Uses
7-Bromo-1H-indazole serves as a starting material for the synthesis of 1H-indazole-7-carboxylic acid via lithiation followed by carbon dioxide addition[4]. The compound acts as an inhibitor of human serum paraoxonase 1 (hPON1) activity in vitro, with molecular docking studies assessing its binding mechanisms within the enzyme's active site[5].
Synthesis
The general procedure for the synthesis of 7-bromo-1H-indazole from 7-aminoindazole was as follows: 7-aminoindazole (3.45 g, 25.9 mmol) was dissolved in concentrated hydrobromic acid (25 mL), diluted with water (8.5 mL), and cooled to -10 °C. In another vessel, sodium nitrite (755 mg, 10.9 mmol) was dissolved in water (11.5 mL), cooled and slowly added to the above solution. Subsequently, solid sodium nitrite (1.14 g, 16.5 mmol) was added in batches. The reaction solution was stirred at -5°C for 15 minutes, and then a concentrated hydrobromic acid (11.5 mL) solution of cooled cuprous bromide (3.94 g, 27.5 mmol) was added dropwise over 15 minutes. The reaction mixture was stirred at room temperature for 2 hours and then neutralized with saturated sodium bicarbonate solution. The neutralized mixture was diluted with water (50 mL), filtered and the filter cake was washed with ethyl acetate (300 mL). The filtrate layer was separated and the aqueous layer was extracted with ethyl acetate (3 x 200 mL). The organic layers were combined, dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 7-bromo-1H-indazole (1.88 g, 37% yield).
References
[1] Patent: US2006/270686, 2006, A1. Location in patent: Page/Page column 25-26
[2] Patent: US2008/280891, 2008, A1. Location in patent: Page/Page column 26
[3] Patent: WO2008/8059, 2008, A1. Location in patent: Page/Page column 65-66
[4]
Cottyn, B., Acher, F., Ramassamy, B., Alvey, L., Lepoivre, M., Frapart, Y., Stuehr, D., Mansuy, D., Boucher, J.-L., & Vichard, D. (2008). Inhibitory effects of a series of 7-substituted-indazoles toward nitric oxide synthases: Particular potency of 1H-indazole-7-carbonitrile. Bioorganic & Medicinal Chemistry, 16(11), 5962–5973.
https://doi.org/10.1016/j.bmc.2008.04.056[5]
Alım, Z., Kılıç, D., & Demir, Y. (2018). Some indazoles reduced the activity of human serum paraoxonase 1, an antioxidant enzyme:
in vitro inhibition and molecular modeling studies. Archives of Physiology and Biochemistry, 125(5), 387–395.
https://doi.org/10.1080/13813455.2018.1470646
