Cesium carbonate → N-[6-(4-amino-2-chlorophenoxy)imidazo[1,2-a]pyridin-2-yl]cyclopropanecarboxamide

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Reaction Steps

To a solution of N-(6-hydroxyimidazo[1,2-a]pyridin-2-yl)cyclopropanecarboxamide (200 mg, 0.921 mmol) and 4-fluoro-3-chloro-1-nitrobenzene (193 mg, 1.11 mmol) in dimethyl sulfoxide (2 mL) was added cesium carbonate (450 mg, 1.38 mmol), and the mixture was stirred at room temperature for 6 hr. Ethyl acetate and saturated aqueous ammonium chloride solution were added to the reaction mixture, and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed with saturated brine, and the solvent was evaporated under reduced pressure. A mixed solution of the obtained residue, reduced iron (271 mg, 4.61 mmol) and ammonium chloride (493 mg, 9.21 mmol) in ethanol (2 mL)/tetrahydrofuran (2 mL)/water (1 mL) was stirred at 80° C. for 7 hr. The reaction mixture was diluted with ethyl acetate and tetrahydrofuran, and filtered through celite. Water was added to the filtrate, and the mixture was extracted twice with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=2/1→ethyl acetate alone) to give the title compound (177.5 mg, 56%) as a white solid.

Provenance & Evidence