The general procedure for the synthesis of 4-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole from 3,4-dihydro-2H-pyran and 4-bromo-1H-indazole was as follows: 3,4-dihydro-2H-pyran (5.36 mL, 58.57 mmol) was added to a solution of 3,4-dihydro-2H-pyran (5.36 mL, 58.57 mmol) containing 4-bromo-1H-indazole (5.77 g, 29.3 mmol) and 4-bromo-1H-sulphonic acid ( 0.176 g, 1.02 mmol) in a solution of ethyl acetate (60 mL). The reaction mixture was heated and stirred at 70 °C for 16 hours. After the reaction was completed, the mixture was cooled to room temperature and neutralized by adding saturated aqueous sodium bicarbonate solution (50 mL). The organic and aqueous phases were separated and the aqueous phase was extracted with ethyl acetate (10 mL). The organic layers were combined and washed sequentially with saturated aqueous sodium bicarbonate (10 mL) and saturated aqueous sodium chloride (10 mL). The organic layer was dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The resulting brown oil was purified by fast silica gel column chromatography with the eluent being a heptane solution of 10% ethyl acetate. The product fraction was collected and the solvent was evaporated under reduced pressure to give 4-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (7.78 g, 94% yield) as a white solid. The product was confirmed by 1H NMR (400 MHz, CDCl3, 30 °C): δ 1.60-1.88 (3H, m), 2.03-2.23 (2H, m), 2.55 (1H, dddd), 3.73 (1H, dddd), 4.00 (1H, dddd), 5.71 (1H, dddd), 7.19-7.24 (1H, m), and 7.32 (1H, dd), 7.55 (1H, dd), 8.03 (1H, d).
