General procedure for the synthesis of methyl methyl 3-bromopyrazine-2-carboxylate from methyl 3-aminopyrazine-2-carboxylate: bromine (3.91 g, 24.46 mmol) was added slowly and dropwise at 0 °C to a stirred mixture containing methyl 3-aminopyrazine-2-carboxylate (1.27 g, 8.29 mmol) and hydrobromic acid (4.70 mL, 41.5 mmol). . Subsequently, a solution of sodium nitrite (1.44 g, 20.9 mmol) dissolved in water (6 mL) was added dropwise. The reaction mixture was continued to be stirred at 0 °C for 15 min. Upon completion of the reaction, the pH was adjusted to 8 with saturated aqueous sodium bicarbonate solution, followed by extraction with ethyl acetate (80 mL) and chloroform (50 mL). The organic phases were combined, dried with anhydrous magnesium sulfate, and concentrated under reduced pressure to afford 1.13 g (63% yield) of an orange oil, which solidified to the target product, methyl methyl-3-bromopyrazine-2-carboxylate, upon standing.
