Potassium Carbonate → HCID 67376178, compound

Participants

Reaction Conditions

Reaction Steps

In a sealed microwave vial under nitrogen, a mixture of 4-(4-bromo-2-fluorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (124 mg, 0.303 mmol), bis(pinacolato)diboron (81 mg, 0.318 mmol), potassium acetate (89 mg, 0.909 mmol) and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (12.37 mg, 0.015 mmol) in 1,4-dioxane (2.5 mL) was stirred at 100° C. in an oil bath for 1 h. The reaction was cooled to room temperature. Analysis by LCMS showed complete conversion to the boronic ester intermediate (boronic ester cleavage to acid also observed on LCMS due to water/TFA conditions). 3-Bromobenzophenone (79 mg, 0.303 mmol) and 2M aq potassium carbonate (0.45 mL, 0.909 mmol) were added to the reaction mixture. The resultant reaction mixture was stirred at 100° C. in an oil bath for 1 h. The reaction was cooled to room temperature. The reaction mixture was then transferred to a separatory funnel and the layers were separated. The aqueous layer was adjusted to pH˜5 using 1N aq HCl and then extracted with ethyl acetate (2×50 mL). The organic layers were combined, dried over MgSO4, and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-5% methanol/ethyl acetate) provided the desired product as a white solid, which was dried in a vacuum oven (70° C.) overnight. The solid was further purified by reverse phase HPLC (10-80% acetonitrile/water+0.1% NH4OH). The desired product was dissolved in acetonitrile (2 mL) and water (10 mL), frozen, and lyophilized over the weekend. The solid was further dried in a vacuum oven (70° C.) overnight to give the title compound as a white solid (72 mg, 46%). MS(ES)+ m/e 511.1 [M+H]+.

Provenance & Evidence