Diisopropylethylamine → ((3E)-4-(N-((1R)-1-(N-(2-(2-(methylsulfonylamino)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamoyl)-1,1-dimethylbut-3-enyl)carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of (2E)-5-(tert-butoxycarbonylamino)-5-methylhex-2-enoic acid (86 mg, 0.35 mmol) and 1-hydroxy-7-azabenzotriazole (48 mg, 0.35 mmol) in N,N-dimethylformamide (1.5 ml) and dichloromethane (1.8 ml) was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (68 mg, 0.35 mmol) was added. The reaction mixture was stirred for 15 min at 0° C. A solution of (2R)-N-(2-(2-(methylsulfonylamino)phenyl)ethyl)-N-methyl-2-(methylamino)-3-(2-naphthyl)propionamide (155 mg, 0.35 mmol) in dichloromethane (2 ml) and ethyldiisopropylamine (0.06 ml, 0.35 mmol) were added successively. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (50 ml) and washed with 10% aqueous sodium hydrogen sulfate solution (50 ml). The aqueous phase was extracted with ethyl acetate (3×20 ml). The combined organic layers were washed with saturated aqueous sodium hydrogen carbonate solution (50 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (40 g), using ethyl acetate/heptane (2:1), as eluent, to give 174 mg of ((3E)-4-(N-((1R)-1-(N-(2-(2-(methylsulfonylamino)phenyl)ethyl)-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamoyl)-1,1-dimethylbut-3-enyl)carbamic acid tert-butyl ester.

Provenance & Evidence