Diethyl Ether → N-(4-Fluorophenyl)-N'-(4-{2-[(pyrrolidine-1-carbonyl)amino]pyridin-4-yloxy}phenyl)malonamide

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Reaction Steps

4-(4-Aminophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (30 mg) was dissolved in N,N-dimethylformamide (1 ml) under a nitrogen atmosphere, and then N-(4-fluorophenyl)malonic acid (59.5 mg), triethylamine (0.042 ml) and (1H-1,2,3-benzotriazol-1-yloxy)[tri(dimethylamino)]phosphonium hexafluorophosphate (134 mg) were added thereto at 50° C., followed by stirring at the same temperature for 30 min. The reaction mixture was cooled down to room temperature, and partitioned between ethyl acetate and a 1 N aqueous solution of sodium hydroxide. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, a saturated aqueous solution of ammonium chloride, water and brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:5, then ethyl acetate). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (2 ml)-hexane (2 ml) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (40.4 mg, 83.4%) as a pale brown solid.

Provenance & Evidence