Hexane → Morpholine-4-carboxylic acid [6-[2-fluoro-4-{3-[2-(4-fluorophenyl)acetyl]thioureido}phenoxy)pyrimidin-4-yl]amide

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Reaction Steps

2-(4-Fluorophenyl)acetyl chloride (103 mg) was dissolved in acetonitrile (3 ml) under a nitrogen atmosphere, and then potassium thiocyanate (116 mg) was added thereto at 60° C., followed by stirring at the same temperature for 2 hrs. The reaction mixture was cooled down to room temperature, and then a solution of 4-(4-amino-2-fluorophenoxy)-6-[(morpholin-4-yl)carbonylamino]pyrimidine (79.5 mg) in acetonitrile (3 ml) was added thereto, followed by stirring for 10 min. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. 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 under a reduced pressure 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, which was suspended in diethyl ether (5 ml)-hexane (5 ml). The solid was filtered off and dried under aeration to provide the titled compound (71.9 mg, 56.9%) as a pale yellow solid.

Provenance & Evidence