Synthesis
The general procedure for the synthesis of 4-formamidopyridine hydrochloride from 4-cyanopyridine was as follows: 4-cyanopyridine (20.0 g, 0.2 mol) was dissolved in anhydrous methanol (200 mL), followed by a one-time addition of powdered sodium methanol (1.1 g, 20 mmol). The reaction mixture was stirred at room temperature overnight. Next, ammonium chloride (16.5 g, 0.31 mol) was added and the reaction mixture was heated to reflux for 4 hours, after which it was cooled to room temperature. The solvent was removed by evaporation, anhydrous ethanol (300 mL) was added, and the mixture was subsequently heated to reflux. after 15 min, the solid insoluble material was removed by filtration, and the filtrate was cooled to room temperature and allowed to stand overnight. The filtrate was filtered again to remove additional inorganic salts and finally the reaction mixture was concentrated to about one-third of the original volume, which was filtered to give 24.0 g of 4-formamidinopyridine hydrochloride in 76% yield.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 15, p. 3487 - 3490
[2] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 11, p. 3347 - 3356
[3] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 12, p. 2990 - 2993
[4] Journal of Medicinal Chemistry, 1990, vol. 33, # 4, p. 1230 - 1241
[5] Patent: US5294612, 1994, A
