Hexane → 1-[1-(2-Dimethylaminoethyl)piperidin-4-yl]-3-{6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}-1-methylurea

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Reaction Steps

To a solution of 3-[6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]-1-[1-(2-dimethylaminoethyl)piperidin-4-yl]-1-methylurea (110 mg) in ethanol (2.0 ml) was added (1S)-(+)-10-camphorsulfonic acid (101 mg), followed by stirring at room temperature for 15 min. A solution of 2-phenylacetyl isothiocyanate in toluene (0.25 M, 3.06 ml) was added to the reaction mixture, followed by stirring at room temperature for 2 hrs. The reaction mixture was partitioned between ethyl acetate (30 ml) and a saturated aqueous solution of sodium hydrogencarbonate (10 ml). 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, ethyl acetate:methanol=20:1, then 10:1). Fractions containing a target compound were concentrated to give a solid, which was suspended in diethyl ether:hexane=1:1. The solid was filtered off, and washed with diethyl ether to provide the titled compound (25.3 mg, 16.3%) as pale yellow powder.

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