Dimethyl Sulfoxide → 4-[4-(2-hydroxy-1,1-dimethylethoxy)phenyl]-6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propylpyrazolo[1,5-a]pyrimidin-5(4H)-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 4′-[(5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (0.68 g), {4-[2-(acetyloxy)-1,1-dimethylethoxy]phenyl}boronic acid (0.94 g), copper(II) acetate (0.68 g), pyridine (2.0 mL), triethylamine (1.0 mL), molecular sieves 4A (2.00 g) and tetrahydrofuran (20 mL) was stirred at room temperature for 1 day. To the reaction mixture was added ethyl acetate (100 mL), and the mixture was stirred at room temperature for 1 hr, and the insoluble material was filtered off. The filtrate was concentrated, and the residue was purified by silica gel column chromatography to give 2-(4-{6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}phenoxy)-2-methylpropyl acetate as a colorless oil (0.85 g, 80%). A mixture of hydroxylammonium chloride (1.55 g), sodium hydrogen carbonate (2.50 g) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 2-(4-{6-[(2′-cyanobiphenyl-4-yl)methyl]-5-oxo-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-4(5H)-yl}phenoxy)-2-methylpropyl acetate (0.85 g) was added, and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (15 mL). N,N′-Carbonyldiimidazole (0.36 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.33 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.25 g, 28%).

Provenance & Evidence