Phenylacetyl chloride → 1-(3-Dimethylaminopropyl)-3-{6-[2-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyrimidin-4-yl}-1-methylurea

Participants

Reaction Steps

2-Phenylacetyl chloride (0.032 ml) was dissolved in acetonitrile (3 ml) under a nitrogen atmosphere, and then potassium thiocyanate (46.6 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 ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate were added thereto, followed by stirring for 30 min. The organic layer was separated, 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 dissolved in toluene (1 ml)-ethanol (1 ml), and then a solution of 3-[6-(4-amino-2-fluorophenoxy)pyrimidin-4-yl]-1-(3-diethylaminopropyl)-1-methylurea in toluene (1.5 ml)-ethanol (1.5 ml) was added thereto under a nitrogen atmosphere, followed by stirring at room temperature for 2 hrs. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; heptane:ethyl acetate=1:1). Fractions containing the crude product were concentrated to give a residue, which was then purified by silica gel column chromatography (FUJI Silysia NH, eluent; heptane:ethyl acetate=1:1). Fractions containing the target compound were concentrated to give a residue, which was dried in vacuum to provide the titled compound (6.0 mg, 12.5%) as a white solid.

Provenance & Evidence