Synthesis
General procedure for the synthesis of N-phenylisonicotinamide from isonicotinic acid and aniline: isonicotinic acid (14.5 g, 40.6 mmol) was dissolved in thionyl chloride (40 mL) and heated to reflux for 2 hours. After completion of the reaction, thionyl chloride was removed by distillation under reduced pressure. To the residue was added THF (50 mL), K2CO3 (16.8 g, 121.9 mmol) and aniline (3.78 g, 40.6 mmol), and the reaction mixture was stirred at room temperature for 24 hours. After completion of the reaction, the reaction mixture was diluted with water (100 mL) and extracted with EtOAc (2 x 100 mL). The organic layers were combined, concentrated, and the residue was recrystallized with EtOAc-hexane (60:40) to afford the light yellow solid product N-phenylisonicotinamide (8.0 g, 99% yield) with melting point 166-168 °C. IR (KBr) νmax 1344, 1653, 1465, 665 cm-1 ; 1H NMR (DMSO-d6, 300 MHz) δ 10.49 (s, 1H), 8.78 (m, 2H), 7.86 (m, 2H), 7.78 (m, 2H), 7.39 (t, J = 8.0 Hz, 2H), 7.15 (t, J = 6.5 Hz, 1H).
References
[1] Patent: WO2017/160898, 2017, A1. Location in patent: Paragraph 00105; 00125
[2] Journal of Medicinal Chemistry, 2016, vol. 59, # 4, p. 1370 - 1387
[3] Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 11, p. 6027 - 6033
[4] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1981, vol. 20, # 11, p. 1007 - 1008
