Diethyl Ether → 3-[6-(2-Fluoro-4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyrimidin-4-yl]-1,1-dimethylurea

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Reaction Conditions

Reaction Steps

2-(4-Fluorophenyl)acetamide (125 mg) was dissolved in 1,2-dichloroethane (9 ml) under a nitrogen atmosphere, and then oxalyl chloride (0.10 ml) was added thereto, followed by stirring at 110° C. overnight. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (1 ml) under a nitrogen atmosphere. A solution of 3-[6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]-1,1-dimethylurea (90 mg) in N,N-dimethylformamide (2 ml) was then added thereto, followed by stirring for 30 min. The reaction mixture was partitioned between ethyl acetate and water. 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; hexane:ethyl acetate=1:3). Fractions containing the target compound were concentrated to give a residue, to which diethyl ether (2 ml)-hexane (1 ml) was added to suspend. The solid was filtered off and dried under aeration to provide the titled compound (72.4 mg, 49.8%) as a pale yellow solid.

Provenance & Evidence