Potassium Carbonate → 5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-4-[2-fluoro-4-(6-fluoro-2-naphthalenyl)phenyl]-2,4-dihydro-3H-1,2,4-triazol-3-one

Participants

Reaction Conditions

Reaction Steps

Into a 5 mL microwaveable vial was placed 4-(4-bromo-2-fluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (0.244 mmol), bis(pinacolato)diboron (0.244 mmol), potassium acetate (0.977 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II)-dichloromethane adduct (0.024 mmol), and 1,4-dioxane (2 mL). The vial was capped and the contents were purged with nitrogen. The solution stirred at 100° C. for 16 h. LCMS analysis displayed boronic ester intermediate present (boronic ester cleavage to acid also observed on LCMS) as well as a small amount of bromide starting material. The reaction was cooled to room temperature. Added to the vial was 2-bromo-6-fluoronaphthalene (0.244 mmol) and 2M aq potassium carbonate (1 mL). The vial was capped, purged with nitrogen, and stirred at 100° C. for 1 h. The solution was cooled to room temperature, whereby the dioxane layer separated from the aqueous layer. The dioxane layer was removed via pipette and was passed through a plug of celite and sodium sulfate. The plug was washed with dioxane (2 mL). All dioxane filtrates were combined and concentrated in vacuo. Reverse phase HPLC (30-80% acetonitrile/water+0.1% NH4OH) was utilized in purifying the title compound (21 mg, 17%). MS(ES)+ m/e 475.1 [M+H]+.

Provenance & Evidence