反应详情

温度

80 °C

To a solution of rac-4-{[(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carbonyl]-amino}-2-methoxy-benzoic acid prepared in Example 16 (55 mg, 0.09 mmol) in N,N-dimethylformamide (2 mL) was added EDCI (34 mg, 0.18 mmol), HOBt (24 mg, 0.18 mmol), NH4Cl (48 mg, 0.9 mmol), and triethylamine (18 mg, 0.18 mmol) sequentially. The reaction mixture was heated at 80° C. for 1 h. The mixture was poured into water, then extracted with ethyl acetate three times. The organic layers were combined, washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (25% to 100% EtOAc in hexanes) to give rac-(2′S,3′R,4′S,5′R)-6-chloro-4′-(3-chloro-2-fluoro-phenyl)-2′-(2,2-dimethyl-propyl)-2-oxo-1,2-dihydro-spiro[indole-3,3′-pyrrolidine]-5′-carboxylic acid (4-carbamoyl-3-methoxy-phenyl)-amide as a off white solid (Yield, 35 mg, 64%)

1. extractionextracted with ethyl acetate three times
2. washwashed with water, brine
3. dry with materialdried over MgSO4
4. concentrationconcentrated
5. customThe residue was purified by chromatography (25% to 100% EtOAc in hexanes)