Synthesis
General procedure for the synthesis of 4-bromo-5-nitroisoquinoline (11) from 4-bromoisoquinoline: potassium nitrate (5.34 g, 0.052 mol) was slowly added to 20 mL of concentrated sulfuric acid and dissolved by careful heating. The resulting solution was added dropwise to a solution of 4-bromoisoquinoline (10 g, 0.048 mol) dissolved in 40 mL of the same acid at 0 °C. After removing the cooling bath, the reaction mixture was stirred at room temperature for 1 hour. Subsequently, the reaction mixture was poured into crushed ice (400 g) and adjusted to alkaline with ammonium hydroxide. The resulting yellow precipitate was collected by filtration and the filtrate was extracted with ether (3 x 500 mL), dried over anhydrous sodium sulfate and concentrated to give a yellow solid. This solid was combined with the initial precipitate and recrystallized from methanol to give 12.1 g (89% yield) of 4-bromo-5-nitroisoquinoline (11) as light yellow crystals.
References
[1] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 6, p. 1403 - 1412
[2] Patent: WO2006/12640, 2006, A2. Location in patent: Page/Page column 43
[3] Patent: US2007/155720, 2007, A1. Location in patent: Page/Page column 20
[4] Patent: US2002/132827, 2002, A1
[5] Patent: US6413977, 2002, B1
