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2-Chloro-3-methylpyrazine is a pyrazine compound in which the chlorine atom in the structure can be replaced for the preparation of other medicinal chemicals. It is used in the preparation of macrocyclic urea kinase inhibitors.

(i) Chlorine gas was passed into carbon tetrachloride (67 mL) at a constant flow rate for 30 minutes. Subsequently, the resulting yellow solution was slowly added dropwise to a solution of carbon tetrachloride (125 mL) containing pyridine (4.8 mL) and 2-methylpyrazine (5 g) over a period of 30 minutes while stirring was maintained. Upon completion of the reaction, the reaction system was purged with nitrogen to remove residual chlorine gas, followed by removal of volatile solvents by rotary evaporation. The resulting brown oily crude product was purified by silica gel column chromatography using dichloromethane as eluent to give 2-chloro-3-methylpyrazine as a final brown oil (3.62 g, 53% yield). The structure of the product was confirmed by 1H NMR (d6-DMSO): δ 6.59 (s, 2H), 7.67 (d, 1H), 7.94 (d, 1H); the mass spectrum (+ve CI) showed the molecular ion peak m/z 129 ([M + H]+).

[1] Patent: US5861401, 1999, A
[2] Patent: CN107954913, 2018, A. Location in patent: Paragraph 0021