1H-Pyrazolo[3,4-b]pyridine, 3-bromo-5-nitro-

Synthesis

The general procedure for the synthesis of 3-bromo-5-nitro-1H-pyrazolo[3,4-b]pyridine from 5-nitro-7-azaindazole was as follows: a 4N NaOH solution (5.12 mL, 20.5 mmol) was slowly added to a dioxane (30 mL) solution of 5-nitro-1H-pyrazolo[3,4-b]pyridine (0.84 g, 5.12 mmol) at 0 °C. ) solution, followed by dropwise addition of bromine (1.05 mL, 20.5 mmol). After removal of the ice bath, the reaction mixture was stirred at room temperature for 30 min. Upon completion of the reaction, the reaction mixture was diluted with ethyl acetate (100 mL) and the reaction was quenched with saturated aqueous Na2S2O3 solution (50 mL). The aqueous layer was further extracted with ethyl acetate (100 mL). The organic layers were combined, dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using hexane/ethyl acetate (9:1, v/v) as eluent to afford 3-bromo-5-nitro-1H-pyrazolo[3,4-b]pyridine (1.10 g, 88% yield) as solid.

References

[1] Patent: WO2011/25968, 2011, A1. Location in patent: Page/Page column 49
[2] Patent: WO2009/111279, 2009, A1. Location in patent: Page/Page column 96
[3] ACS Medicinal Chemistry Letters, 2011, vol. 2, # 5, p. 342 - 347