Synthesis
General procedure for the synthesis of 3-amino-6-fluoro-1H-indazole from 2,4-difluorobenzonitrile: 2,4-difluorobenzonitrile (10.00 g, 71.89 mmol) was placed in a 500 mL two-necked round-bottomed flask and n-butanol (200 mL) was added as a solvent. Hydrazine hydrate (70.0 mL, 1443 mmol) was slowly added to the reaction system under nitrogen protection. After addition, the reaction mixture was heated to 150 °C and stirred continuously for 17 hours. After completion of the reaction, the mixture was cooled to room temperature and extracted with ethyl acetate (200 mL x 3). The organic phases were combined, washed sequentially with water (200 mL x 2) and saturated saline (200 mL), dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography with the eluent of petroleum ether/ethyl acetate (v/v=1/2) to afford 3-amino-6-fluoro-1H-indazole as a yellow liquid (4.85 g, 44.7% yield). Mass spectrum (ESI, positive ion mode) m/z: 152.2 ([M+H]+).
References
[1] Patent: WO2018/188590, 2018, A1. Location in patent: Paragraph 00316
[2] Patent: US2009/270405, 2009, A1. Location in patent: Page/Page column 82-83
[3] Patent: WO2011/53292, 2011, A1. Location in patent: Page/Page column 133
[4] Patent: JP5714745, 2015, B2. Location in patent: Paragraph 0264; 0265
