Heterocyclic Merging of Stereochemically Diverse Chiral Piperazines and Morpholines with Indazoles

Authors

Amol B Viveki
Timothy M Mansfield
Kevin A Tran
Evan Lenkeit
Kevin R MacKenzie
Damian W Young
Srinivas Chamakuri

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.

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