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Updated: Jan 29, 2026

Optimization of the Ugi Reaction Using Parallel Synthesis and Automated Liquid Handling
Published on: November 11, 2008
Telescoped synthesis of C3-functionalized (E)-arylamidines using Ugi-Mumm and regiospecific quinazolinone
Victor A Jaffett1, Alok Nerurkar, Xufeng Cao
1Department of Chemistry, University of Wisconsin, 1101 University Ave., Madison, WI 53706, USA. jennifer.golden@wisc.edu.
Abstract:
An efficient four-step, six-transformation protocol was developed to afford bioactive N-alkyl- or N-arylamide (E)-arylamidines featuring strategic amidine C3 modifications which were inaccessible or low yielding by previous methods. This synthetic approach, exemplified with 24 amidines and requiring only a single purification, highlights a multicomponent Ugi-Mumm rearrangement to afford highly diversified quinazolinones which undergo regiospecific rearrangement to afford new amidines. The method extensively broadens the structural scope of this new class of trisubstituted amidines and demonstrates the tolerance of regional C3 amidine steric bulk, visualized with X-ray crystallographic analysis.
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