반응 단계
Step 15 (A): (2R,4R)-tert-Butyl 2-((1S,2S)-1-(tert-butyldimethylsilyloxy)-2-(3-(carbamoyl)benzamido)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate. To a solution of 3-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)benzoic acid (Step 1 (C), 40 mg, 0.06 mmol) in dichloromethane (1.5 mL) was added Hunig's base (24 mg, 0.18 mmol) to make a clear solution and HATU (28 mg, 0.072 mmol) was then added. After stirring for 20 min, the reaction mixture was added 1-phenylethanamine (15 mg, 0.12 mmol) and the reaction mixture was stirred at rt overnight. The reaction mixture was concentrated under vacuum and purified by silica gel Flash Chromatography (0% to 15% to 30% EtOAc/Hexane step gradient) to give 40 mg of the title compound (87% yield): 1H NMR (CDCl3, 500 MHz) δ 0.01 (3H, s), 0.05 (3H, s), 0.85 (9H, s), 0.89 (3H, m), 1.46 (9H, s), 1.50 (2H, m), 1.58 (3H, d, J=5 Hz), 2.02-2.05 (1H, m), 2.20 (1H, dd, J=5, 10 Hz), 2.64 (1H, m), 2.88-2.94 (1H, m), 3.30-3.37 (3H, m), 3.78 (1H, dd, J=5, 15 Hz), 4.00 (1H, m), 4.07-4.13 (2H, m), 4.60 (1H, m), 5.33 (1H, m), 6.56-6.61 (2H, m), 6.77 (2H, d, J=10 Hz), 7.25 (1H, m), 7.32 (2H, m), 7.37 (2H, m), 7.48 (1H, m), 7.97-8.01 (2H, m), 8.20 (1H, m), 8.24-8.31 (1H, m). MS (ESI) (M+H)+ 780.49.
