Synthesis of 2,4‐diamino‐9<i>H</i>‐indeno[2,1‐<i>d</i>]pyrimidines

Abstract

Abstract As part of a search for new antifolic, antimalarial, and antitumor agents, a series of 2,4‐diamino‐9 H ‐indeno[2,1‐ d ]pyrimidines was prepared by condensation of guanidine with substituted 2‐alkoxy‐3‐cyano‐1 H ‐indenes. Base‐catalyzed cyclization of 1,2‐bis(cyanomethyl)benzenes afforded 2‐amino‐3‐cyano‐1 H ‐indenes, which were converted into 3‐cyano‐2‐methoxy‐1 H ‐indenes by acid hydrolysis and treatment of the resultant 1‐cyano‐2‐indanones with diazomethane. Alternatively, 2‐amino‐3‐cyano‐1 H ‐indenes could be transformed directly into 2‐ethoxy‐3‐eyano‐1 H ‐indenes by reaction with ethanol and sulfuric acid. The 2,4‐diamino‐9 H ‐indeno[2,1‐d]‐pyrimidines represent a new type of planar, tricyclic pyrimethamine analog, in which free rotation of the phenyl and pyrimidine rings is prevented by means of a methylene bridge.