Potassium nitrate (4.87 g, 48.20 mmol) was slowly added to a stirred solution of 3-bromo-2-chloropyridin-4-amine (5.00 g, 24.10 mmol) in concentrated sulfuric acid (36 mL) at about 5 °C. The reaction mixture was gradually warmed to room temperature and stirred continuously for 20 hours. Subsequently, the reaction mixture was slowly poured into crushed ice (~400 mL) and a light yellow precipitate precipitated. The precipitate was collected by filtration and washed with plenty of water. The resulting solid was dried under reduced pressure and added in batches to concentrated sulfuric acid (30 mL), maintaining the temperature at about 5 °C. The reaction mixture was heated to 90 °C and stirred for 2 hours before being cooled to room temperature and allowed to stand for 18 hours. The reaction mixture was again poured into crushed ice (about 400 mL) and a precipitate was precipitated, collected by filtration and washed with cold water. The solid was dissolved in a mixed solvent of methanol and ethyl acetate, and the solution was dried over anhydrous sodium sulfate and concentrated in vacuum to give 3-bromo-2-chloro-5-nitropyridin-4-amine (5.20 g, 85% yield) as a pale orange solid.LCMS (Method I, ESI): retention time = 2.79 min, [M+H]+ = 251.9/253.9/255.9; 1H NMR (400 MHz, DMSO-d6): δ 8.86 (1H, s).
