Cheng-Yi Chen1, Fengxian He2, Guangrong Tang2, Huiqing Yuan2, Ning Li2, Jinmin Wang2, Roger Faessler1. 1. Janssen R&D, Pharmaceutical Development and Manufacturing Sciences, Small Molecule API Switzerland, Cilag AG , Hochstrasse 201, 8205 Schaffhausen, Switzerland. 2. Porton (Shanghai) R&D Center , 1299 Ziyue Road, Zizhu Science Park, Minhang District, Shanghai 200241, China.
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.
An efficient synthesis of quinazolines based on ann class="Chemical">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.