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Updated: Dec 21, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Synthesis of Quinazolin-4-ones by Copper-Catalyzed Isocyanide Insertion
Jurriën W Collet1,2, Edith A van der Nol1, Tom R Roose1
1Department of Chemistry and Pharmaceutical Sciences and Amsterdam Institute for Molecules, Medicines & Systems (AIMMS), Vrije Universiteit Amsterdam, De Boelelaan 1108, 1081 HZ Amsterdam, The Netherlands, Web: www.syborch.com.
Abstract:
Herein, we report a novel copper-catalyzed imidoylative cross-coupling/cyclocondensation reaction between 2-isocyanobenzoates and amines efficiently producing quinazolin-4-ones. The reaction utilizes Cu(II) acetate as an environmentally benign catalyst in combination with a mild base and proceeds well in anisole, a recommended, sustainable solvent. Additionally, the reaction does not require dry conditions or inert atmospheres for optimal performance. The scope of this isocyanide insertion reaction is rather broad, tolerating various functionalized isocyanobenzoates and a range of substituted amines, although the use of aromatic amines as nucleophiles requires microwave heating.
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