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Updated: Aug 26, 2025

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Dihydropyrazinoquinazolinones via SN2 Sulfamidate Ring-Opening and a Sequential Quinazolinone-Amidine Rearrangement
Jhewelle N Fitz-Henley1, Soren D Rozema1, Jennifer E Golden1
1Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin─Madison, 777 Highland Avenue, Madison, Wisconsin 53705, United States.
Abstract:
A synthesis of dihydropyrazino-[2,1-b]-quinazolinones is described using a 2-alkylaminoquinazolinone-mediated ring opening of a-/chiral sulfamidates, followed by a tandem quinazolinone-amidine rearrangement termed SQuAReS. This approach takes advantage of sulfamidates whose regioselective ring opening, after hydrolysis, appends an optimally distanced nucleophilic amine to a quinazolinone such that subsequent domino rearrangements are favored, integrating unique substitution patterns on a privileged core. This three-step protocol integrated five telescoped transformations and generated 20 pyrazinoquinazolinones in up to 74% yield with high enantiomeric fidelity and diastereoselectivity.
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