Water → HCID 66729575, compound

Participants

Reaction Conditions

Reaction Steps

N-(3-Bromo-2-fluoro-phenyl)-2,5-difluoro-N-methoxymethyl-benzenesulfonamide (12 g, 29.25 mmol) was dissolved in 1,4-dioxane (156 mL) and argon was bubbled through the solution for 10 minutes. 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (prepared as described in WO2010/010154) (10.6 g, 38.03 mmol, 1.3 eq) was then added, followed by cesium carbonate (9.5 g, 29.25 mmol, 2 eq), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (Pd(dppf)Cl2.CH2Cl2) (1.2 g, 1.46 mmol, 0.05 eq) and water (0.9 mL) and the reaction mixture was heated to 100° C. and stirred at this temperature for 2 h. A further addition of 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (4 g, 0.5 eq) was made and heating was continued for 2 h. The mixture was then concentrated under reduced pressure, taken up with AcOEt (200 mL) and filtered over a Celite pad. The filtrate was washed with water and brine, dried over Na2SO4 and evaporated to dryness. The crude was purified by chromatography on silica gel (cyclohexane/AcOEt 7:3) to give 18 g of 2,5-difluoro-N-{2-fluoro-3-[2-(tetrahydro-pyran-2-yl)-2H-pyrazol-3-yl]-phenyl}-N-methoxymethyl-benzene-sulfonamide contaminated by N-tetrahydropyranylpyrazole.

Provenance & Evidence