Hydrochloric Acid → HCID 178501837, compound

Participants

Reaction Steps

To a solution of 100 mg of N-[2-(1-naphthylmethyl)-3-(dimethylcarbamoyl)propionyl]-L-histidine hydrazide in 5 ml of dry N,N-dimethylformamide were added successively 0.15 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.04 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 0.11 ml of triethylamine to prepare a solution of N-[2-(1-naphthylmethyl)-3-(dimethylcarbamoyl)propionyl]-L-histidine azide. The cold azide solution was added dropwise to a solution of 50 mg of methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride and 0.04 ml of triethylamine in 5 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 dried over anhydrous magnesium sulfate and evaporated reduced pressure. The residue was purified by preparative silica gel thin layer chromatography (developing solvent: a lower layer of chloroform/methanol/water=8/3/1, Rf1 = 0.69) to obtain 20 mg of methyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(dimethylcarbamoyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexanoate as a white powder.

Provenance & Evidence