[Synthesis]
3-Chloro-2-cyanopyridine (44A, 2.59 g, 20 mmol) was used as starting material and mixed with trimethylmethylsilyl cyanide (5.95 g, 60 mmol), triethylamine (Et3N, 4.05 g, 40 mmol), and acetonitrile (20 mL) in a 250 mL three-necked round-bottom flask. The reaction mixture was refluxed under nitrogen protection for 6 h. Complete consumption of raw materials was confirmed by HPLC analysis. Upon completion of the reaction, the cooled reaction mixture was concentrated under reduced pressure to give a brown semi-solid. The semi-solid was extracted by partitioning with 3N Na2CO3 aqueous solution and dichloromethane (CH2Cl2). The organic layer was washed sequentially with water and brine, dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. The resulting residue was purified by fast chromatography using 5% ether (Et2O)/dichloromethane (CH2Cl2) as eluent, and the target product 44B was finally obtained as a white crystalline solid (1.84 g, 67% yield). The structure of the product was confirmed by 1H NMR (CDCl3): δ 7.37 (dd, J = 4.7, 8.4 Hz, 1H), 7.73 (dd, J = 1.4, 8.2 Hz, 1H), 8.47 (dd, J = 1.3, 4.6 Hz, 1H); LC/MS analysis showed m/z 139 [M + H]+. |