3-Cyano-2-methylpyridine

Pale yellow solid

2-Methylnicotinonitrile (133) 30) 2-methyl-nicotinonitrileCyanuric acid (418 mg, 2.2 mmol) was added in one portion to a suspension of 2-methylnicotinamide (intermediate 29) (613 mg, 4.5 mmol) in 2.5 ml of DMF cooled in ice. The 0 reaction was stirred for 2.5 hours then poured into ice. The reaction was extracted with ethyl acetate until the organic layer no longer contained product. The combined organic layers, were dried over Na3-Bromo-2-methylpyridine (344 mg, 2 mmol), Zn(CN)2 (235 mg, 2 mmol) and Pd(PPh3)4 (75 mg, 0.06 mmol) were dissolved in DMF (5 mL). The mixture was vacuumed for N2 three times, The reaction solution was reacted in the microwave (175° C.) for 2 h under N 2 protection. After cooling, it was diluted with EtOAc (60 mL). After washing with saturated saline, dry over anhydrous sodium sulfate. Concentration by filtration and column chromatography of the residue provided the title compound as a white solid (212 mg, yield 90percent).Step 2 30) General procedure: Procedure I: To a mixture of 3-bromo-2, 6-dimethylpyridine (500 mg, 2.69 mmol) in DMF (5 mL), was added CuCN (480 mg, 5.38 mmol). The reaction mixture was stirred at 150 for 12 h. It was then diluted with DCM and washed with aq. NH4Cl (1117) (85%)/NH3.H2O(15%), water and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue was purified by flash column chromatography over silica gel (DCM/MeOH 10:1, v/v) to give 2, 6-dimethylnicotinonitrile as a yellow solid (210 mg, 59%). LC-MS (ESI): m/z (M+1)+ = 133.17.