1H-Pyrazolo[3,4-b]pyridine

Chemical Properties

Pale Orange Solid

Uses

A pyrazole derivative as kinase inhibitors.

Synthesis Reference(s)

Journal of Heterocyclic Chemistry, 7, p. 247, 1970 DOI: 10.1002/jhet.5570070146

Synthesis

General procedure for the synthesis of 1H-pyrazolo[3,4-b]pyridine from 2-chloro-3-pyridinecarboxaldehyde: Hydrazine hydrate (10 mL) was added to a mixture of 2-chloro-3-formylpyridine (5.00 g, 35 mmol) and p-toluenesulfonic acid (3.50 g, 18 mmol). The reaction mixture was stirred at 130 °C for 3 hours. Upon completion of the reaction, the mixture was cooled with cold water and subsequently extracted with ethyl acetate. The organic phases were combined and dried with anhydrous magnesium sulfate. After filtration, the solvent was removed by distillation under reduced pressure to afford the target compound 1H-pyrazolo[3,4-b]pyridine (3.65 g, 87% yield) as a yellow solid. The melting point of the compound was 88-90 °C (literature value 97-98 °C). Its Fourier transform infrared spectrum (KBr) showed characteristic absorption peaks: νmax/cm-1 3450 (NH), 3089, 3026 (aromatic CH), 2958, 2915 (CH), 1606, 1588, 1509, 1470, 1429 (C=N, C=C). The NMR hydrogen spectrum (300 MHz, CDCl3) data are as follows: δ/ppm 1.69 (s, 1H, NH), 7.19 (dd, 1H, J=4.7 and 7.5 Hz, ArH, 5-H), 8.12 (s, 1H, ArH, 3-H), 8.15 (d, 1H, J=8.1 Hz, ArH, 4-H), 8.63 (d, 1H, J=4.5Hz, ArH, 6-H).

References

[1] European Journal of Medicinal Chemistry, 2012, vol. 57, p. 311 - 322
[2] Journal of Organic Chemistry, 2017, vol. 82, # 23, p. 12300 - 12306
[3] Journal of the Brazilian Chemical Society, 2013, vol. 24, # 8, p. 1295 - 1306
[4] Patent: EP1921078, 2008, A1. Location in patent: Page/Page column 32
[5] Patent: US2007/21442, 2007, A1. Location in patent: Page/Page column 56