Synthesis
The general procedure for the synthesis of N-(2-hydroxyethyl)-3-pyridinecarboxamide from nicotinic acid and 2-aminoethanol was as follows: suspension of nicotinic acid (0.385 g, 3.13 mmol) in anhydrous toluene (15 mL), addition of thionyl chloride (455 μL, 6.26 mmol), and refluxing of the reaction mixture for 4 hours at 140 °C. After cooling, a clarified solution was obtained and the solvent was removed in vacuum. The solid residue was washed three times with ether, followed by the addition of fresh anhydrous toluene (15 mL) and ethanolamine (756 μL, 12.52 mmol). The mixture was stirred at 50 °C overnight. Upon completion of the reaction, the solvent was removed under vacuum and the solid residue was purified by silica gel column chromatography using dichloromethane/methanol (9.2:0.8) as eluent. The final white solid product N-(2-hydroxyethyl)-3-pyridinecarboxamide (450 mg, 86% yield) was obtained with a melting point of 205 °C. The 1H NMR (300 MHz, DMSO-d6) data of the product were as follows: δ 9.00 (s, 1H, NH), 8.68 (m, 2H, Ar-H), 8.17 (d, 1H, Ar-H), 7.60 (m, 1H, Ar-H), 4.74 (m, 1H, OH), 3.51 (m, 2H, CH2), 3.36 (m, 2H CH2).
References
[1] Patent: WO2006/92204, 2006, A1. Location in patent: Page/Page column 16-17
[2] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 21, p. 5134 - 5147
[3] Archiv der Pharmazie, 2003, vol. 336, # 10, p. 445 - 455
