Sodium Bicarbonate → 4-(3-Dimethylaminoazetidin-1-yl)piperidine-1-carboxylic acid [4-(4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyridin-2-yl]amide

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Reaction Steps

To a solution of 4-(3-dimethylaminoazetidin-1-yl)piperidine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (60 mg) in tetrahydrofuran (5.0 ml) was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in tetrahydrofuran (0.25 M, 1.75 ml) at room temperature, followed by stirring at room temperature for 0.5 hr. To the reaction mixture was added a saturated aqueous solution of sodium hydrogencarbonate, followed by stirring at room temperature for 0.5 hr. The reaction mixture was extracted with ethyl acetate. The organic layer was washed with brine, 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, then ethyl acetate:methanol=10:1). Fractions containing a target compound were concentrated to give a solid, which was suspended in diethyl ether (1 ml) and hexane (2 ml). The solid was filtered off, washed with diethyl ether:hexane=1:2, and dried under aeration to provide the titled compound (23.2 mg, 27%) as white powder.

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