SYNTHESIS OF 2,4-DIAMINO-9H-INDENO[2,1-D]PYRIMIDINES

As part of a search for new antifolic, antimalarial, and antitumor agents, a series of 2,4‐diamino‐9H‐indeno[2,1‐d]pyrimidines was prepared by condensation of guanidine with substituted 2‐alkoxy‐3‐cyano‐1H‐indenes. Base‐catalyzed cyclization of 1,2‐bis(cyanomethyl)benzenes afforded 2‐amino‐3‐cyano‐1H‐indenes, which were converted into 3‐cyano‐2‐methoxy‐1H‐indenes by acid hydrolysis and treatment of the resultant 1‐cyano‐2‐indanones with diazomethane. Alternatively, 2‐amino‐3‐cyano‐1H‐indenes could be transformed directly into 2‐ethoxy‐3‐eyano‐1H‐indenes by reaction with ethanol and sulfuric acid. The 2,4‐diamino‐9H‐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. Copyright © 1969 Journal of Heterocyclic Chemistry