反应详情

To a suspension of 130 mg of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine hydrazide in 6 ml of dry N,N-dimethylformamide were added successively dropwise 0.19 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.05 ml of isoamyl nitrite, and the mixture was stirred. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C., and neutralized by adding 0.14 ml of triethylamine to prepare a solution of N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidine azide. The azide solution prepared was added drowise to a solution of 52 mg of (2RS, 3S)-3-amino-2-hydroxy-5-methylhexyl methyl ether hydrochloride and 0.05 ml of triethylamine in 2 ml of dry N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours under ice-cooling. The reaction mixture was evaporated under reduced pressure, and a 5% aqueous sodium bicarbonate solution was added to the residue. The mixture was extracted with ethyl acetate, and 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 chromatography (developing solvent: lower layer of chloroform/methanol/water32 8/3/1 by volume) to obtain 55 mg of (2RS, 3S)-3-{N-[(+)-2-(1-naphthylmethyl)-3-(phenethylcarbamoyl)propionyl]-L-histidyl}-amino-2-hydroxy-5-methylhexyl methyl ether as a white powder.

1. temperaturecooling
2. temperaturecooling
3. customThe reaction mixture was evaporated under reduced pressure
4. additiona 5% aqueous sodium bicarbonate solution was added to the residue
5. extractionThe mixture was extracted with ethyl acetate
6. washthe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
7. dry with materialdried over anhydrous magnesium sulfate
8. customevaporated under reduced pressure
9. customThe residue was purified by preparative silica gel thin layer chromatography (developing solvent: lower layer of chloroform/methanol/water32 8/3/1 by volume)