Procedure for the synthesis of 5-bromo-4-methyl-2-cyanopyridine: To a solution of 2,5-dibromo-4-methylpyridine (15 g, 59.8 mmol, 1.00 eq.) in N,N-dimethylformamide (DMF, 100 mL) was added sequentially cuprous(I) cyanide (4.28 g, 47.8 mmol, 0.8 eq.) and sodium cyanide (2.34 g, 47.8 mmol, 0.8 equiv). The reaction mixture was heated and refluxed for 20 h, during which precipitation was observed. Upon completion of the reaction, the mixture was cooled to room temperature, water (in appropriate amount) was added and sonicated to promote dispersion of the precipitate. Subsequently, the solid product was collected by filtration and washed with plenty of water to remove residual inorganic salts. The filtrate was extracted with ethyl acetate (EtOAc) and the combined organic layers were washed sequentially with water and saturated saline. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent to obtain the crude product. The crude product was purified by silica gel column chromatography with an eluent gradient of 0-10% ethyl acetate/hexane, and finally 5-bromo-4-methyl-pyridine-2-carbonitrile (5 g, 42.4% yield) was obtained as a white solid.
