1H-Pyrrolo[2,3-b]pyridine-5-carbonitrile

Chemical Properties

Yellow fine crystalline powder

Uses

5-Cyano-7-azaindole is a commonly used intermediate in the synthesis of new anti-tumor drug protease inhibitors, mainly used in laboratory research and development processes and chemical production processes.

Synthesis

1. 5-Bromo-1H-pyrrolo[2,3-b]pyridine (5.0 g, 25.0 mmol, 1.0 eq.) and zinc cyanide (3.6 g, 20.0 mmol, 0.8 eq.) were dissolved in anhydrous DMF (65 mL) and deoxygenated for 30 min under argon protection. 2. tetrakis(triphenylphosphine)palladium (1.7 g, 1.5 mmol, 0.06 eq.) was added and the reaction mixture was heated at 80 °C for 36 hours. 3. After completion of the reaction, the reaction was quenched with water and extracted with ethyl acetate (EtOAc). 4. The organic layers were combined, dried over anhydrous sodium sulfate (Na2SO4) and concentrated to dryness under reduced pressure. 5. The residue was treated with a small amount of dichloromethane (CH2Cl2) and the precipitate was collected by filtration. 6. The precipitate was washed with dichloromethane and dried over air to give 1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (Intermediate 2a) as a white solid (3.0 g; yield: 83%; UPLC purity: 100%).

References

[1] Patent: US2018/179199, 2018, A1. Location in patent: Paragraph 0451-0452
[2] Patent: WO2004/78756, 2004, A2. Location in patent: Page 120-121
[3] Patent: EP1782811, 2007, A1. Location in patent: Page/Page column 63
[4] Patent: WO2014/73904, 2014, A1. Location in patent: Paragraph 1425-1427