4.2.1 Synthesis of methyl 4-bromo-1H-indazole-6-carboxylate (13)
Under stirring, amine 12 (4.50 g, 18.4 mmol) was dissolved in acetic acid (80 mL), followed by the slow addition of a solution of sodium nitrite (1.39 g, 20.3 mmol) in water (8 mL). The reaction mixture was stirred at room temperature overnight. Upon completion of the reaction, the solvent was removed by concentration under reduced pressure. The residue was diluted with saturated sodium bicarbonate solution (100 mL) and extracted with ethyl acetate (3 x 30 mL). The organic phases were combined and subjected to standard post-treatment (including washing, drying and concentration). The crude product was initially purified by recrystallization from toluene, and the mother liquor was further purified by fast chromatography (15% ethyl acetate/hexane) to afford the target compound 13 (3.38 g, 72%) as a light orange solid.
Physicochemical properties:
- Rf value (15% ethyl acetate/hexane): 0.25
- Melting point: 173-174°C
- 1H NMR (DMSO-d6, δ): 13.83 (1H, broad single peak), 8.16 (2H, single peak), 7.78 (1H, double peak, J=1.0Hz), 3.90 (3H, single peak)
- 13C NMR (DMSO-d6, δ): 165.3, 139.7, 133.4, 128.4, 125.9, 122.6, 113.2, 111.9, 52.5
- Mass spectra (ESI): m/z 254.9 (M [79Br]H+), 256.9 (M [81Br]H+)
- High-resolution mass spectrum (ESI): calculated value of [M [79Br]H+] for C9H8BrN2O2 is 254.9769, measured value is 254.9765.
