Pyrrolidine → 2-{1-[(4S,5R)-2-(6-tert-Butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-1-pyrrolidin-1-yl-ethanone

Participants

Reaction Steps

To a suspension of {1-[(4S,5R)-2-(6-tert-butyl-4-ethoxy-pyridin-3-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperidin-4-yl}-acetic acid (75.0 mg, 0.112 mmole) in dimethylformamide (6 mL) were added successively 1-hydroxybenzotriazole (23.0 mg, 0.169 mmole, Chem-Impex), N,N,N′,N′-tetramethyl-O-(1H-benzotriazol-1-yl)uranium hexafluorophosphate (64.0 mg, 0.169 mmole, Aldrich) and diisopropylethylamine (58 mg, 0.448 mmole). The mixture was stirred for 15 min before pyrrolidine (12.0 mg, 0.169 mmole, Aldrich) was added. The reaction mixture was allowed to stir for 2 h before concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with 1 N sodium hydroxide, brine, dried and concentrated. The crude residue was purified by flash column chromatography (silica gel, eluting with a gradient of 1-10% methanol in methylene chloride) to give the title compound (71.8 mg, 89% yield). HR-MS (ES, m/z) calculated for C40H50Cl2N5O3 [(M+H)+] 718.3285, observed 718.328.

Provenance & Evidence