2-(4-Fluorophenyl)acetyl isocyanate → 4-(Pyrrolidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-{3-[2-(4-fluorophenyl)acetyl]ureido}phenoxy)pyridin-2-yl]amide

Participants

Reaction Steps

To a solution of 4-(pyrrolidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (50 mg) in N,N-dimethylformamide (1.5 ml) was added a solution of 0.25 M 2-(4-fluorophenyl)acetyl isocyanate in ethyl acetate (1.51 ml) under a nitrogen atmosphere, followed by stirring for 17 hrs. The reaction mixture was partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (50 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml), brine (50 ml) 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; ethyl acetate). Fractions containing the target compound were concentrated to give a residue, which was then suspended in ethyl acetate (1.5 ml) and hexane (1.5 ml). The solid was filtered off and dried under aeration to provide the titled compound (45.7 mg, 63.1%) as white powder.

Provenance & Evidence