1,1'-Carbonyldiimidazole → HCID 57741526, compound

Participants

Reaction Steps

Dissolve racemic 3′,5′-dichloro-4′-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carboxylic acid (0.200 g, 0.448 mmol) in dichloromethane (5 mL) and add 1,1′-carbonyl-diimidazole (0.125 g, 0.760 mmol). Stir under argon atmosphere at room temperature and check reaction progress via TLC. Add 4-amino-piperidine-1-carboxylic acid tert-butyl ester (0.180 g, 0.90 mmol) and continue to stir until the starting material has been fully consumed. Dilute the reaction with dichloromethane (50 mL) and wash with 1.0 N sodium hydroxide (30 mL) then brine (30 mL). Collect the organic phase, dry over anhydrous magnesium sulfate and concentrate under reduced pressure. Purify via flash chromatography by eluding with gradient (0-100%) dichloromethane to 15% ammonia methanol/85% dichloromethane. After concentrating, dissolve the 4-{[3′,5′-dichloro-4′-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-biphenyl-4-carbonyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester in dioxane (20 mL), add 4N hydrochloric acid -dioxane (10 mL) and stir ½ hour to obtain an oily residue in reaction vessel. Concentrate the mixture under vacuum then dilute in dichloromethane (100 mL). Quench with saturated aqueous sodium bicarbonate solution (50 mL), dry the organic phase over magnesium sulfate and concentrate to obtain 0.195 g (82%) of a yellow foam: MS (m/z): 530 (M+2).

Provenance & Evidence