Synthesis
The general procedure for the synthesis of 7-bromo-5-chloro-1H-indazole from 4-chloro-2-methylaniline was as follows: 2-bromo-4-chloro-6-methylaniline (13.2 g, 59.90 mmol) was suspended in 24% hydrochloric acid (40 mL). The stirred mixture was cooled to 0°C and a solution of sodium nitrite (4.54 g, 65.90 mmol) in water (10 mL) was added slowly and dropwise over 30 minutes. Subsequently, the mixture was warmed to about 50°C and the pH was adjusted with sodium acetate to 5. The mixture was maintained at 0°C and a solution of 2-methyl-2-propanethiol (6.8 mL, 59.9 mmol) in ethanol (40 mL) was added in batches over 30 minutes. After addition, stirring was continued at 0°C for 30 min, then the reaction mixture was poured into crushed ice and extracted with ethyl acetate (2×). The organic phases were combined, washed with brine (2×), dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was dissolved in dimethyl sulfoxide (50 mL) and transferred to a solution of potassium tert-butoxide (53.7 g, 479 mmol) in dimethyl sulfoxide (200 mL) via cannula at 0°C. The residue was extracted with ethyl acetate (2×). The ice bath was removed and stirring was continued for 30 min. Subsequently, the reaction mixture was poured into a mixture of crushed ice (400 mL) and 10% hydrochloric acid (200 mL), a precipitate was precipitated and collected by filtration. The resulting solid was ground with hexane to give 7.5 g (54% yield) of brown powdery product.1H-NMR (CDCl3, 300 MHz) δ 7.97 (s, 1H), 7.60 (s, 1H), 7.44 (s, 1H). MS: 232.90 (MH)+.
