Uses
Indazole-3-carboxylic Acid Methyl Ester has potential as application of N-benzoylindazole derivatives and analogues as inhibitors of human neutrophil elastase. Also used in the preparation of indazole-pyridine based protain kinase/Akt inhibitors.
Definition
ChEBI: 1H-indazole-3-carboxylic acid methyl ester is a member of indazoles.
Synthesis
Indazole-3-carboxylic acid (5.0 g, 30.8 mmol) was dissolved in methanol (50 mL) at 0 °C and thionyl chloride (15 mL) was added slowly and dropwise. After the dropwise addition was completed, the reaction mixture was heated to reflux temperature and maintained at this temperature for 1.5 hours. Upon completion of the reaction, the reaction mixture was concentrated under reduced pressure to give the crude product. The crude product was neutralized by adding saturated sodium bicarbonate solution (50 mL) to the crude product and subsequently extracted with ethyl acetate (50 mL x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure to afford methyl 1H-indazole-3-carboxylate as a white solid (5.1 g, 94% yield). The NMR hydrogen spectrum (300 MHz, d6-DMSO) data were as follows: δ 13.91 (s, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.44 (ddd, J = 8.3 Hz, 6.9 Hz, 1.1 Hz, 1H), 7.30 (dd, J = 7.9 Hz, 6.9 Hz, 0.9 Hz, 1H), 3.92 (s, 3H).
References
[1] Tetrahedron Letters, 2007, vol. 48, # 14, p. 2457 - 2460
[2] Chemical Communications, 2010, vol. 46, # 33, p. 6165 - 6167
[3] ChemMedChem, 2017, vol. 12, # 19, p. 1578 - 1584
[4] Patent: WO2013/120104, 2013, A2. Location in patent: Paragraph 00210; 00211
[5] RSC Advances, 2015, vol. 5, # 100, p. 81817 - 81830
