Tris(hydroxymethyl)aminomethane → 3-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-4-{[4-(2-{3-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]ureido}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 (60 mg) in dichloromethane (3 mL) were added triethylamine (0.016 mL) and 4-nitrophenyl chloroformate (21 mg), and the mixture was stirred at room temperature for 1 hour. To the reaction mixture were added tris(hydroxymethyl)-aminomethane (35 mg) and methanol (3 mL), and the mixture was stirred at room temperature for 3 hours. The reaction mixture was poured into water, and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: dichloromethane/methanol=10/1-6/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(2-{3-[2-hydroxy-1,1-bis(hydroxymethyl)ethyl]ureido}ethoxy)-2-methylphenyl]methyl}-5-isopropyl-1H-pyrazole (36 mg). This material was dissolved in methanol (2 mL). To the solution was added sodium methoxide (28% methanol solution, 0.018 mL), and the mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was purified by solid phase extraction on ODS (washing solvent: distilled water, eluent: methanol) to give the title compound (22 mg).

Provenance & Evidence