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5-Bromo-3-hydroxy-2-nitropyridine was used to design potent and selective inhibitors to overcome clinical anaplastic Lymphoma kinase mutations resistant to Crizotinib (C785000), a potential antitumor agent.

Step 1: Synthesis of 5-bromo-2-nitropyridin-3-ol 3-Bromo-5-hydroxypyridine (2 g, 0.011 mol) was dissolved in concentrated sulfuric acid (6 mL), and fuming nitric acid (0.52 mL, 0.011 mol) was slowly added dropwise under the condition of cooling in an ice bath. After the dropwise addition, the reaction mixture was stirred at room temperature for 20 hours. After completion of the reaction, the mixture was carefully poured into ice water and stirred thoroughly. The precipitated solid was collected by filtration and washed with cold water to afford the target product 5-bromo-2-nitropyridin-3-ol (2.2 g, 90% yield) in the form of a light yellow solid.

[1] Patent: US2012/220551, 2012, A1. Location in patent: Page/Page column 20
[2] Organic Process Research and Development, 2017, vol. 21, # 1, p. 133 - 137
[3] Bioorganic and Medicinal Chemistry Letters, 2015, vol. 25, # 17, p. 3636 - 3643