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Updated: May 13, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
A Van Leusen deprotection-cyclization strategy as a fast entry into two imidazoquinoxaline families
Fabio De Moliner1, Christopher Hulme
1Department of Pharmacology and Toxicology, College of Pharmacy, BIO5 Oro Valley, The University of Arizona, 1580 E. Hanley Blvd., Oro Valley, Arizona 85737, USA.
Abstract:
A concise synthesis of two pharmacologically relevant classes of molecules possessing the imidazoquinoxaline core is reported. The protocol involves use of 1,2-phenylenediamines and glyoxylic acid derivatives, namely ethyl glyoxylate or benzylglyoxamide, along with tosylmethylisocyanides in a microwave-assisted Van Leusen three-component condensation. Subsequent unmasking (Boc removal) of an internal amino-nucleophile promotes deprotection and cyclization that take place either spontaneously in a one-pot fashion to give 8 or upon acidic treatment under microwave irradiation after isolation of the imidazole intermediate to give 11. Of note, a tricyclic framework is hence assembled by means of a rapid and straightforward method with a high bond-forming efficiency.
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