Synthesis
General procedure for the synthesis of 4-amino-5-methyl-3-nitropyridine from 3-methyl-4-aminopyridine: 4-amino-3-methylpyridine (3.00 g) was dissolved in ice-cold concentrated sulfuric acid (36 mL). Subsequently, fuming nitric acid (4.72 g) was added slowly and dropwise. The reaction mixture was stirred at room temperature for 1 hour, then warmed to 60°C and heated continuously for 14 hours. Upon completion of the reaction, it was cooled to ambient temperature, the reaction mixture was slowly poured into ice water and the pH of the solution was adjusted to 13 with solid KOH. The precipitate was collected by filtration, washed with water and dried to afford the target product 4-amino-3-methyl-5-nitropyridine in a yield of 1.198 g (31.3% yield).
References
[1] Patent: WO2005/63744, 2005, A2. Location in patent: Page/Page column 232
[2] Nucleosides, Nucleotides and Nucleic Acids, 2002, vol. 21, # 11-12, p. 737 - 751
