Short Scalable Route to Bis-morpholine Spiroacetals and Oxazepane Analogues: Useful 3D-Scaffolds for Compound Library Assembly.

ABSTRACT: sp³-Rich molecular scaffolds incorporating nitrogen heterocycles represent important starting points for assembling compound screening libraries and drug discovery. Herein, we report a four-step synthesis of a conformationally well-defined sp³-rich scaffold incorporating two morpholine rings embedded within a spiroacetal framework. The synthesis involves the intermediacy of a 2-chloromethyl-substituted morpholine, accessed from epichlorohydrin and readily available β-aminoalcohols. Base-mediated dehydrochlorination affords an exocyclic enol ether, from which the second morpholine ring is constructed in two steps. Scaffold synthesis is high-yielding and can be performed on a large scale. The methodology allows ready substitution of one-or both- of the morpholine rings

SUBMITTER: Kovari D 

PROVIDER: S-EPMC11852203 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature