Acetonitrile → 1-{[3-fluoro-2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-3-[2-(4-methoxyphenyl)-2-oxoethyl]-6-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-[2-(4-methoxyphenyl)-2-oxoethyl]-6-methylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione (1 g), 4′-(bromomethyl)-3′-fluorobiphenyl-2-carbonitrile (1.06 g), potassium carbonate (0.84 g) and acetonitrile (50 mL) was stirred at 50° C. for 2 hr. Insoluble material was filtered off, and the obtained filtrate was concentrated under reduced pressure. The obtained residue was dissolved in dimethyl sulfoxide (5 mL), and added to a mixture of hydroxylammonium chloride (1.81 g), sodium hydrogencarbonate (2.73 g) and dimethyl sulfoxide (20 mL), which had been stirred at 40° C. for 30 min in advance. The reaction mixture was stirred at 90° C. for 16 hr, diluted with chloroform, washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography and dissolved in methylene chloride (40 mL). N,N′-Carbonyldiimidazole (0.42 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.36 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with chloroform, washed successively with saturated aqueous potassium hydrogensulfate solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. To the obtained residue were added 20% sulfuric acid (5 mL) and ethanol (20 ml). The mixture was stirred at 100° C. for 1 hr, and extracted with chloroform and water. The chloroform layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.51 g, 39%).

Provenance & Evidence