1031417-71-6

70598-49-1

635712-49-1

1031417-71-6

N-Bromosuccinimide (NBS, 2.66 g, 14.9 mmol) was slowly added to a solution of N,N-dimethylformamide (DMF, 50 mL) of 2-ethyl-6-methylaniline (2.03 g, 15 mmol) at 0 °C. The reaction mixture was stirred at room temperature for 10 min and then poured into saturated aqueous sodium chloride solution to terminate the reaction. The mixture was extracted with ethyl acetate (EtOAc) and the organic phase was washed twice with saturated aqueous sodium chloride solution, concentrated and purified by a Biotage fast chromatography system (40M silica gel column, 15% ethyl acetate/heptane as eluent) to give 4-bromo-2-ethyl-6-methylaniline as a reddish-brown liquid (3.21 g, 100% yield). 4-Bromo-2-ethyl-6-methylaniline (3.21 g, 15 mmol) was dissolved in acetic acid (50 mL) and stirred for 3 h. After stirring, 2 M aqueous sodium nitrite (11 mL, 22.5 mmol) was slowly added. The reaction mixture was stirred at room temperature overnight. The reaction solution was concentrated and the residue was dissolved in ethyl acetate and washed three times with saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by a Biotage fast chromatography system (40M silica gel column, 15-30% ethyl acetate/heptane gradient elution) to afford 5-bromo-7-ethyl-1H-indazole (1.11 g, 33% yield) and 5-bromo-3,7-dimethyl-1H-indazole (0.84 g, 25% yield), respectively. 5-Bromo-7-ethyl-1H-indazole (225 mg, 1.00 mmol) was dissolved in 1,4-dioxane (1.5 mL) and sequentially added molybdenum hexacarbonyl (132 mg, 0.50 mmol), Herrmann's catalyst (trans-bis(acetic acid)bis[o-(di-o-tolylphosphino)benzyl]dipalladium, 46.9 mg, 0.05 mmol ) and aqueous sodium carbonate (318 mg, 3.00 mmol, dissolved in 2 mL of water). The reaction suspension was sealed and placed in a microwave reactor and irradiated at 165 °C for 15 min (high absorption setting). After completion of the reaction, the reaction vial was opened, filtered through diatomaceous earth, the filter cake was washed with ethyl acetate and the filtrate was concentrated to give the target compound (140 mg, 74% yield).