Diisopropylethylamine → N-methyl-N-((3E)-1,1-dimethyl-4-(N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)but-3-enyl)carbamic acid tert-butyl ester

温度

0 °C

##STR115## (2E)-5-(N-(tert-Butoxycarbonyl)-N-methylamino)-5-methylhex-2-enoic acid (146 mg, 0.57 mmol) was dissolved in dichloromethane (2 ml) and N,N-dimethylformamide (2 ml). 1-Hydroxy-7-azabenzotriazole (72 mg, 0.57 mmol) was added as a solid. The solution was cooled to 0° C. N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (109 mg, 0.57 mmol) was added. The solution was stirred for 15 min at 0° C. A solution of (2R)-N-Methyl-2-(methylamino)-3-(2-naphthyl)-N-(2-(2-thienyl)ethyl)propionamide (200 mg, 0.57 mmol) in dichloromethane (2 ml) was added. Ethyldiisopropylamine (0.1 ml, 0.57 mmol) was added. 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 1N hydrochoric acid. The aqueous phase was extracted with ethyl acetate (2×20 ml). The combined organic layers were washed with saturated sodium hydrogen carbonate solution (40 ml) and dried over magnesium sulfate. The solvent was removed in vacuo. The crude product was purified by flash chromatography on silica (80 g), using ethyl acetate/heptane as eluent, to give 270 mg of N-methyl-N-((3E)-1,1-dimethyl-4-(N-methyl-N-((1R)-1-(N-methyl-N-(2-(2-thienyl)ethyl)carbamoyl)-2-(2-naphthyl)ethyl)carbamoyl)but-3-enyl)carbamic 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 1N hydrochoric acid
4. extractionThe aqueous phase was extracted with ethyl acetate (2×20 ml)
5. washThe combined organic layers were washed with saturated sodium hydrogen carbonate solution (40 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 (80 g)

ORDレコード

ord-4fb79b9b51b248a1a9bfdef3fa9b10e0

出典データセット

uspto-grants-1999_07

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05922770