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

Synthesis

The general procedure for the synthesis of ethyl 4-azaindole-2-carboxylate (4a-1) from the compound (CAS: 23596-34-1) was as follows: ethyl 1H-pyrrolo[3,2-b]pyridine-2-carboxylate (56.8 g, 0.24 mol), ethanol (850 mL), and 10% Pd/C (5.7 g, 10 wt%) were added to a 2 L thick-walled Parr reactor. The reactor was connected to the Parr hydrogenation unit and after flushing with hydrogen, the orange slurry was pressurized to 45 psi. the reaction temperature was raised to 57 °C by shaking for 1 h at room temperature. After the temperature of the reaction mixture stabilized at 35°C, it was slowly heated to 40°C and maintained for 3 hr. After confirming the completion of the reaction by TLC (silica gel plate, unfolding agent was CH2Cl2 solution with 1% MeOH), the reaction mixture was cooled to room temperature, the slurry was filtered through Celite and the filter cake was washed with ethanol (4 x 200 mL). The yellow filtrate was concentrated to obtain a solid (41.6 g), to which ethyl acetate (302 mL) was added and heated on a steam bath. After cooling the mixture to room temperature, heptane (600 mL) was added to precipitate the product. The mixture was stirred in an ice bath for 1 hour and then filtered and the filter cake was washed with heptane (100 mL). The filter cake was dried at 50 °C, 0.1 mmHg for 24 h to give light gray solid 4a-1 (36.6 g, 81% yield).1H NMR (DMSO-d6) δ 1.36 (t, 3H, J=7.0 Hz), 4.36 (q, 2H, J=7.0 Hz), 7.19 (s, 1H), 7.25 (dd, 1H, J=4.5, 8.1 Hz), 7.82 (d, 1H, J=8.1 Hz), 8.44 (d, 1H, J=4.5 Hz), 12.11 (s, 1H).

References

[1] Organic Process Research and Development, 2011, vol. 15, # 5, p. 1040 - 1045
[2] Patent: US2005/131012, 2005, A1. Location in patent: Page/Page column 14
[3] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 339 - 342