1,1'-Carbonyldiimidazole → 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)-N-(tetrahydro-2H-pyran-2-yloxy)picolinamide

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1,1′-Carbonyl diimidazole (110 mg, 0.66 mmol, 1.1 equiv) was added to a stirred suspension of 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)picolinic acid (200 mg, 0.60 mmol, 1.0 equiv) in THF (3.0 mL) at 23° C. The resulting off-white suspension was stirred at 23° C. for 30 min O-(Tetrahydro-2H-pyran-2-yl)hydroxylamine (85 mg, 0.72 mmol, 1.2 equiv) was added and the off-white suspension was stirred at 23° C. for 18 h. The reaction mixture was concentrated by a nitrogen stream, and the residue was directly subjected to silica gel column chromatography (5% methanol in chloroform) to afford a white powder (180 mg, 69%): mp 176-179° C.; 1H NMR (300 MHz, DMSO-d6) δ 7.66 (t, J=8 Hz, 1H), 7.42 (dd, J=2, 8 Hz, 1H), 7.20 (d, J=2 Hz, 1H), 6.75 (br s, 2H), 5.01 (m, 1H), 4.05-3.90 (m, 4H), 3.50 (m, 1H), 1.77-1.66 (m, 3H), 1.60-1.47 (m, 3H); IR (neat film) 3325 (w), 3198 (w), 2946 (m), 2873 (w), 1682 (s), 1634 (s) cm−1; ESIMS m/z 430.3 ([M+H]+).

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