Diisopropylethylamine → HCID 11061050, compound

Participants

Reaction Conditions

Reaction Steps

At 0° C., N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (530 mg, 2.76 mmol) was added to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)-propionic acid (911 mg, 2.76 mmol) and 1-hydroxy-7-azabenzotriazole (376 mg, 2.76 mmol) in dichloromethane (5 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of (2R)-1-((2S)-2-((dimethylamino)methyl)pyrrolidin-1-yl)-2-methylamino-3-phenylpropan-1-one (800 mg, 2.76 mmol) in dichloromethane (5 ml) and N,N-dimethylformamide (5 ml) and ethyldiisopropylamine (0.71 ml, 4.15 mmol) were added successively. The reaction mixture was stirred for 3 days, while it was warming up to room temperature. It was diluted with ethyl acetate (100 ml) and washed with a saturated aqueous solution of sodium hydrogen carbonate (100 ml). The aqueous solution was extracted with ethyl acetate (3×70 ml). The combined organic layers were dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (90 g), using dichloromethane/methanol/25% aqueous ammonia (200:10:1) as eluent, to give 1.37 g of N-((1R)-1-{N-[(1R)-1-benzyl-2-((2S)-2-((dimethylamino)methyl)pyrrolidin-1-yl)-2-oxoethyl]-N-methylcarbamoyl}-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl ester.

Provenance & Evidence