P-Toluic Acid → 1-(3-[2-[4-(2,4-Dioxothiazolidin-5-ylmethyl)phenoxymethyl]-1-methyl-1H-benzimidazol-6-yloxy]phenyl)-3-p-tolylurea

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

A mixture of p-toluic acid (109 mg), diphenylphosphoryl azide (209 mg), triethylamine (314 mg) and anhydrous toluene (8 ml) was stirred at 80° C. for 1 hour. To the reaction mixture was added 5-[4-[6-(3-aminophenoxy)-1-methyl-1H-benzimidazol-2-ylmethoxy]benzyl]thiazolidine-2,4-dione dihydrochloride (400 mg) and anhydrous N,N-dimethylformamide (4 ml) at room temperature and the mixture was stirred at the same temperature for 2.5 hours. The reaction mixture was concentrated and partitioned between ethyl acetate and water. The extract was washed with saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and then concentrated. The residue was chromatographed on a silica gel column using ethyl acetate:n-hexane=3/2→3/1→ethyl acetate as the eluant. The product insoluble in methanol was isolated by filtration and further purified by preparative reverse phase high performance liquid chromatography using acetonitrile:water=50:50→55:45→60:40 as the eluant to afford the title compound (27 mg, mp 173.0-175.2° C.).

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