Trifluoroacetic anhydride → 4-cyano-3-(methoxycarbonyl)-2-(1-methyl-1H-pyrazol-4-yl)pyridine 1-oxide

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Reaction Steps

To a mixture of methyl 4-cyano-2-(1-methyl-1H-pyrazol-4-yl)nicotinate (470 mg, 1.940 mmol) in DCM (10 mL) was added urea-hydrogen peroxide compound (1/1, 913 mg, 9.70 mmol), and 2,2,2-trifluoroacetic anhydride (1.370 mL, 9.70 mmol) at 0° C. The mixture was stirred at room temperature for 4 h. More urea-hydrogen peroxide compound (1/1, 400 mg) was added and the mixture was stirred at RT for an additional 3 h after which was added saturated aq NaHCO3 solution and CHCl3. The aqueous phase was extracted with CHCl3 (3×), and the combined organic layers were washed with brine, dried over MgSO4, and evaporated to obtain crude 4-cyano-3-(methoxycarbonyl)-2-(1-methyl-1H-pyrazol-4-yl)pyridine 1-oxide, which was combined with phosphorus oxychloride (2 mL, 21.46 mmol). The resulting mixture was stirred at 80° C. for 5 h and then concentrated to a residue, which was neutralized with 2N NaOH. The organic phase was washed with brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2(Hexane/EtOAc=1/1) to give the title compound as a white solid (155 mg, 41.3%). 1H NMR (500 MHz, CDCl3) δ ppm 3.96 (s, 3 H), 4.03 (s, 3 H), 7.41 (s, 1 H), 7.81 (s, 1 H), 7.94 (s, 1 H). [M+H] calc'd for C12H9ClN4O2, 277; found, 277.

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