Triethylamine → (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-carbamoylmethyl-2-methoxy-phenyl)-amide

Participants

Reaction Conditions

Reaction Steps

To a solution of chiral (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}-3-methoxy-phenyl)-acetic acid (0.1 g, 0.17 mmol) prepared in Example 160 in anhydrous DMF (2 mL) were added EDCI (64 mg, 0.33 mmol), HOBt (45 mg, 0.33 mmol), NH4Cl (89 mg, 1.67 mmol), and triethylamine (34 mg, 0.33 mmol) sequentially. The reaction mixture was heated at 80° C. for 3 h. The mixture was cooled to room temperature, then partitioned between ethyl acetate and water. The organic layer was separated, and aqueous layer was extracted with ethyl acetate twice. The combined organic extract was washed with water, brine, dried over MgSO4, and concentrated. The residue was purified by chromatography (50-100% EtOAc in hexanes) to give chiral (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-carbamoylmethyl-2-methoxy-phenyl)-amide as a off white solid (81 mg, 77%).

Provenance & Evidence