General procedure for the synthesis of 2-(benzylamino)nicotinic acid from 2-chloronicotinic acid and benzylamine: benzylamine (14 mL, 126.8 mmol) was slowly added to a pyridine solution of 2-chloronicotinic acid (10 g, 63.4 mmol), followed by heating and refluxing the reaction overnight. Upon completion of the reaction, the pyridine solvent was removed by distillation. The residue was dissolved in 1 N aqueous sodium hydroxide solution, diluted with water until the pH was adjusted to 10-11, and washed with dichloromethane to remove organic impurities. The aqueous phase was neutralized with cold 10% aqueous hydrochloric acid to pH 6-7, at which point the target product 2-(benzylamino)nicotinic acid precipitated as a solid. The solid was collected by filtration, washed with cold water and dried in a vacuum oven to give 12.2 g of white solid product in 84% yield. The product was characterized as follows: melting point 148 °C; 1H-NMR (DMSO-d6) δ: 4.69 (d, J = 3.6 Hz, 2H), 6.61 (dd, J = 4.9, 7.7 Hz, 1H), 7.23 (m, 1H), 7.29 (m, 4H), 8.08 (dd, J = 1.8, 7.0 Hz, 1H), 8.28 (dd, J = 1.8, 7.0 Hz, 1H), 8.28 (dd, J = 1.8, 7.0 Hz, 1H). J = 1.8, 7.0 Hz, 1H), 8.47 (br.s, 1H), 13.10 (s, 1H); EIMS: 229 (M + 1), 251 (M + 23).
