Diisopropylethylamine → ((3E)-1,1-Dimethyl-4-{N-methyl-N-[(1R)1-(N-methyl-N-{(1R)-1-[N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamoyl}but-3-enyl)carbamic acid tert-butyl ester

(2E)-5-(tert-Butoxycarbonylamino)-5-methylhex-2-enoic acid (2.87 g, 11.8 mmol), 1-hydroxy-7-azabenzotriazole (1.6 g, 11.8 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.26 g, 11.8 mmol) were dissolved in dichloromethane (30 mL). The reaction mixture was stirred for 15 min. Ethyidiisopropylamine (2.0 mL, 11.8 mmol) was added. (2R)-N-Methyl-2-(methylamino)-N-{(1R)-1-[N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl]-2-phenylethyl}-3-(2-naphthyl)propionamide (6.0 g, 11.8 mmol) dissolved in dichloromethan (10 mL) was added. The reaction mixture was stirred for 16 h. The reaction mixture was washed with sat. aqueous sodium hydrogen carbonate solution (100 mL). The aqueous phase was extracted with dichloromethane (100 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 (400 g), using ethyl acetate as eluent, to give 5.28 g of ((3E)-1,1-Dimethyl-4-{N-methyl-N-[(1R)1-(N-methyl-N{(1R)-1-[N-methyl-N-(2-(pyridin-2-yl)ethyl)carbamoyl]-2-phenylethyl}carbamoyl)-2-(2-naphthyl)ethyl]carbamoyl}but-3-enyl)carbamic acid tert-butyl ester.

1. additionwas added
2. stirringThe reaction mixture was stirred for 16 h
3. washThe reaction mixture was washed with sat. aqueous sodium hydrogen carbonate solution (100 mL)
4. extractionThe aqueous phase was extracted with dichloromethane (100 mL)
5. dry with materialThe combined organic layers were dried over magnesium sulfate
6. customThe solvent was removed in vacuo
7. customThe crude product was purified by flash chromatography on silica (400 g)

ORDレコード

ord-4c00cd920b314a81a4792296d5b1d5e5

出典データセット

uspto-grants-2003_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US06566337B1