Synthesis
General procedure for the synthesis of 3-methylpyridine-4-carboxamide from 3-methyl-4-pyridinecarboxylic acid: 3-methyl-4-pyridinecarboxylic acid (0.5 g, 3.6 mmol) was dissolved in thionyl chloride (3 mL) and heated to reflux for 3 hours. Upon completion of the reaction, the excess thionyl chloride was removed by evaporation under reduced pressure. The resulting chloride solid was added to ammonium hydroxide solution (30 mL, 25% aqueous solution) in batches under ice bath conditions. Subsequently, the reaction mixture was slowly warmed to room temperature and stirred for 10 minutes. The reaction mixture was concentrated under reduced pressure and the resulting residue was purified by silica gel fast column chromatography (eluent: methanol/dichloromethane, 40:1) to give a white solid product in 63% yield. The product was characterized by 1H NMR (400 MHz, CD3OD): δ 8.50-8.48 (m, 1H), 8.46-8.44 (m, 1H), 7.42 (d, J = 5.0 Hz, 1H), 2.45 (s, 3H).
References
[1] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 12, p. 3559 - 3572
[2] Journal of Medicinal Chemistry, 2012, vol. 55, # 4, p. 1682 - 1697
[3] Patent: US2014/18360, 2014, A1
[4] Chemistry - A European Journal, 2016, vol. 22, # 24, p. 8301 - 8308
