Water → HCID 86723904, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(5-(4-bromo-1-(4-cyanophenyl)-1H-pyrazol-5-yl)-4-methyl-2,6-dioxo-3-(3-(trifluoromethyl)phenyl)-2,3-dihydropyrimidin-1(6H)-yl)ethyl acetate (prepared in Example 98) (220.3 mg) in dimethoxyethane (4.0 ml) were added isopropenyl boronic acid pinacol ester (69.0 μl), tetrakis(triphenylphosphine)palladium (85.2 mg), sodium carbonate (194.3 mg) and water (0.4 ml) and the resulting mixture was stirred at 100° C. for seven hours. To the reaction mixture was added ethyl acetate (100 ml) and the mixture was washed with water (30 ml) and saturated saline (30 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. To a solution of the residue in methanol (4 ml) was added palladium carbon (28.7 mg) and the resulting mixture was stirred at room temperature under hydrogen atmosphere for six hours. The reaction mixture was filtered through Celite (trade mark) and then concentrated under reduced pressure. To a solution of the residue in methanol (5 ml) was added under ice-cooling 1M aqueous potassium carbonate solution (392 μl) and the resulting mixture was stirred under ice-cooling for one hour. To the reaction mixture was added 1M hydrochloric acid (329 μl) and the mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: toluene/ethyl acetate) to afford 4-(5-(3-(2-hydroxyethyl)-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-4-isopropyl-1H-pyrazol-1-yl)benzonitrile (62.6 mg) as white solid.

Provenance & Evidence