Synthesis
General procedure for the synthesis of 4-bromo-1(2H)-isoquinolinone from 1-hydroxyisoquinoline: N-bromosuccinimide (NBS, 142 mg, 0.796 mmol) was added to a solution of DMF (2 mL) containing isoquinolin-1(2H)-one (105 mg, 0.723 mmol). The reaction mixture was stirred at room temperature for 2 hours. After completion of the reaction, the mixture was concentrated to remove the solvent. The crude product was purified by preparative high performance liquid chromatography (HPLC) to afford the intermediate 6 4-bromoisoquinolin-1(2H)-one (110 mg, 68% yield). [C] MS (ESI) m/z: 223.9 (M + H)+. 1H NMR (500 MHz, DMSO-d6) δ 11.57 (br.s, 1H), 8.24 (dd, J = 8.0, 0.8 Hz, 1H), 7.88-7.83 (m, 1H), 7.79-7.75 (m, 1H), 7.61 (ddd, J = 8.0, 7.1, 1.1 Hz, 1H), 7.55 (s, 1H).
References
[1] Journal of Medicinal Chemistry, 2014, vol. 57, # 4, p. 1299 - 1322
[2] Angewandte Chemie - International Edition, 2011, vol. 50, # 36, p. 8416 - 8419
[3] Synthetic Communications, 2007, vol. 37, # 23, p. 4199 - 4208
[4] Patent: US2014/206686, 2014, A1. Location in patent: Paragraph 0497-0499
[5] Patent: WO2016/69976, 2016, A1. Location in patent: Page/Page column 91
