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Updated: Jun 8, 2025

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
Published on: August 22, 2018
Mannich-Type Condensation and Domino Quinazolinone-Amidine Rearrangement Affords Ring-Fused Mackinazolinones with
Matthew S Lish1, Jillian E Milanes2, Kyana M Sanders1,3
1Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin, 53706, United States.
Abstract:
A three-step synthesis of anti-amoebic, ring-fused mackinazolinones has been developed. A Mannich-type reaction between quinazolin-4-ones and N-Cbz propanal in the presence of AgOTf afforded quinazolinones (19-94% isolated yield) bearing a newly formed heterocycle with an alkylamine appendage that, upon N-Cbz deprotection and basification, triggered a domino rearrangement to afford 45 separable, ring-fused products. Several compounds inhibited growth of Naegleria fowleri parasites that can cause a lethal human brain infection. Thus, the methodology provides immediate access to a promising anti-amoebic scaffold.
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