Uses
5-Bromo-1-chloroisoquinoline can be used as an organic synthesis intermediate, and there are literature reports that it can be used to prepare 5-benzylisoquinoline derivatives for the treatment of cardiovascular diseases.
Synthesis
General procedure for the synthesis of 5-bromo-1-chloroisoquinoline from 5-bromoisoquinoline: To a solution of 5-bromoisoquinoline (60 g, 288 mmol) in dichloromethane (1.5 L) was added 75% m-chloroperoxybenzoic acid (m-CPBA, 75 g, 436 mmol). The reaction mixture was heated and stirred at 40°C for 20 hours. Upon completion of the reaction, the progress of the reaction was confirmed by HPLC monitoring, and after the reaction mixture was cooled to room temperature, sodium thiosulfate (75 g) was added within 10 min, followed by water (300 mL). The organic phase was separated, washed with 1N sodium hydroxide solution and then dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give a white solid (42 g), which could be used directly in the next step of the reaction. The intermediate (37 g, 165 mmol) obtained above was dissolved in dichloromethane (900 mL), trichlorophosphorus (POCl3, 37 mL) was added, and the reaction was stirred for 18 hours at 45 °C. Upon completion of the reaction, the progress of the reaction was confirmed by HPLC and/or GC monitoring and the reaction mixture was concentrated under reduced pressure. The residue was carefully treated with water and the aqueous phase was extracted with dichloromethane. The organic phases were combined and washed sequentially with saturated sodium bicarbonate solution and saturated sodium chloride solution. Evaporation of the solvent under reduced pressure afforded the beige solid intermediate 5-bromo-1-chloroisoquinoline (33 g), which can be used directly in the next step of the reaction. The structure of the product was confirmed by 1H NMR (400 MHz, CDCl3) and GC-EI (70eV): 1H NMR δ 8.35 (2d, 2H), 8.00 (2d, 2H), 7.55 (t, 1H); GC-EI (70eV): M+. = 241.
References
[1] Patent: US2013/296320, 2013, A1
[2] Patent: WO2016/201052, 2016, A1
[3] Patent: US2017/137385, 2017, A1. Location in patent: Paragraph 0203; 0204; 0205; 0206
