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Heterocyclic Merging of Stereochemically Diverse Chiral Piperazines and Morpholines with Indazoles.

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.

SUBMITTER: Viveki AB

PROVIDER: S-EPMC10885319 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Heterocyclic Merging of Stereochemically Diverse Chiral Piperazines and Morpholines with Indazoles.

Viveki Amol B AB Mansfield Timothy M TM Tran Kevin A KA Lenkeit Evan E MacKenzie Kevin R KR Young Damian W DW Chamakuri Srinivas S

Chemistry (Weinheim an der Bergstrasse, Germany) 20230829 55

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 piperazi ...[more]

PMID: 37462979

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