1H-Indazole,7-broMo-5-(trifluoroMethyl)-

1100212-65-4

1100212-66-5

General procedure for the synthesis of 7-bromo-5-(trifluoromethyl)-1H-indazole from 2-bromo-6-methyl-4-(trifluoromethyl)aniline: to a suspension of 2-bromo-6-methyl-4-(trifluoromethyl)aniline (11.3 g, 44.5 mmol) in hydrochloric acid (8 M, 40 mL, 320 mmol) was added slowly and dropwise at -10 °C sodium nitrite (3.22 g) , 46.7 mmol) in aqueous solution (~10 mL). After 10 min of reaction, solid sodium acetate was added to neutralize the reaction solution. The neutralized solution was slowly added to a solution of 2-methyl-2-propanethiol (5.01 mL, 44.5 mmol) in ethanol (100 mL) at 0 °C. The reaction mixture was continued to be stirred at 0 °C for 30 min. Subsequently, the reaction mixture was poured on ice and extracted with ether (2×). The combined organic phases were washed sequentially with water and brine, dried over magnesium sulfate and concentrated. The concentrated residue was dissolved in dimethyl sulfoxide (25 mL) and transferred to a solution of potassium tert-butoxide (39.9 g, 356 mmol) in dimethyl sulfoxide (250 mL) through a cannula in a cold water bath (about 10 °C). After removal of the cold water bath, stirring was continued for 30 min. The reaction mixture was poured into ice/concentrated hydrochloric acid and a precipitate was precipitated. after 30 min, the solid was collected by filtration and air-dried on a filter overnight to give 10.1 g of brown solid product in 86% yield. The product was confirmed by 1H-NMR (CDCl3,500MHz) and 13C-NMR (CDCl3,126MHz) characterization.