Ammonia → ethyl 4-cyclohexyl-1-[(R)-2-{3-[3-(3H-imidazol-4-yl)propyl]ureido}-3-(4-methoxyphenyl)propionyl]-piperidine-4-carboxylate

Participants

Reaction Steps

To 100 mg (0.24 mmol) of ethyl 1-[(R)-2-amino-3-(4-methoxyphenyl)propionyl]-4-cyclohexylpiperidine-4-carboxylate dissolved in 2 ml of DCM immersed in a bath of cold water are added 53 mg (0.26 mmol) of 4-nitrophenyl chloroformate. After warming to room temperature, the reaction medium is stirred for 2 hours and 30 minutes. The reaction is stopped by adding aqueous ammonia solution. The organic phase is then washed with water and then dried over MgSO4, filtered and concentrated. The oil obtained is dissolved in 4 ml of DMF at 80° C., and 110 mg (0.31 mmol) of 3-(1H-imidazol-4-yl)propylamine bis(trifluoroacetate), 0.05 ml of triethylamine are then added. The reaction mixture is left stirring at 80° C. for 15 minutes. After returning to room temperature, dichloromethane is added and the organic phase is washed with 1N sodium hydroxide solution. The organic phase is dried over MgSO4, filtered and concentrated. The crude product obtained is chromatographed on silica gel (eluent: 9/1 DCM/MeOH). 26 mg of ethyl 4-cyclohexyl-1-[(R)-2-{3-[3-(3H-imidazol-4-yl)propyl]ureido}-3-(4-methoxyphenyl)propionyl]-piperidine-4-carboxylate in the form of a colourless oil are obtained in a yield of 11%.

Provenance & Evidence