Triphenylphosphine → 3-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyloxy)-5-isopropyl-4-{[4-(3-{N-(2-nitrobenzenesulfonyl)-N-[1-carbamoyl-1-(methyl)ethyl]amino}propoxy)-2-methylphenyl]-methyl}-1H-pyrazole

Participants

Reaction Steps

To a solution of 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-{[4-(3-hydroxypropoxy)-2-methylphenyl]-methyl}-5-isopropyl-1H-pyrazole (0.25 g) in tetrahydrofuran (2 mL) were added 2-methyl-2-(2-nitrobenzenesulfonylamino)propionamide (0.14 g), triphenylphosphine (0.12 g) and diethyl azodicarboxylate (40% toluene solution, 0.26 mL), and the mixture was stirred at room temperature overnight. The reaction mixture was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/4-dichloromethane/methanol=20/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-5-isopropyl-4-{[4-(3-{N-(2-nitrobenzenesulfonyl)-N-[1-carbamoyl-1-(methyl)ethyl]amino}propoxy)-2-methylphenyl]-methyl}-1H-pyrazole (0.32 g). This material was dissolved in acetonitrile (3 mL). To the solution were added cesium carbonate (0.46 g) and thiophenol (0.038 mL), and the mixture was stirred at room temperature for 1 hour. 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 successively, and dried over anhydrous sodium sulfate. The solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel (eluent: n-hexane/ethyl acetate=1/5-dichloromethane/methanol=15/1-10/1) to give 3-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyloxy)-4-[(4-(3-[1-carbamoyl-1-(methyl)ethylamino]propoxy)-2-methylphenyl)methyl]-5-isopropyl-1H-pyrazole (20 mg). This material was dissolved in methanol (1 mL). To the solution was added sodium methoxide (28% methanol solution, 0.01 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 (11 mg).

Provenance & Evidence