Acetic anhydride (6.209 g, 60.87 mmol) was added slowly and dropwise to a solution of 4-bromo-2-iodo-6-methylaniline (6.31 g, 20.29 mmol) and potassium acetate (2.386 g, 24.35 mmol) in chloroform (100 mL) at 0 °C and under nitrogen protection. The reaction mixture was stirred at room temperature for 1 hour. Subsequently, the reaction system was warmed to 60 °C, tert-butyl nitrite (10.3 g, 0.1 mol) was added and stirred at 60 °C overnight. Upon completion of the reaction, the mixture was diluted with water and extracted with dichloromethane (2 x 100 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was dissolved in a mixture of methanol and 6N hydrochloric acid (1:1, v/v) and stirred at room temperature for 5 hours. The reaction solution was adjusted to alkaline with 10N aqueous sodium hydroxide and extracted again with dichloromethane (2 x 100 mL). The organic layers were combined, washed with saturated saline, dried over anhydrous sodium sulfate and concentrated under reduced pressure. Finally, the residue was purified by silica gel column chromatography with petroleum ether/ethyl acetate (100:10:1) as eluent to afford 5-bromo-7-iodo-1hydro-indazole (3.73 g, 57.1% yield) as a light yellow solid. lc/ivis (ESI) m/z: 323 (M+H)+.
