Phenylacetyl chloride → Pyrrolidine-1-carboxylic acid {4-[3-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyridin-2-yl}amide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-phenylacetyl chloride (0.054 ml, 0.43 mmol) in acetonitrile (4.3 ml) was added potassium thiocyanate (83 mg) at room temperature, followed by stirring under a nitrogen atmosphere at 60° C. for 1.5 hrs. The reaction mixture was cooled in an ice bath, and then a solution of pyrrolidine-1-carboxylic acid [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]amide (90 mg) in acetonitrile (4.0 ml) was added thereto, followed by warming the reaction mixture to room temperature and stirring for 3 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 (eluent; hexane:ethyl acetate=1:1 to 1:2, then ethyl acetate). Fractions containing the target compound were concentrated to give a solid, which was suspended in diethyl ether. The solid was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (18 mg, 13%) as colorless powder.

Provenance & Evidence