Synthesis
General Method B: The synthesis of pyridine-3-carboxamidine hydrochloride from 3-cyanopyridine was carried out as follows:
1. 3-Cyanopyridine (20 g, 0.2 mol) was dissolved in methanol (200 mL).
2. Powdered sodium methanolate (1.1 g, 20 mmol) was added in a single addition.
3. The reaction mixture was stirred at room temperature overnight.
4. After addition of ammonium chloride (16.5 g, 0.31 mol), the mixture was heated to reflux for 4 hours and then cooled.
5. The solvent was removed under vacuum.
6. Anhydrous ethanol (300 mL) was added and the mixture was heated to reflux and maintained for 15 minutes.
7. After filtering out the solids, the mixture was cooled to room temperature and allowed to stand overnight.
8. The inorganic salt was filtered out again and the reaction mixture was concentrated to about a certain volume and filtered to give pyridine-3-carboxamidine hydrochloride (22.4 g, 74% yield).
Product characterization data.
1H NMR (500 MHz, DMSO-d6) δ 9.5 (bs, 4H), 9.02 (dd, 1H, J = 2.5 Hz, J = 0.9 Hz), 8.86 (dd, 1H, J = 4.9 Hz, J = 1.6 Hz), 8.27 (ddd, 1H, J = 8.0 Hz, J = 2.5 Hz, J = 1.6 Hz), 7.64 (ddd, 1H, J = 8.0 Hz, J = 4.9 Hz, J = 0.9 Hz).
13C NMR (125 MHz, DMSO-d6) δ 164.4, 154.2, 148.9, 136.5, 124.7, 123.9.
HRMS: calculated C6H7N3, 121.0640; measured, 121.0644.
References
[1] Patent: WO2014/128213, 2014, A1. Location in patent: Page/Page column 29
[2] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 15, p. 3487 - 3490
[3] Journal of Medicinal Chemistry, 1990, vol. 33, # 4, p. 1230 - 1241
[4] Patent: US5294612, 1994, A
[5] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 1, p. 299 - 301
