反应详情

A mixture of chiral-(2R,3S,4R,5S)-3-(3-chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (150 mg, 0.321 mmol), ethyl 5-amino-1H-indole-2-carboxylate (114 mg, 0.558 mmol), 2-(7-azabenzotriazol-1-yl)-n,n,n′,n′-tetramethyluronium hexafluorophosphate (HATU, 159 mg, 0.417 mmol) and iPr2NEt (0.4 mL, 2.29 mmol) in CH2Cl2 (10 mL) was stirred at rt overnight. The mixture was then diluted with CH2Cl2 and washed with water, brine. The organic phase was separated, then concentrated and purified by RP-HPLC chromatography (20-95% acetonitrile/water) to afford 5-{[(2R,3S,4R,5S)-3-(3-Chloro-2-fluoro-phenyl)-4-(4-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)pyrrolidine-2-carbonyl]-amino}-1H-indole-2-carboxylic acid ethyl ester (37 mg, 17.6%) as an off-white powder. LCMS (ES+) m/z Calcd for C34H32Cl2F2N4O3+H [(M+H)+]: 652.18. found: 6512.

1. washwashed with water, brine
2. customThe organic phase was separated
3. concentrationconcentrated
4. custompurified by RP-HPLC chromatography (20-95% acetonitrile/water)