Diethyl Ether → 3-[3-(2-chloro-4-pyrimidinyl)-8-fluoroimidazo[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) (4.0 g, 10.34 mmol) in DCM (103 mL) at rt under N2 was added NBS (1.84 g, 10.34 mmol). The reaction was stirred approximately 30 min, then concentrated under vacuum to a foam like solid. The solid was dissolved in dioxane (103 mL) and 2-amino-3-fluoropyridine (3.47 g, 31.0 mmol) was added. The reaction was stirred under N2, heated to 80° C., and stirred for approximately 40 h, then cooled to rt. The reaction was diluted with EtOAc (200 mL) and half-saturated aqueous NaHCO3 (150 mL). The organic layer was separated and washed with brine. The combined aqueous layers were extracted with EtOAc (2×). 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 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 (1.58 g, 3.29 mmol, 32%) as a white solid. MS (ESI): 480 [M+H]+.

Provenance & Evidence