[Synthesis]
Trimethylcyanosilane (52.0 mL, 580.0 mmol) was slowly added dropwise to a stirred solution of compound A2 (65.0 g, 290.0 mmol) and 1,8-diazabicycloundec-7-ene (DBU, 50.0 mL, 348.0 mmol) in tetrahydrofuran (THF, 500 mL) over a period of 15 min at room temperature. The reaction mixture was continued to be stirred at room temperature for 1 hour. Upon completion of the reaction, water was added to the mixture and extracted with dichloromethane (DCM). The organic layers were combined, dried over anhydrous sodium sulfate (Na2SO4) and subsequently concentrated under reduced pressure to give the crude product. The crude product was purified by silica gel column chromatography (100-200 mesh) with the eluent being a gradient solution of 0-4% ethyl acetate (EtOAc) in petroleum ether, which resulted in the target compound 6-bromoisoquinoline-1-carbonitrile (A3) as a white solid in 41 g (61% yield). Thin layer chromatography (TLC) showed an Rf value of 0.6 (30% EtOAc in petroleum ether solution). Liquid chromatography-mass spectrometry (LCMS) analysis showed m/z = 233 ([M + H]+). Nuclear magnetic resonance hydrogen spectroscopy (1H NMR, 400 MHz, DMSO-d6) data were as follows: δ 8.07 (dd, J = 11.2, 2.0 Hz, 1H), 8.21 (m, 2H), 8.55 (br s, 1H), 8.77 (d, J = 7.6 Hz, 1H). |