N1-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamide → N-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzamide

Participants

Reaction Steps

Step 12 (B): Preparation of N1-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-5-(oxazol-2-yl)-N3,N3-dipropylisophthalamide. The solution of (2R,4R)-tert-butyl 2-((1S,2S)-2-(3-(benzamido)-5-(oxazol-2-yl)benzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate (step 12 (A), 110 mg) in HCl (4.0 M solution in dioxane, 2 mL) was added 4 drops of H2O and the mixture was stirred at rt for 2 h. The solvent was removed and the mixture was purified by reverse phase HPLC (30×100 mm PHENOMENEX-LUNA S10 column, 42-82% methanol/H2O/0.1% TFA) to give the title compound: 1H NMR (CD3OD, 500 MHz) δ ppm 0.74 (3H, m), 0.97 (3H, m), 1.03 (3H, m), 1.57 (1H, dd, J=5, 15 Hz), 1.63 (1H, m), 1.76 (2H, dd, J=5, 15 Hz), 2.19 (1H, m), 2.54 (1H, m), 2.90 (1H, dd, J=10, 15 Hz), 3.21 (2H, m), 3.35-3.53 (7H, m), 3.85 (1H, m), 4.08 (1H, dd, J=5, 10 Hz), 4.23-4.30 (2H, m), 6.75 (1H, m), 6.92 (2H, m), 7.37 (1H, s), 7.71 (1H, m), 8.06 (1H, s), 8.13 (1H, m), 8.39 (1H, m). MS (ESI) (M+H)+ 613.27.

Provenance & Evidence