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

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Reaction Steps

Pyrrolidine-1-carboxylic acid [4-(4-amino-3-chlorophenoxy)pyridin-2-yl]amide (79.6 mg) was dissolved in N,N-dimethylformamide (1.5 ml) under a nitrogen atmosphere, and then N-(4-fluorophenyl)malonic acid (142 mg), triethylamine (0.100 ml), and (1H-1,2,3-benzotriazol-1-yloxy)[tri(dimethylamino)]phosphonium hexafluorophosphate (318 mg) were added thereto at 50° C., followed by stirring at the same temperature for 2 hrs and 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, 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; ethyl acetate). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (5 ml)-hexane (5 ml) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (94.5 mg, 76.9%) as white powder.

Provenance & Evidence