Triethylamine → N-[(3S,6R)-1-(cyclopropylmethyl)-2-oxo-6-phenylazepan-3-yl]-4-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidine-1-carboxamide

Participants

Reaction Steps

Triethylamine (0.070 mL, 0.51 mmol) was added to a solution of 3-amino-1-(cyclopropylmethyl)-6-phenylazepan-2-one (131 mg, 0.51 mmol) and p-nitrophenyl chloroformate (102 mg, 0.51 mmol) in tetrahydrofuran (5 mL) at 0° C. After 0.5 h, triethylamine (0.18 mL, 1.28 mmol) and 4-(2-oxo-4-phenyl-2,3-dihydro-1H-imidazol-1-yl)piperidinium chloride (142 mg, 0.51 mmol) were added and the mixture was allowed to warm to ambient temperature. After 2 h, the mixture was concentrated. Purification by preparative reverse phase chromatography (DeltaPak C18, 15 □, 47 mm×300 mm, 65 mL/min: 5% CH3CN to 95% CH3CN over 60 min) afforded the racemic compound. The cis and trans enantiomers were both separated using a Chiralcel AD column eluting with 30% 2-propanol/hexanes→70% propanol/hexanes (0.1% diethylamine in hexanes) to give the title compound (50 mg). MS 528.3 (M+1)

Provenance & Evidence