反应详情

Step 7 (B): Preparation of N1-butyl-N3-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1(2R)-4-phenylpyrrolidin-2-yl)propan-2-yl)-N1-methylisophthalamide. To a solution of (R)-tert-butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-2-(3-(carbamoyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-phenyl-2,3-dihydropyrrole-1-carboxylate (Step 7 (A), 15 mg) in MeOH (1 mL) was added a catalytic amount of Pd on activated charcoal (10 wt %, 10 mg). The reaction mixture was put on hydrogenator at 50 psi for 3 h. The mixture was then filtered and concentrated in vacuo. To the above residue were added dioxane (0.5 mL) and 2 drops of H2O and the mixture was stirred at rt for 2 h. Solvent was removed and the mixture was purified by reverse phase HPLC to give the title compound (9 mg): 1H NMR (CDCl3, 500 MHz) δ 0.77 (2H, m), 1.03 (2H, m), 1.14 (1H, dd, J=10, 15 Hz), 1.45 (1H, dd, J=5, 15 Hz), 1.54 (1H, m), 1.69 (1H, m), 2.33 (1H, m), 2.58 (1H, m), 2.89 (1H, m), 2.94 (1H, s), 3.09 (1H, s), 3.23-3.29 (2H, m), 3.44 (1H, dd, J=5, 15 Hz), 3.57 (2H, m), 3.74 (1H, m), 4.00 (1H, m), 4.17 (1H, m), 4.26 (1H, m), 6.74 (1H, t, J=10 Hz), 6.89 (2H, d, J=10 Hz), 7.31 (1H, m), 7.36-7.40 (4H, m), 7.53-7.56 (2H, m), 7.67 (1H, s), 7.76-7.78 (1H, m). MS (ESI) (M+H)+ 550.31.

1. filtrationThe mixture was then filtered
2. concentrationconcentrated in vacuo
3. additionTo the above residue were added dioxane (0.5 mL) and 2 drops of H2O
4. customSolvent was removed
5. customthe mixture was purified by reverse phase HPLC