Ammonium Chloride → N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-N-methyl-3-(trifluoromethyl)-5-(2-(trimethylsilyl)ethylthio)benzamide

Participants

Reaction Conditions

Reaction Steps

A solution of 3-bromo-N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-N-methyl-5-(trifluoromethyl)benzamide (0.59 g, 1.19 mmol) and 2-(trimethylsilyl)ethanethiol (159 mg, 187 μL, 1.19 mmol) in dioxane (5.9 mL) was stirred under argon for 5 minutes in a sealed tube. To the clear, light yellow solution were added tris(dibenzylideneacetone)dipalladium (0) (27.2 mg, 29.7 μmol, CAS RN 52409-22-0), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (34.3 mg, 59.3 μmol, CAS RN 161265-03-8) and DIPEA (307 mg, 414 μL, 2.37 mmol) and the reaction mixture was stirred at 120° C. for 5.5 hours, followed by stirring at room temperature overnight. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified twice by silica gel chromatography on a 20 g column using a MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 50:50). Off-white solid (0.483 g; 73%). MS (ESI): m/z=551.18 [M+H]+.

Provenance & Evidence