Phenylacetyl chloride → Morpholine-4-carboxylic acid {6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}amide

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Reaction Steps

2-Phenylacetyl chloride (0.064 ml) was dissolved in acetonitrile (3 ml) under a nitrogen atmosphere, and then potassium thiocyanate (94.8 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 morpholine-4-carboxylic acid [6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl}amide (65.0 mg) in acetonitrile (3 ml) was added thereto, followed by stirring for 1 hr. 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=1:4). Fractions containing the target compound were concentrated to give a residue, which was suspended in diethyl ether (3 ml)-hexane (3 ml). The solid was filtered off and dried under aeration to provide the titled compound (54.4 mg, 54.6%) as white powder.

Provenance & Evidence