Dihydropyrazinoquinazolinones via S_N2 Sulfamidate Ring-Opening and a Sequential Quinazolinone-Amidine Rearrangement Strategy (SQuAReS).

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.

SUBMITTER: Fitz-Henley JN 

PROVIDER: S-EPMC9795801 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature