Uses
6-Methoxy-1H-indazole is used as a raw material for organic synthesis or as a pharmaceutical intermediate compound. It can be used to prepare other heterocyclic compounds such as 1H-Indazol-6-ol, 6-Methoxy-1H-indazol-5-amine and 6-Methoxy-5-nitro-1H-indazole.
Synthesis
The general procedure for the synthesis of 6-methoxy-1H-indazole from 2-fluoro-4-methoxybenzaldehyde is as follows:
Preparation of intermediate 42: 2-fluoro-4-methoxybenzaldehyde (1 g, 6.5 mmol) was mixed with hydrazine (7 mL) and heated to reflux for 4 hours. After completion of the reaction, the reaction mixture was extracted with dichloromethane (3 x 75 mL). The organic layers were combined, washed sequentially with water and saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting crude product was purified by column chromatography (eluent: petroleum ether/ethyl acetate=5:1) to afford 6-methoxy-1H-indazole (Intermediate 42) (568 mg, 59% yield) as a yellow solid.
Product characterization: HPLC purity 99%, retention time 2.159 min; mass spectrum (ESI) m/z 149.1 [M+H]+.
References
[1] Journal of Organic Chemistry, 2006, vol. 71, # 21, p. 8166 - 8172
[2] Journal of Medicinal Chemistry, 2011, vol. 54, # 8, p. 3076 - 3080
[3] Journal of Organic Chemistry, 2009, vol. 74, # 16, p. 6331 - 6334
[4] Patent: WO2012/3418, 2012, A2. Location in patent: Page/Page column 73
[5] Patent: CN108727267, 2018, A. Location in patent: Paragraph 0106; 0107; 0108
