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

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To a solution of 4-[4-(1-benzofuran-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (85 mg, 0.198 mmol) in N,N-dimethylformamide (1 mL) in a 5 mL microwaveable vial was added potassium carbonate (55 m mg, 0.398 mmol, 2 eq) and methyl iodide (2M in t-butylmethyl ether, 0.100 mL, 1 eq). The reaction vial was capped, purged with nitrogen gas, and stirred for 16 h at 80° C. Analysis by LC/MS displayed the reaction had progress by 70%. An additional 0.050 mL of 2M solution of methyl iodide was added and the reaction mixture was stirred at 80° C. for 6 h. Analysis by LC/MS displayed the reaction had progress by 95%. The reaction mixture was cooled to room temperature and then poured into a mixture of dichloromethane and water. The organic layer was separated. The aqueous layer was washed with dichloromethane. The organic extracts were combined and washed 3× with a dilute brine solution. The organic layer was separated, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude product was purified by reverse phase HPLC (LUNA C-18: 30×50 mm column; 23-55% acetonitrile w/0.1% TFA/water w/0.1% TFA). The product fractions were neutralized with the addition of saturated aq sodium bicarbonate, combined, and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo to afford the title compound (37 mg, 42%). MS(ES)+ m/e 443.2 [M+H]+.

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