7-BROMO-1-HYDROXYISOQUINOLINE

To a solution of 7-bromo-1-chloroisoquinoline 1a (2.70 g, 11.10 mmol) in acetic acid (50 mL) was addedammonium acetate 1b (8.50 g, 111.10 mmol). Reaction mixture was stirred at 100°C for 4 h. The reaction mixture wasconcentrated in vacuo, and to the residue was added water. The precipitate was collected by filtration and washed withwater to give 7-bromoisoquinolin-1(2H)-one 1c (2.7 g, white solid). The product was used in the next step directly withoutpurification.MS m/z (ESI): 225.9 [M+1]1H NMR (400 MHz, CDCl3) δ 8.55 (d, J = 1.8 Hz, 1H), 7.75 (dd, J = 2.1, 8.5 Hz, 1H), 7.43 (d, J = 8.6 Hz, 1H), 7.14 (d, J = 6.2 Hz, 1H), 6.52 (d, J = 7.3 Hz, 1H)Compound WXBB-5-1 (5.00 g, 22.32 mmol, 1.00 eq) and 1-chloromethyl-4-fluoro-1, 4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (8.70 g, 24.55 mmol, 1.10 eq) were dissolved in acetonitrile (200.00 mL) and water (3.00 mL). The mixture was reacted at 20 C. for 96 hours. The reaction solution was added with water (300 mL), and extracted with dichloromethane (DCM) (300 mL). The organic phases were combined, washed with saturated brine (30 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate was dried on a rotary evaporator under reduced pressure. The obtained crude product was slurried with ethyl acetate (20 mL) at 15 C. for 0.5 hour, filtered and the filter cake was dried. Compound WXBB-5-2 (3.00 g, 11.54 mmol, 51.68% yield) was obtained as a yellow solid, 1H NMR (400 MHz, DMSO-d6) delta ppm 3.11 (d, J=6.78 Hz, 1H) 3.36 (br. s., 1H) 5.07 (d, J=4.27 Hz, 1H) 5.75-5.98 (m, 1H) 7.44 (d, J=8.03 Hz, 1H) 7.79-8.04 (m, 3H) 8.87 (br. s., 1H).C. 7-Bromo-1-chloroisoquinoline B.