Development of the Synthetic Route to PF-06878031 Part 1: Selective Alkylation Route

The target compound PF-06878031 is a key structural fragment of a range of oral late-stage glucagon-like peptide-1 receptor agonists (GLP-1-RA) under development in our laboratories for the indications of type-2 diabetes mellitus (T2DM) and weight loss. This article describes the identification of a...

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Published inOrganic process research & development Vol. 28; no. 7; pp. 2433 - 2445
Main Authors Brea, Oriana, Buck, Julia, Carson, Nessa, Derrick, Andrew M., Fussell, Steven J., Gymer, Adam E. S., Hawksworth, Michael, Hopkins, Adam W., Ingram, Heather, Johnson, Rebecca A., Laity, Daniel A., Mathew, Jinu S., Moses, Ian B., Rellegue, James, Rose, Emily K., Twiddle, Steven J. R., West, Adam
Format Journal Article
LanguageEnglish
Published American Chemical Society 19.07.2024
Subjects
selective alkylation
chlorination
thermal amidation
hydrogenation
oxetane
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Summary:The target compound PF-06878031 is a key structural fragment of a range of oral late-stage glucagon-like peptide-1 receptor agonists (GLP-1-RA) under development in our laboratories for the indications of type-2 diabetes mellitus (T2DM) and weight loss. This article describes the identification of a selective alkylation route and development of a process, capable of delivering multikilo quantities of PF-06878031. Process development afforded improved safety, increased yield, reduced step count, and lowered PMI. The new process has been scaled up at multiple facilities to generate >1.5MT of high purity PF-06878031.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.4c00053