Potassium Phosphate, Tribasic → 4'-(3-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)-4-biphenylcarbonitrile

Participants

Reaction Conditions

Reaction Steps

A vial was charged with a slurry of 4-(4-bromophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (100 mg, 0.256 mmol), (4-cyanophenyl)boronic acid (75 mg, 0.511 mmol), tetrakis(triphenylphosphine)palladium(0) (29.5 mg, 0.026 mmol) and tripotassium phosphate (217 mg, 1.022 mmol) in ethanol (4.0 mL) and water (4.00 mL) then purged with nitrogen and sealed with a standard teflon septa (crimped aluminum seal). The reaction was then heated in an aluminum block at 110° C. for 2 h. The resulting yellow slurry was diluted with ethanol, treated with silica powder (2 g) then evaporated under reduced pressure. The dried powder was placed in a column adaptor (Analogix Dasi adapter) attached to a standard stock silica column (Analogix SF25-40 g) and eluted with ethyl acetate for 10 min and then with 7% methanol in dichloromethane. The combined desired fractions were evaporated to a colorless oil that was crystallized from hexanes/ethyl acetate to afford the title compound as a white solid (30 mg, 28.1%). MS(ES)+ m/e 414.2 [M+H]+.

Provenance & Evidence