4-Bromo-1-methyl-3-(trifluoromethyl)-1H-pyrazole

Light yellow liquid or solid

Into a 10-mL sealed tube purged and maintained with an inert atmosphere of argon, was placed a solution of 1-methyl-3-(trifluoromethyl)-1H-pyrazole (10.0 g, 66.62 mmol) and NBS (16.2 g, 66.62 mmol) in DMF (100 mL). The resulting solution was stirred overnight at 50 C. in an oil bath. The reaction was then quenched by the addition of ice water (1 L). The resulting solution was extracted with ether (3×200 mL), the organic layers combined and dried over anhydrous Na2SO4, filtered and then concentrated to provide the desired product as a yellow oil (12.0 g, crude), which was used as is without further purification. 1H NMR (400 MHz, CDCl3): delta 7.46 (s, 1H), 3.94 (s, 3H) ppm.Add 400 mL of water to a 1 L reaction flask.Compound C (86 g, 0.57 mol), Reduced iron powder (15.96g, 0.285mol), The temperature was controlled to add bromine (242 g, 1.55 mol) at 30 C.After the system is stable, The temperature was raised to 100 C for 4 hours.Cool to room temperature, The reaction solution was poured into 2 L of sodium thiosulfate aqueous solution and stirred.DCM extraction 3 times, Washed with aqueous sodium thiosulfate twice, Dry over anhydrous sodium sulfate, concentrate, Vacuum distillation, External temperature 55 C, Internal temperature 32 C, 0.5 Torr, Got a colorless liquid, Is an azeotrope;The product is cooled and received by ice salt bath.The temperature is 65 C outside the temperature.Internal temperature 58 C, 0.5 Torr, A yellow solid was obtained in 98 g. GC 99%In a 1L reaction bottle, Add anhydrous THF, Compound D (50 g, 0.218 mol), under nitrogen, Cool down to -80 C, Add n-butyl lithium (100 mL, 2.5 M) dropwise and stir for 30 min.Then, isopropanol pinacol borate (41.8 g, 0.225 mol) was added dropwise at -80 C, and the temperature was maintained for 30 min.TLC detects raw materials.The reaction was quenched with 500 mL of a saturated aqueous solution of ammonium chloride.Spin dry THF, Add methyl tert-butyl ether MTBE, padded diatomaceous earth, Divide the organic phase, Wash once with saturated aqueous sodium chloride solution, Dry over anhydrous sodium sulfate, concentrate, Then beat with petroleum ether (PE), Filtration of a white solid 46 g. GC 99%, A mixture of 286 tert-butyldimethyl(4-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolan-2-yl)phenoxy)silane (1.0 g, 3.0 mmol), 288 To a solution of tert-butyl 5-(4, 4, 5, 5-tetramethyl- 1, 3 , 2-dioxaborolan-2-yl)indoline- 1- carboxylate (2.5 g, 7.24 mmol) in dioxane (20 mL) and H20 (4 mE) was added Na2CO3 (1.5 mmol) and 4-bromo-1 -methyl-3-(trifluoromethyl)-IH-pyrazole (1.7 g, 7.24 mmol). The mixture was heated to 120 C for 12 h under a nitrogen atmosphere. After cooling the reaction to room temperature, the mixture was concentrated in vacuo. The crude residue waspurified by silica gel chromatography (petroLeum ether / EtOAc 1: 1) to give the title compound (2.3 g, 86%) as a yellow solid. LCMS MIZ (M+H) 368.[1, 1 ?-bis(diphcnylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (0.64 g, 0.87 mmol) was added to a mixture of 4-bromo-1-methyl-3-(trifluoromethyl)-IH- pyrazole (2.0 g, 8.7 mmol), 2-fluoro-4-(4, 4, 5 , 5-tetramethyl- 1, 3 , 2-dioxaborolan-2-yl)aniline (2.1 g, 8.7 mmol) and Na2CO3 (1.8 g, 17.4 mmol) in 1, 4-dioxane (20 mL) and water (4 mL).The reaction mixture was stirred under nitrogen atmosphere at 120 C for 12 h. After cooling to room temperature the reaction mixture was filtered, concentrated in vacuo and the residue was purified by silica gel chromatography (petroleum ether/EtOAc3:1 to 1:1) to give the title compound (1.2 g, 55%) as a light yellow solid. LCMS MIZ (M+H) 260.

Molecular Weight:229.00
XLogP3:1.8
Hydrogen Bond Acceptor Count:4
Exact Mass:227.95100
Monoisotopic Mass:227.95100
Topological Polar Surface Area:17.8
Heavy Atom Count:11
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes