Diethyl Ether → 4-(1-Methylazetidin-3-yl)piperazine-1-carboxylic acid [4-(2-fluoro-4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyridin-2-yl]amide

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Reaction Steps

To a solution of 4-(1-methylazetidin-3-yl)piperazine-1-carboxylic acid [4-(4-amino-2-fluorophenoxy)pyridin-2-yl]amide (40.0 mg) in tetrahydrofuran (15 ml) was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in ethyl acetate (0.25 M, 1.60 ml), followed by stirring at room temperature for 1 hr. To the reaction mixture was added a saturated aqueous solution of sodium hydrogencarbonate, followed by stirring at room temperature for 15 min. The organic layer was separated, and dried over anhydrous sodium sulfate. The organic layer was concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; ethyl acetate, ethyl acetate:methanol=20:1, then 10:1). Fractions containing a target compound were concentrated to give a solid, to which diethyl ether (1 ml) and hexane (1 ml) were added to suspend. The solid was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (18.5 mg, 31.9%) as pale yellow powder.

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