2-(4-Fluorophenyl)acetic acid → 8-(4-Fluorobenzyl)-3-[2-(4-nitrophenyl)ethyl]-1-propylxanthine

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Reaction Steps

By the method of Example 2, 4-fluorophenylacetic acid is reacted with 5,6-diamino-1-[2-(4-nitrophenyl)ethyl]-3-propyluracil (6) to yield 8-(4-fluorobenzyl)-3-[2-(4-nitrophenyl)ethyl]-1-propylxanthine. By the methods of Example 3 and Example 4, 8-(4-fluorobenzyl)-3-[2-(4-nitrophenyl)ethyl]-1-propylxanthine is alkylated with a mixture of 1,2-dichloroethane and 2-(ethylamino)ethanol, to afford 7-[2-ethyl(2-hydroxyethyl)amino]ethyl-8-(4-fluorobenzyl-3-[2-(4-nitrophenyl)ethyl]-1-propylxanthine, which, in turn, is reduced with hydrazine hydrate or hydrogen gas in the presence of a palladium catalyst to yield 3-[2-(4-aminophenyl)ethyl]-7-[2-ethyl(2-hydroxyethyl)amino]ethyl-8-(4-fluorobenzyl)-1-propylxanthine free base. The corresponding dihydrochloride salt is then made on exposure to an excess of hydrogen chloride in solution.

Provenance & Evidence