N-bromobutanimide → 5-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 3-[(2-chloro-4-pyrimidinyl)acetyl]-N-(2,6-difluorophenyl)-4-(methyloxy)benzamide (Intermediate Example 2, step E) (0.950 g, 2.28 mmol) in dichloromethane (23 mL) at rt under N2 was added NBS (0.426 g, 2.39 mmol). The reaction was stirred approximately 30 min, then concentrated under vacuum to a foam like solid. The solid was dissolved in dioxane (23 mL) and 4-fluoro-2-pyridinamine (Example 194, step A) (0.765 g, 6.83 mmol) was added. The reaction was stirred under N2, heated to 80° C., and stirred for approximately 16 h, then cooled to rt. The reaction was diluted with EtOAc and half-saturated aqueous NaHCO3. 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 the title compound of step A (0.700 g, 1.37 mmol, 61%) as a light tan solid. MS (ESI): 510 [M+H]+.

Provenance & Evidence