1-Hydroxybenzotriazole → 3-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-[(4-{2-[2-{[4-(benzyloxycarbonyl)piperazin-1-yl]-carbonyl}-2-(methyl)propionylamino]ethoxy}-2-methylphenyl)-methyl]-5-isopropyl-1H-pyrazole

Participants

Reaction Steps

To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(2-aminoethoxy)-2-methylphenyl]methyl}-5-isopropyl-1H-pyrazole (0.5 g) in N,N-dimethylformamide (10 mL) were added 1-benzyloxycarbonyl-4-[2-carboxy-2-(methyl)propionyl]piperazine (0.28 g), 1-hydroxybenzotriazole (0.22 g), triethylamine (0.18 mL) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.46 g), and the mixture was stirred at room temperature for 2 days. The reaction mixture was poured into water, and the resulting mixture was extracted with diethyl ether. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution, water and brine successively, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=30/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-[(4-{2-[2-{[4-(benzyloxycarbonyl)piperazin-1-yl]-carbonyl}-2-(methyl)propionylamino]ethoxy}-2-methylphenyl)methyl]-5-isopropyl-1H-pyrazole (0.3 g). This material was dissolved in methanol (4 mL). To the solution was added sodium methoxide (28% methanol solution, 0.06 mL), and the mixture was stirred at room temperature for 30 minutes. To the reaction mixture was added acetic acid (0.035 mL), and the resulting mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1-5/1) to give the title compound (0.23 g).

Provenance & Evidence