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Synthesis of 2,4‐diamino‐9 H ‐indeno[2,1‐ d ]pyrimidines
Author(s) -
Rosowsky Andre,
Dey Adrienne S.,
Battaglia Josephine,
Modest Edward J.
Publication year - 1969
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570060503
Subject(s) - chemistry , diazomethane , guanidine , pyrimidine , stereochemistry , hydrolysis , methylene , medicinal chemistry , sulfuric acid , alkoxy group , ethanol , organic chemistry , alkyl
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.