Hexane → 3-[3-(2-chloro-4-pyrimidinyl)-7-(trifluoromethyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)benzamide

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Reaction Conditions

Reaction Steps

To a stirred solution of 3-[(2-chloro-4-pyrimidinyl)acetyl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1, step B) (0.4 g, 1.03 mmol) in DCM (10 mL) at rt under N2 was added NBS (0.193 g, 1.09 mmol). The reaction was stirred approximately 30 min, then concentrated under vacuum to a foam like solid. The solid was dissolved in dioxane (10 mL) and 4-(trifluoromethyl)-2-pyridinamine (0.5 g, 3.10 mmol) was added. The reaction was stirred under nitrogen, heated to 80° C., and stirred for approximately 48 h, then cooled to rt. The reaction was diluted with EtOAc and half-saturated aqueous NaHCO3. The organic layer was separated and washed brine. The combined aqueous layers were extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography to give a yellow solid. The solid was dissolved in minimal DCM and hexane was added until a precipitate formed. The slurry was filtered, washing the solids with cold hexane. The solids were dried under vacuum, however proton NMR indicates impurities so the solid was dissolved in minimal DCM and ether was added until a precipitate formed. The slurry was filtered, washing the solids with cold ether. The solids were dried under vacuum to give the title compound of step A (0.250 g, 0.47 mmol, 46%) as a white solid. MS (ESI): 530 [M+H]+.

Provenance & Evidence