Cesium carbonate → 4-[4-(1-benzofuran-5-yl)-2,5-difluorophenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Participants

Reaction Conditions

Reaction Steps

To a microwave vial were added 4-(4-bromo-2,5-difluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (50 mg, 0.117 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-benzofuran (42.8 mg, 0.176 mmol), cesium carbonate (114 mg, 0.351 mmol), and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (6.0 mg, 0.00735 mmol). The mixture was purged with nitrogen followed by the addition of 1,4-dioxane (1 mL) and water (0.5 mL). The suspension was heated overnight at 100° C. and analysis by LCMS indicated desired product formation and consumption of starting material. The mixture was filtered through a syringe filter and purified by reverse phase HPLC (10-90% acetonitrile/water+0.1% TFA). The desired fractions were collected and added to a separatory funnel containing ethyl acetate. The aqueous phase was adjusted to pH˜6 with 1N aq HCl. The aqueous phase was extracted with ethyl acetate (3×), and the combined organics were washed with brine, dried over Na2SO4 and concentrated in vacuo to afford the title product as a white solid (25 mg, 46%). MS(ES)+ m/e 465.2 M+H]+.

Provenance & Evidence