反应详情

To a suspension of 207 mg of N-[2-(1-naphthylmethyl)-3-(ethylcarbamoyl)propionyl]-L-histidine hydrazide in 3 ml of dry N,N-dimethylformamide were added successively 0.30 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.076 ml of isoamyl nitrite at -20° C. with stirring. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C. and neutralized with 0.22 ml of triethylamine to prepare a solution of N-[2-(1-naphthylmethyl)-3-(ethylcarbamoyl)propionyl]-L-histidine azide. The cold azide solution was added dropwise to a solution of 100 mg of methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride and 0.66 ml of triethylamine in 2 ml of dry N,N-dimethylformamide under ice-cooling, and the mixture was stirred for 16 hours. 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 silica gel flash column chromatography (eluent chloroform/methanol=15/1, Rf1 =0.43) to obtain 77 mg of methyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(ethylcarbamoyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexanoate as a white powder.

1. temperaturecooling
2. customThe reaction mixture was evaporated under reduced pressure
3. additiona 5% aqueous sodium bicarbonate solution was added to the residue
4. extractionThe mixture was extracted with ethyl acetate
5. washthe ethyl acetate layer was washed with a saturated sodium chloride aqueous solution
6. dry with materialdried over anhydrous magnesium sulfate
7. customevaporated under reduced pressure
8. customThe residue was purified by silica gel flash column chromatography (eluent chloroform/methanol=15/1, Rf1 =0.43)