Hexane → Pyrrolidine-1-carboxylic acid [4-(4-{3-[2-(4-fluorophenyl)acetyl]thioureido}phenoxy)pyridin-2-yl]amide

Participants

Reaction Steps

2-(4-Fluorophenyl)acetyl chloride (72.5 mg) was dissolved in acetonitrile (2 ml) under a nitrogen atmosphere, and then potassium thiocyanate (81.6 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 a solution of 4-(4-aminophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (50 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=1:1 to 1:3). Fractions containing the target compound were concentrated to give a residue, which was suspended in diethyl ether (0.5 ml)-hexane (1.5 ml). The solid was filtered off and dried under aeration to provide the titled compound (15.8 mg, 19.1%) as a pale yellow solid.

Provenance & Evidence