Synthesis
General procedure for the synthesis of 2-amino-5-bromonicotinaldehyde from 2-amino-3-pyridinecarboxaldehyde:
A. To a solution of 2-aminopyridine-3-carbaldehyde (10.1 g, 81.0 mmol) in acetonitrile (150 mL) was added N-bromosuccinimide (15.1 g, 84.0 mmol). The reaction mixture was stirred under reflux conditions for 2 hours. After completion of the reaction, it was cooled to room temperature and the reaction mixture was filtered. The collected solid was washed with methanol and subsequently dried under vacuum to afford 2-amino-5-bromopyridine-3-carbaldehyde as a brown solid in 79% yield (12.9 g).
1H NMR (400 MHz, CDCl3): δ 9.81 (s, 1H), 8.30 (d, J = 2.4 Hz, 1H), 7.89 (d, J = 2.4 Hz, 1H), 6.78 (br s, 2H).
References
[1] Patent: WO2015/81257, 2015, A2. Location in patent: Page/Page column 61-62
[2] Journal of Polymer Science, Part A: Polymer Chemistry, 2011, vol. 49, # 19, p. 4204 - 4212
[3] Journal of Medicinal Chemistry, 2014, vol. 57, # 21, p. 8777 - 8791
[4] Patent: WO2013/82756, 2013, A1. Location in patent: Page/Page column 21; 30-31
[5] Patent: WO2009/115788, 2009, A1. Location in patent: Page/Page column 54
