Phenylacetyl isocyanate → 4-(Azetidin-1-ylmethyl)piperidine-1-carboxylic acid {4-[4-(3-phenylacetylureido)phenoxy]pyridin-2-yl}amide

Participants

Reaction Steps

To a solution of 4-(azetidin-1-ylmethyl)piperidine-1-carboxylic acid [4-(4-aminophenoxy)pyridin-2-yl]amide (31 mg) in N,N-dimethylformamide (1 ml) was added a solution of 0.25 M 2-phenylacetyl isocyanate in hexane (0.982 ml) under a nitrogen atmosphere, followed by stirring for 1 hr. 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, then ethyl acetate:methanol=9:1). Fractions containing the target compound were concentrated to give a residue, which was then suspended in diethyl ether (1.5 ml) and hexane (3 ml). The solid was filtered off and dried under aeration to provide the titled compound (28.0 mg, 63.1%) as white powder.

Provenance & Evidence