Publication Date
10-2-2023
Journal
Chemistry
DOI
10.1002/chem.202301888
PMID
37462979
PMCID
PMC10885319
PubMedCentral® Posted Date
2-23-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
chiral morpholines, chiral piperazines, fused heterocycles, indazoles, scaffold merging
Abstract
We report a heterocyclic merging approach to construct novel indazolo-piperazines and indazolo-morpholines. Starting from chiral diamines and amino alcohols, novel regiochemically (1,3 and 1,4) and stereochemically diverse (relative and absolute) cohorts of indazolo-piperazines and indazolo-morpholines were obtained within six or seven steps. The key transformations involved are a Smiles rearrangement to generate the indazole core structure and a late-stage Michael addition to build the piperazine and morpholine heterocycles. We further explored additional vector diversity by incorporating substitutions on the indazole aromatic ring, generating a total of 20 unique, enantiomerically pure heterocyclic scaffolds.
Graphical Abstract
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