Methyl triflate → dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate

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A solution of 2-chloro-6-fluoro-N-{[4-cyclopropylmethylpiperidin-4-yl]methyl}benzamide (I-4) in acetonitrile (2.5 mL) was added to a solution of 2,3-dimethyl-1-[(2-methyl-1H-imidazol-1-yl)sulfonyl]-1H-imidazol-3-ium trifluoromethanesulfonate (for synthesis see J. Org. Chem., 2003, 68, 115) (361 mg, 0.925 mmol) in acetonitrile (2 mL) The yellow solution was stirred at room temperature for 12 h then the solvent removed in vacuo. Biotage chromatography (2% methanol-DCM) afforded 2-chloro-N-{[4-cyclopropylmethyl)-1-[(2-methyl-1H-imidazol-1-ylsulfonyl)]-piperidin-4-yl]methyl}6-fluoro-benzamide (144 mg) that was directly methylated. A solution of methyl triflate (0.031 mL, 0.27 mmol) in DCM (1 mL) was added dropwise to a stirred solution of 2-chloro-N-{[4-cyclopropylmethyl)-1-[(2-methyl-1H-imidazol-1-ylsulfonyl)]-piperidin-4-yl]methyl}6-fluoro-benzamide (118 mg) in DCM (2 mL) cooled in an ice bath. The solution was stirred in an ice bath for 1.5 h then the volatile components removed in vacuo to leave 1-{[4-{[2-chloro-6-fluorobenzoyl)amino]methyl}-4-(cyclopropylmethyl)piperidin-1-yl]sulfonyl}-2,3-dimethyl-1H-imidazol-3-ium trifluoromethanesulfonate (I-5) that was used in the next step without further purification. MS 483 (M+).

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