Benzeneacetamide → 4-{2-Fluoro-4-[3-(2-phenylacetyl)ureido]phenoxy}-2-{[4-(pyrrolidin-1-yl)piperidin-1-yl]carbonylamino}pyridine

Participants

Reaction Conditions

Reaction Steps

2-Phenylacetamide (203 mg) was dissolved in 1,2-dichloroethane (20 ml) under a nitrogen atmosphere, and then oxalyl chloride (0.174 ml) was added thereto, followed by stirring at 120° C. overnight. The reaction mixture was concentrated under a reduced pressure to give a residue, which was then dissolved in N,N-dimethylformamide (5 ml) under a nitrogen atmosphere. 4-(4-Amino-2-fluorophenoxy)-2-{[4-(pyrrolidin-1-yl)piperidin-1-yl]carbonylamino}pyridine (295 mg) was then 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 water and brine in this order, 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:methanol=98:2). Fractions containing the target compound were concentrated under a reduced pressure to give a brown powder residue, which was then dissolved in ethyl acetate (10 ml) to extract with 1 N hydrochloric acid (5 ml). To the aqueous layer was added a 1 N aqueous solution of sodium hydroxide dropwise to make it neutral, followed by stirring overnight. The precipitated solid was filtered off, washed with water, and dried under aeration at 60° C. to provide the titled compound (116 mg, 28%) as pale pink powder.

Provenance & Evidence