反应详情

To a suspension of 31 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 1 ml of N,N-dimethylformamide were added successively dropwise 0.044 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.011 ml of isoamyl nitrite, and the mixture was stirred. After disappearance of hydrazide compound, the reaction mixture was cooled to +30° C., and neutrlized by adding 0.031 ml of triethylamine to prepare a solution of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)-propionyl]-L-histidine azide. The azide solution prepared was added dropwise to a solution of 16 mg of (2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl benzyl ether hydrochloride and 0.011 ml of triethylamine in 1 ml of N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours under ice-cooling. A 5% aqueous sodium bicarbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated sodium chloride aqueous solution, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by preparative silica gel thin layer chromatograpy (developing solvent: lower layer of chloroform/methanol/water=8/3/1 by volume) to obtain 18 mg of (2RS, 3S)-3-{N-(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexyl benzyl ether as a white powder.

1. temperaturecooling
2. temperaturecooling
3. extractionthe mixture was extracted with ethyl acetate
4. washThe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
5. dry with materialdried over anhydrous magnesium sulfate
6. customevaporated under reduced pressure
7. customThe residue was purified by preparative silica gel thin layer chromatograpy (developing solvent: lower layer of chloroform/methanol/water=8/3/1 by volume)