (2 mL) was then added, followed by N-methylmorpholine (42 μl, 0.378 mmol). The reaction mixture was stirred at rt for 3 h. pH 4 buffer was then added to quench. The mixture was extracted with ethyl acetate. The organic phase was washed with sat. aqueous NaCl, dried (MgSO4), and concentrated in vacuo. The crude mixture was purified by reverse phase Prep HPLC to give the title compound (60.5 mg, 72% yield) as a clear oil:

1. additionbuffer was then added
2. customto quench
3. extractionThe mixture was extracted with ethyl acetate
4. washThe organic phase was washed with sat. aqueous NaCl
5. dry with materialdried (MgSO4)
6. concentrationconcentrated in vacuo
7. customThe crude mixture was purified by reverse phase Prep HPLC