Synthesis
General procedure for the synthesis of 5-nitroisoquinoline from isoquinoline:
1. dissolve isoquinoline (3.0 g, 23.2 mmol) in 40 mL of concentrated sulfuric acid at -15 °C and slowly add solid potassium nitrate (2.8 g, 27.8 mmol) in four equal portions, each at 30 min intervals.
2. The reaction mixture was gradually warmed to room temperature and stirring was continued for 3 hours.
3. The reaction mixture was poured into ice water (100 mL) and the pH was adjusted to 8-10 with ammonia.
4. The precipitated yellow solid was collected by filtration, washed with methyl tert-butyl ether (100 mL x 2) and dried to give 5-nitroisoquinoline (4.0 g, 100% yield).
5. 5-Nitroisoquinoline (2.5 g, 14.4 mmol) was dissolved in methanol (50 mL), 10% palladium/carbon catalyst (300 mg) was added, and stirred at room temperature for 3 hours under hydrogen atmosphere.
6. The reaction mixture was filtered and the filtrate was concentrated in vacuum to give 5-aminoisoquinoline (0.85 g, 41% yield) as a brown solid.
References
[1] Bioorganic Chemistry, 2019, vol. 82, p. 100 - 108
[2] Patent: WO2012/146724, 2012, A2. Location in patent: Page/Page column 49
[3] Patent: US2014/57942, 2014, A1. Location in patent: Paragraph 0337-0338
[4] Patent: WO2014/68035, 2014, A1. Location in patent: Page/Page column 35
[5] Journal of Organic Chemistry, 1986, vol. 51, # 11, p. 2011 - 2021
