In 4 mL screwcap vial was placed 4-(4-bromophenyl)-5-[(3S)-3-pyrrolidinylmethyl]-2,4-dihydro-3H-1,2,4-triazol-3-one hydrochloride (0.417 mmol) and 1 mL dichloromethane. N,N-Diisopropylethylamine (1.374 mmol) was added. The vial contents were stirred for 1 min. In a separate vial, acetyl chloride (0.417 mmol) was diluted with 1 mL dichloromethane and added to the prior solution dropwise via pipette. The vial was capped and the reaction was stirred at room temperature overnight. Analysis by LCMS displayed the reaction had only progressed to 70% completion. A solution of acetyl chloride (0.050 mL) in 1 mL dichloromethane was prepared and 0.100 mL of this solution was added to the reaction. After 1 h, the reaction had progressed to 90% completion via LCMS analysis. Another 0.100 mL of the acetyl chloride solution in dichloromethane was added to the reaction. After 1 h, LCMS analysis displayed the reaction was complete. The solution was washed with saturated aq NH4Cl. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification of the residue by silica gel chromatography (0-20% methanol:ethyl acetate) afforded the title compound (77 mg, 50% yield). MS(ES)+ m/e 365.0, 366.7 [M+H]+.
