反应详情

To a solution 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 (52.7 mg, 0.113 mmol) in dichloromethane (3 mL) were added DIPEA (71.2 mg, 0.55 mmol), 4-aminobenzhydrazide (33.1 mg, 0.22 mmol, Aldrich) and HATU (72.3 mg, 0.19 mmol). (The acid, DIPEA, and HATU were added in thirds at 20 min intervals). After 90 minutes the reaction was diluted with dichloromethane, washed with water and saturated sodium chloride and purified by HPLC with acetonitrile and water (with TFA 0.1% VAT) to give chiral (2R,3S,4R,5S)-4-(4-Chloro-2-fluoro-phenyl)-3-(3-chloro-2-fluoro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (4-hydrazinocarbonyl-phenyl)-amide (45.7 mg., 67.5%) as a white solid. HRMS (ES+) m/z Calcd C30H29Cl2F2N5O2+H [(M+H): 600.1739. Found: 600.1737.

1. washwashed with water and saturated sodium chloride
2. custompurified by HPLC with acetonitrile and water (with TFA 0.1% VAT)