反应详情

温度

0 °C

N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (594 mg, 3.1 mmol) was added at 0° C. to a solution of (2R)-2-(N-(tert-butoxycarbonyl)-N-methylamino)-3-(2-naphthyl)propionic acid (1.02 g, 3.1 mmol) and 1-hydroxy-7-azabenzotriazole (422 mg, 3.1 mmol) in dichloromethane (10 ml) and N,N-dimethylformamide (5 ml). The reaction mixture was stirred for 20 min at 0° C. A solution of the hydrochloride salt of crude (2S)-6-acetylamino-2-(((2R)-2-(methylamino)-3-phenylpropionyl)amino)hexanoic acid dimethylamide (1.28 g, 3.1 mmol) in dichloromethane (20 ml)and N,N-dimethylformamide (10 ml) and ethyidiisopropylamine (1.59 ml, 9.3 mmol) were added subsequently. The reaction mixture was stirred for 16 h, while it was warming up to room temperature. It was diluted with ethyl acetate (200 ml) and washed with a 10% aqueous sodium hydrogen sulfate solution (150 ml). The aqueous solution was extracted wtih ethyl acetate (3×100 ml). The combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (200 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (120 g), usin dichloromethane/methanol (10:1) as eluent, to give 1.57 g of N-((1R)-1-{N-[(1R)-1-((1S)-5-(acetylamino)-1-(dimethylcarbamoyl)pentylcarbamoyl)-2-phenylethyl]-N-methylcarbamoyl)-2-(2-naphthyl)ethyl)-N-methylcarbamic acid tert-butyl ester.

1. stirringThe reaction mixture was stirred for 16 h, while it
2. temperaturewas warming up to room temperature
3. washwashed with a 10% aqueous sodium hydrogen sulfate solution (150 ml)
4. extractionThe aqueous solution was extracted wtih ethyl acetate (3×100 ml)
5. washThe combined organic layers were washed with a saturated aqueous solution of sodium hydrogen carbonate (200 ml)
6. dry with materialdried over magnesium sulfate
7. customThe solvent was removed in vacuo
8. customThe crude product was purified by flash chromatography on silica (120 g)