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Updated: Jul 11, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Aerobic Dehydrogenative Aromatization in the Preparation of 4-Aminoquinoline Derivatives by Synergistic Pd/Cu
Fei Chen1, Huidan Geng1, Chun Li1
1School of Pharmacy, Guizhou Provincial Engineering Technology Research Center for Chemical Drug R&D, Guizhou Medical University, 550014 Guiyang, P. R. China.
Abstract:
The 4-aminoquinoline moiety is widely present in various bioactive compounds and marketed drugs, while the preparation of this target structure relies heavily on the amination of 4-chloroquinolines. Herein, an atom and step economic procedure was developed based on an aerobic dehydrogenative aromatization strategy. Unlike the well-known palladium-catalyzed dehydrogenative aromatization of cyclohexanones with amines, synergistic Pd/Cu catalysis is crucial for 2,3-dihydroquinolin-4(1H)-one type of substrates. Under the optimized conditions, a range of aromatic/aliphatic amines and 2,3-dihydroquinolin-4(1H)-ones were coupled to give the corresponding 4-aminoquinoline products in moderate to high yields, and the application of the current methodology for the preparation and late-stage diversification of marketed drugs was also demonstrated.
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