Synthesis
General procedure for the synthesis of 1,3-dibromoisoquinoline from 1,3-[2H,4H]-isoquinolinedione: A mixture of 1,3-[2H,4H]-isoquinolinedione (20a, 0.65 g, 4.02 mmol), phosphorus tribromide (1.51 mL, 16.05 mmol) and phosphorus tribromide (1.04 g, 3.61 mmol) was reacted at 180°C The reaction was stirred for 2 hours. Upon completion of the reaction, the mixture was cooled to room temperature, slowly poured into ice water and the pH was adjusted to 8-9 with aqueous 2 N potassium hydroxide. subsequently, the aqueous layer was extracted with toluene and the organic layer was filtered through a neutral alumina column. Finally, the filtrate was evaporated to give the title compound 1,3-dibromoisoquinoline (0.58 g, 56% yield) as a white solid.LRMS (m/z): 286/288/290 (M + 1)+.1H NMR (400 MHz, chloroform-d) δ ppm: 7.67-7.76 (m, 3H), 7.84 (s, 1H), 8.24 (d, J = 8.40 Hz, 1H).
References
[1] Patent: US6340759, 2002, B1. Location in patent: Example 28
[2] Patent: WO2012/41476, 2012, A1. Location in patent: Page/Page column 56-57
[3] Patent: EP2441755, 2012, A1. Location in patent: Paragraph 0172
[4] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 17, p. 5891 - 5908
