5-broMo-7-(trifluoroMethyl)-1H-indazole

To a mixture of 133-S2(700 mg, 2.77 mmol) and potassium acetate (325.8 mg, 3.32 mmol) in CHC13 (20 mL) was addeddropwise acetic anhydride (846.6 mg, 8.30 mmol) at 0 °C. The resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was heated to 60 °C and tert-butyl nitrite (570.6 mg, 5.54 mmol) was added. After stirring overnight at 60 °C, the mixture was diluted with water and extracted with DCM twice. The combined organic layers were washed with brine, dried overanhydrous Na2SO4, and concentrated under reduced pressure. The remaining residue was dissolved in MeOH (5 mL) and 6 N HC1 (5 mL). The mixture was stirred at room temperature for 4 hours, basified with 10 N aqueous NaOH solution, and extracted with DCM twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The remaining residue was purified by column chromatography on silica gel (PE/EtOAc= 10:1 to 3:1) to afford 133-S3 (420 mg, 57.5percent yield) as a yellow oil. LC/MS (ESI) m/z: 265 (M+H).To a solution of 4-bromo-2-methyl-6-(trifluoromethyl)aniline (3.3 g, 13 mmol) in toluene (65 mL) and glacial acetic acid (11.2 mL, 195 mmol) was added potassium acetate (10.2 g, 104 mmol) portionwise. After 15 minutes a large amount of precipitate had formed, hindering stirring of the reaction. The reaction was diluted with acetic acid (10 mL). Isoamyl nitrite (1.92 mL, 14.3 mmol) was then added dropwise and the reaction was stirred at room temperature for 3 hours. Additional isoamyl nitrite (0.5 mL, 3.7 mmol) was added and the reaction was left stirring for 15 hours. The reaction was diluted with water (100 mL) and stirred for 1.5 hours. The solution was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The layers were separated and the organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (5-50percent ethyl acetate/heptanes) gave the title compound (1.78 g, 52percent) as a yellow powder. -ESI (M-H+1) 264.9; To a mixture of 133-S2(700 mg, 2.77 mmol) and potassium acetate (325.8 mg, 3.32 mmol) in CHC13 (20 mL) was addeddropwise acetic anhydride (846.6 mg, 8.30 mmol) at 0 °C. The resulting mixture was stirred at room temperature for 1 hour. The reaction mixture was heated to 60 °C and tert-butyl nitrite (570.6 mg, 5.54 mmol) was added. After stirring overnight at 60 °C, the mixture was diluted with water and extracted with DCM twice. The combined organic layers were washed with brine, dried overanhydrous Na2SO4, and concentrated under reduced pressure. The remaining residue was dissolved in MeOH (5 mL) and 6 N HC1 (5 mL). The mixture was stirred at room temperature for 4 hours, basified with 10 N aqueous NaOH solution, and extracted with DCM twice. The combined organic layers were washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The remaining residue was purified by column chromatography on silica gel (PE/EtOAc= 10:1 to 3:1) to afford 133-S3 (420 mg, 57.5percent yield) as a yellow oil. LC/MS (ESI) m/z: 265 (M+H).To a solution of 4-bromo-2-methyl-6-(trifluoromethyl)aniline (3.3 g, 13 mmol) in toluene (65 mL) and glacial acetic acid (11.2 mL, 195 mmol) was added potassium acetate (10.2 g, 104 mmol) portionwise. After 15 minutes a large amount of precipitate had formed, hindering stirring of the reaction. The reaction was diluted with acetic acid (10 mL). Isoamyl nitrite (1.92 mL, 14.3 mmol) was then added dropwise and the reaction was stirred at room temperature for 3 hours. Additional isoamyl nitrite (0.5 mL, 3.7 mmol) was added and the reaction was left stirring for 15 hours. The reaction was diluted with water (100 mL) and stirred for 1.5 hours. The solution was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The layers were separated and the organics were washed with brine, dried over magnesium sulfate, filtered, and concentrated. Purification by flash column chromatography (5-50percent ethyl acetate/heptanes) gave the title compound (1.78 g, 52percent) as a yellow powder. -ESI (M-H+1) 264.9; 5-Bromo-7-(trifluoromethyl)-1H-indazole 1a (0.5 g, 1.88 mmol, was added sequentially under an argon atmosphere.Prepared by the method disclosed in the patent application 'WO2012056372'), 4, 4, 4, 4, 5, 5, 5, 5-octamethyl-2, 2-bis(1, 3, 2-dioxaborolane) 1b (575 mg, 2.26 mmol) ), [1, 1'-bis(diphenylphosphino)ferrocene]palladium dichloride (275 mg, 0.38 mmol) and potassium acetate (554 mg, 5.66 mmol) were dissolved in 10 mL of ethylene glycol dimethyl ether solution.Heat to 80 C and stir for 2 hours. Stop the reaction and cool to room temperature.Filtration, the filtrate was distilled under reduced pressure, and the residue was purified using a CombiFlash rapid preparation apparatus using eluent system C.The title compound 1c (270 mg, yield: 45.9%) was obtained.5-Bromo-7-(trifluoromethyl)-1H-indazole 9a (0.5 g, 1.88 mmol, prepared according to the method disclosed in the patent application "), compound 5a (575 mg, 2.26 mmol), [1, 1'-bis(diphenylphosphino)ferrocene]dichloropalladium (275 mg, 0.38 mmol) and potassium acetate (554 mg, 5.66 mmol) were dissolved successively in 10 mL of glycol dimethyl ether under an argon atmosphere. The reaction solution was heated to 80C, and stirred for 2 hours. The reaction was stopped, and the reaction solution was cooled to room temperature and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by CombiFlash rapid preparation instrument with eluent system C to obtain the title compound 9b (270 mg, yield: 45.9%).

Molecular Weight:265.03
XLogP3:3.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:4
Exact Mass:263.95100
Monoisotopic Mass:263.95100
Topological Polar Surface Area:28.7
Heavy Atom Count:14
Complexity:221
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes