Hydrochloric Acid → HCID 178501835, compound

Participants

Reaction Steps

To a suspension of 200 mg of N-[2-(1-naphthylmethyl)-3-(piperidinocarbonyl)propionyl]-L-histidine hydrazide in 2 ml of dry N,N-dimethylformamide were added successively 0.26 ml of a dry 5.1N-hydrogen chloride in N,N-dimethylformamide solution and 0.066 ml of isoamyl nitrite with stirring at -20° C. After disappearance of hydrazide compound, the reaction mixture was cooled to -30° C. and neutralized with 0.19 ml of triethylamine to prepare a solution of N-[2-(1-naphthylmethyl)-3-(piperidinocarbonyl)propionyl]-L-histidine azide. The cold azide solution was added dropwise to a solution of 88 mg of methyl (2RS, 3S)-3-amino-2-hydroxy-5-methylhexanoate hydrochloride and 0.058 ml of triethylamine in 2 ml of dry N,N-dimethylformamide with stirring under ice-cooling, and then 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 separated by silica gel flash column chromatography (eluent: chloroform/methanol=20/1 by volume), and fractions containing desired product which has Rf1 value of 0.54 were combined to obtain 141 mg of methyl (2RS, 3S)-3-{N-[2-(1-naphthylmethyl)-3-(piperidinocarbonyl)propionyl]-L-histidyl}amino-2-hydroxy-5-methylhexanoate as a white powder.

Provenance & Evidence