The general procedure for the synthesis of 6-bromo-5-methyl-1H-indazole from 5-bromo-2,4-dimethylaniline was as follows: to a solution of 5-bromo-2,4-dimethylaniline (15.09 g, 75.0 mmol) in chloroform (150 mL) was added sequentially, under ice-bath conditions, acetic anhydride (Ac2O, 15.0 g, 150 mmol), potassium acetate (KOAc. 8.009 g, 82.5 mmol), 18-crown-6 (10.0 g, 37.5 mmol) and isoamyl nitrite (26.3 g, 225 mmol). The reaction mixture was heated to reflux for 36 hours. After completion of the reaction, the reaction mixture was concentrated and the residue was dissolved in ethyl acetate (EtOAc, 500 mL). The organic phase was washed with water (100 mL), dried over anhydrous sodium sulfate (Na2SO4) and concentrated. The residue was dissolved in tetrahydrofuran (THF, 100 mL) and sodium hydroxide solution (4 M, 40.0 mL, 160 mmol) was added. After stirring for 1 h at room temperature, the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate (400 mL) and water (200 mL). The organic layer was washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude product was purified by column chromatography (petroleum ether: ethyl acetate, gradient elution from 10:1 to 5:1) to afford 6-bromo-5-methyl-1H-indazole (5.1 g, 32% yield) as an orange solid.1H NMR (300 MHz, CDCl3): δ 10.20 (brs, 1H), 7.99 (s, 1H), 7.75 (s, 1H) 7.61 (s, 1H), 2.50 (s, 3H).
