Synthesis
General procedure for the synthesis of methyl 1H-benzo[d]imidazole-4-carboxylate from methanol and benzimidazole-7-carboxylic acid: benzimidazole-7-carboxylic acid (1.136 g, 7.02 mmol) was dissolved in methanol (115 mL) and concentrated HCl and H2SO4 (0.86 mL, 15.45 mmol) were added. The reaction mixture was heated under reflux conditions until thin layer chromatography (TLC) showed that the reaction was complete (24-36 hours). Upon completion of the reaction, the mixture was concentrated to a few mL and the pH was adjusted to 8.5 with 1 M K3PO4 solution. the resulting precipitate was separated by filtration and dried under reduced pressure to afford methyl 1H-benzo[d]imidazole-4-carboxylate (0.940 g, 76% yield) as a white solid. The melting point was 211-213 °C (literature value 204 °C).1H NMR (300 MHz, DMSO-d6) δ 8.31 (s, 1H), 7.95 (dd, J = 8.0,0.9 Hz, 1H), 7.83 (dd, J = 7.6,0.9 Hz, 1H), 7.29 (dd, J = 8.0,7.6 Hz, 1H).13C NMR (75 MHz, DMSO-d6) δ 265.5,144.1,143.6,132.3,124.7,124.3,121.0,113.8.
References
[1] Australian Journal of Chemistry, 1993, vol. 46, # 8, p. 1177 - 1191
[2] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 14, p. 3933 - 3937
[3] Patent: WO2016/138335, 2016, A1. Location in patent: Paragraph 00366
