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

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Reaction Conditions

Reaction Steps

2-Phenylacetamide (128 mg) was dissolved in 1,2-dichloroethane (10 ml) under a nitrogen atmosphere, and then oxalyl chloride (0.103 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 (3.2 ml) under a nitrogen atmosphere. 4-(4-amino-2-fluorophenoxy)-2-[(pyrrolidin-1-yl)carbonylamino]pyridine (100 mg) was then added thereto, followed by stirring for 30 min. 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 purified by silica gel column chromatography (FUJI Silysia NH, eluent; hexane:ethyl acetate=1:3). Fractions containing the target compound were concentrated to give a residue, to which ethyl acetate (2 ml)-hexane (10 ml) was added to precipitate crystals. The crystals were filtered off and dried under aeration to provide the titled compound (113 mg, 75%) as white crystals.

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