1H-Pyrrolo[2,3-b]pyridine-2-carboxylic acid, ethyl ester

Uses

1H-pyrrolo[2,3-B]pyridine-2-carboxylic acid ethyl ester is an important raw material in organic synthesis. Its derivative, pyrrolopyridine-2-carboxamide, is a glycogen phosphorylase inhibitor used to prevent or treat diabetes, hypertension, hypercholesterolemia, hyperinsulinemia, hyperlipidemia, atherosclerosis, or tissue ischemia, and can also be used as a cardioprotective agent.

Synthesis

General procedure for the synthesis of ethyl 1H-pyrrolo[2,3-B]pyridine-2-carboxylate from compound (CAS: 287384-79-6): compound 29 (9.7 g, 31.4 mmol, 1 equiv.) was dissolved in 6 N hydrochloric acid solution (50 mL) and stirred for 2 hr at 50 °C, followed by continued stirring at room temperature overnight. Upon completion of the reaction, the pH of the reaction mixture was adjusted to 13 with solid potassium carbonate (K2CO3), followed by extraction with ethyl acetate (EtOAc). The organic phases were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the target product 30 (6.0 g, 100% yield). The structure of the product was confirmed by 1H NMR (400 MHz, DMSO-d6): δ 11.12 (br s, 1H), 8.59 (d, J = 4.8 Hz, 1H), 8.05 (dd, J = 8.0, 1.6 Hz, 1H), 7.19 (s, 1H), 7.18-7.15 (m, 1H), 4.46 (q, J = 6.8 Hz. 2H), 1.44 (t, J = 6.8 Hz, 3H).

References

[1] European Journal of Medicinal Chemistry, 2014, vol. 88, p. 3 - 9
[2] Patent: WO2015/187428, 2015, A1. Location in patent: Paragraph 00502; 00505; 00506
[3] Patent: US2009/318455, 2009, A1. Location in patent: Page/Page column 69; 93