Chlorosuccinimide → 3-chloro-4-[(2,4-difluorobenzyl)amino]-1-(2,6-difluorophenyl)-6-methylpyridin-2(1H)-one

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Reaction Steps

1-(2,6-difluorophenyl)-4-hydroxy-6-methylpyridin-2(1H)-one (0.3 g, 1.26 mmol) and 2,4-difluoro benzylamine (1 mL, 84 mmol) were combined in an nitrogen flushed culture tube. The tube was capped and heated at 180 C for 24 h. The excess amine was distilled in vacuo and the residue was used without further purification. N-Chloro succinimide (168 mg, 1.26 mmol) was added to a solution of the residue in methylene chloride (10 mL). After stirring at 25 C for 1 h, the reaction mixture was poured into saturated aqueous NaHCO3. The aqueous mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried with anhydrous Na2SO4, and concentrated in vacuo. The residue was chromatographed on silica (25:75 hexanes:ethyl acetate) to give the title compound (32 mg, 6%). 1H NMR (400 MHz, CD3OD) δ 7.55 (m, 1H), 7.36 (q, J=9.2 and 15.2 Hz, 1H), 7.18 (t, J=7.6 Hz, 2H), 6.98 (m, 2H), 6.15 (s, 1H), 4.62 (s, 2H), 1.96 (s, 3H) ppm. 19F NMR (400 MHz, CD3OD) δ −113.78 (1F), −116.72 (1F), −121.57 (1F) ppm. ES-HRMS m/z 397.0752 (M+H calcd for C19H14ClF4N2O requires 397.0725).

Provenance & Evidence