Metathesis Reactions

Thiel, Oliver R.

doi:10.1002/9781118309872.ch5

Cited by 5 publications

(1 citation statement)

References 150 publications

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“…Ring-closing metathesis (RCM) reactions are powerful tools that are widely used in synthesis since they provide access to carbocyclic and heterocyclic rings with three-dimensional topologies that are useful in the design of bioactive compounds . These tools have gained popularity in the synthetic community, as they enable chemists to access these structures on the process scale .…”

Section: Introductionmentioning

confidence: 99%

Accelerated Development of a Scalable Ring-Closing Metathesis to Manufacture AMG 176 Using a Combined High-Throughput Experimentation and Computational Modeling Approach

St‐Pierre

Cherney

Chen

et al. 2020

Org. Process Res. Dev.

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AMG 176 is a drug candidate in our oncology pipeline. Ring-closing metathesis (RCM) is a key reaction in the AMG 176 synthesis that is used to construct the 16-membered macrocycle. Process intensification was executed on a compressed timeline by combining high-throughput experimentation and computational analysis using density functional theory, which led to the identification of an optimal 4-bromobenzoate protecting group on the allylic alcohol moiety. Comprehensive process improvements led to a reduction in reaction volume from 800 to 50 L/kg with a >20% yield improvement compared with the discovery route. The RCM process developed from these studies was instrumental in the clinical advancement of the AMG 176 program.

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Section: Introductionmentioning

confidence: 99%