The general procedure for the synthesis of 3,6-dibromo-2,4-dimethylpyridine starting from 2-amino-5-bromo-4,6-dimethylpyridine was as follows: 2-amino-5-bromo-4,6-dimethylpyridine (201 mg, 1 mmol) was dissolved in 48% hydrobromic acid (3 mL) at 0 °C, and slowly added dropwise to sodium nitrite (172 mg, 2.5 mmol) in an aqueous solution (0.6 mL). The reaction mixture was stirred at 0-5 °C for 30 min, then bromine (448 mg, 2.8 mmol) was added and the reaction temperature was ensured not to exceed 5 °C. The reaction mixture was stirred at 0-5 °C for 30 min. After continued stirring for 30 min, the reaction mixture was adjusted to alkaline with 20% cold sodium hydroxide solution. Subsequently, it was extracted three times with ethyl acetate, the organic layers were combined and dried with anhydrous sodium sulfate, filtered and concentrated. Finally, the residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate, 10:1) to afford the light yellow solid product 3,6-dibromo-2,4-dimethylpyridine (243 mg, 92% yield).
