Synthesis
General procedure for the synthesis of 5-nitro-2-(4-methyl-1-piperazinyl)pyridine from N-methylpiperazine and 2-chloro-5-nitropyridine: 2-chloro-5-nitropyridine (3.16 g, 20.0 mmol), N-methylpiperazine (2.00 g, 20.0 mmol) and potassium carbonate (2.76 g, 20.0 mmol) were reacted in a N,N- Dimethylformamide (DMF) in a stirred mixture was heated to 100 °C and reacted for 24 hours. After completion of the reaction, the mixture was cooled to room temperature, poured into water and extracted with dichloromethane (CH2Cl2). The organic phases were combined, dried with anhydrous magnesium sulfate (MgSO4) and concentrated under reduced pressure. The obtained residue was purified by fast column chromatography (silica gel as stationary phase, eluent was a 10:90 ethanol:ethyl acetate mixture containing 2% ammonia) to afford 5-nitro-2-(4-methyl-1-piperazinyl)pyridine as an off-white solid in the yield of 4.0 g (90% yield), and the structure of the product was confirmed by nuclear magnetic resonance (NMR) analysis.
References
[1] Molecules, 2012, vol. 17, # 4, p. 4703 - 4716
[2] Patent: US2004/167030, 2004, A1. Location in patent: Page 9
[3] Patent: US2015/266825, 2015, A1. Location in patent: Paragraph 1279; 1280
[4] European Journal of Medicinal Chemistry, 2018, vol. 158, p. 322 - 333
[5] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 5, p. 1362 - 1365
