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Synthesis of 4‐Aminoquinazolines by Palladium‐Catalyzed Intramolecular Imidoylation of N ‐(2‐Bromoaryl)amidines
Author(s) -
Van Baelen Gitte,
Kuijer Sander,
Rýček Lukáš,
Sergeyev Sergey,
Janssen Elwin,
de Kanter Frans J. J.,
Maes Bert U. W.,
Ruijter Eelco,
Orru Romano V. A.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201102468
Subject(s) - amidine , intramolecular force , isocyanide , palladium , ligand (biochemistry) , catalysis , chemistry , solvent , combinatorial chemistry , coupling reaction , medicinal chemistry , stereochemistry , organic chemistry , biochemistry , receptor
Compared with the widespread use of carbonylative Pd‐catalyzed cross‐coupling reactions, similar reactions involving isocyanide insertion are almost virgin territory. We investigated the intramolecular imidoylative cross‐coupling of N ‐(2‐bromoaryl)amidines, leading to 4‐aminoquinazolines. After thorough optimization of the reaction with respect to palladium source and loading, ligand, base, temperature, and solvent, a small library of 4‐aminoquinazolines was prepared to determine the scope of this method. Various substituents are tolerated on the amidine and the isocyanide, providing efficient access to a broad range of diversely substituted 4‐aminoquinazolines of significant pharmaceutical interest.