Synthesis
General procedure for the synthesis of methyl 3-carboxylic acid pyridine-2-carboxylate from methanol and 2,3-pyridinedicarboxylic anhydride: 2,3-pyridinedicarboxylic anhydride (5.0 g, 34 mmol) was dissolved in methanol (25 mL). The reaction mixture was heated to reflux for 2 hours and the solvent was subsequently removed by rotary evaporation. The resulting white solid was dissolved in ethyl acetate (25 mL) under reflux conditions and the insoluble by-products were removed by filtration. The filtrate was concentrated under reduced pressure and recrystallized from ethyl acetate to give the final methyl 3-carboxypyridine-2-carboxylate (4.5 g, 71% yield) as a white solid with a melting point of 157-159 °C.1H NMR (300 MHz, CDCl3) δ 8.84 (dd, J=1.7,5.0 Hz, 1H), 8.34 (dd, J=1.6, 7.9 Hz, 1H), 7.57 (dd, J=5.0,8.1 Hz, 1H), 4.00 (s, 3H).
References
[1] Angewandte Chemie - International Edition, 2011, vol. 50, # 22, p. 5192 - 5196
[2] Synlett, 2006, # 12, p. 1938 - 1942
[3] Journal of Medicinal Chemistry, 2016, vol. 59, # 8, p. 3840 - 3853
[4] Patent: WO2017/160898, 2017, A1. Location in patent: Paragraph 00107; 00136
[5] Journal of Medicinal Chemistry, 2006, vol. 49, # 15, p. 4544 - 4567
