General procedure for the synthesis of 2-amino-3-(difluoromethoxy)-5-bromopyridine from 3-(difluoromethoxy)pyridin-2-amine: N-bromosuccinimide (2.61 g, 14.65 mmol) was slowly added to an acetonitrile solution (15 mL) of 3-(difluoromethoxy)pyridin-2-amine (2.3 g, 14.36 mmol) over a period of 3 min at 0 °C ) in acetonitrile. The reaction mixture was continued to be stirred at the same temperature for 20 minutes. Subsequently, the reaction solution was concentrated to dryness in vacuo and the resulting viscous material was diluted with water and extracted with ethyl acetate (3 x 60 mL). The organic layers were combined, dried with anhydrous sodium sulfate and concentrated again to dryness. The residue was purified by column chromatography (silica gel, 100-200 mesh, 20% hexane solution of ethyl acetate as eluent) to afford the target product 5-bromo-3-(difluoromethoxy)pyridin-2-amine (3.2 g, 93% yield). The product was confirmed by NMR hydrogen spectrum (400 MHz, DMSO-d6): δ 7.89 (s, 1H), 7.51 (s, 1H), 7.16 (t, J = 73.6 Hz, 1H), 6.34 (s, 2H).
