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Synthesis of Quinazolines via an Iron-Catalyzed Oxidative Amination of N-H Ketimines
Cheng-Yi Chen1, Fengxian He2, Guangrong Tang2
1Janssen R&D, Pharmaceutical Development and Manufacturing Sciences, Small Molecule API Switzerland, Cilag AG , Hochstrasse 201, 8205 Schaffhausen, Switzerland.
Abstract:
An efficient synthesis of quinazolines based on an iron-catalyzed C(sp3)-H oxidation and intramolecular C-N bond formation using tert-BuOOH as the terminal oxidant is described. The reaction of readily available 2-alkylamino benzonitriles with various organometallic reagents led to 2-alkylamino N-H ketimine species. The FeCl2-catalyzed C(sp3)-H oxidation of the alkyl group employing tert-BuOOH followed by intramolecular C-N bond formation and aromatization afforded a wide variety of 2,4-disubstituted quinazolines in good to excellent yields.
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