Synthesis
To a stirred solution of 3-bromoisoquinoline (Intermediate-12) (9.2 g, 44.2 mmol) in N,N-dimethylformamide (DMF) (15 mL) was sequentially added tetrakis(triphenylphosphine)palladium (Pd(PPh3)4) (10.2 g, 8.84 mmol) and zinc cyanide (Zn(CN)2) (10.34 g, 88.44 mmol. 2.0 equiv). The reaction system was degassed with nitrogen (N2) for 20 min to exclude oxygen. Subsequently, the reaction mixture was heated to 120 °C and the reaction was stirred at this temperature overnight. The progress of the reaction was monitored by thin layer chromatography (TLC) and after confirming the completion of the reaction, the reaction mixture was cooled to room temperature. Insoluble impurities were removed by filtration and the filtrate was concentrated under reduced pressure to remove solvent. The resulting crude product was purified by fast column chromatography (eluent: 10% ethyl acetate/hexane) to afford the target compound 4-cyanoisoquinoline (3.4 g, 27.4% yield) as a pale yellow solid.
