Diisopropylethylamine → N-Methyl-N-[(1R)1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(pyridinyl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tert-butyl ester

Participants

Reaction Steps

(2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl) propionic acid (11.2 g, 34 mmol), 1-hydroxy-7-azabenzotriazole (5.2 g, 38 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (6.9 g, 36 mmol) were dissolved in dichloromethane (100 mL). The reaction mixture was stirred for 15 min. Ethyldiisopropylamine (7.0 mL, 41 mmol) was added. (2R)-N-Methyl-2-(methylamino)-3-phenyl-N-(2-(2-pyridyl)ethyl)propionamide (7.9 g, 27 mmol) dissolved in dichloromethane (20 mL) was added. The reaction mixture was stirred for 16 h. The reaction mixture was added to aminomethylresin (17.3 g, 13.5 mmol). The reaction mixture was stirred for 6 h. The reaction mixture was filtrated. The organic layer was washed with sat. aqueous sodium hydrogen carbonate solution (2×150 mL). The organic layer was dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (400 g), using ethyl acetate as eluent, to give 14.9 g N-Methyl-N-[(1R)1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(pyridinyl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamic acid tertbutyl ester.

Provenance & Evidence