Optimized Synthesis of an Abemaciclib Intermediate: Improved Conditions for a Miyaura Borylation/Suzuki Coupling Process
Improved reaction conditions have been developed for a telescoped Miyaura borylation/Suzuki coupling process, which is utilized in the synthesis of an abemaciclib intermediate. Key improvements include the in situ generation of a lipophilic base and tailored ligand selection for each palladium-catalyzed step. Optimizing ligand choice significantly reduced aryl scrambling, a major source of impurities in the borylation step. Additionally, the process improvements led to shortened reaction times and lower palladium loadings, resulting in a more efficient, higher-yielding process.
Authors
- Nachimuthu Muniraj (ORCID: https://orcid.org/0000-0003-4728-6141)
- Michael P. Carroll (ORCID: https://orcid.org/0000-0001-9743-4830)
- Michael M. Murray (ORCID: https://orcid.org/0000-0003-0156-5022)
- A. J. Rogers (ORCID: https://orcid.org/0000-0002-4990-8648)
- Aobha Hickey
- K. O’Sullivan (ORCID: https://orcid.org/0009-0001-4653-7853)
- Cáoimhe J. Niland (ORCID: https://orcid.org/0000-0002-7416-5081)
- Rachel A. O’Sullivan
- Patrick J. Guiry
Institutions
- University College Dublin (IE)
- Eli Lilly (Ireland) (IE)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2024-11-07
- DOI
- https://doi.org/10.1021/acs.oprd.4c00381
- Citations
- 1
- Primary Topic
- Advanced Breast Cancer Therapies
- Type
- article
- Field-Weighted Citation Impact
- 0.42
Funders
- Eli Lilly and Company