A Single Quadrupole Compact Mass Spectrometer Enabling Early Stage Synthetic Optimization of Verubecestat (MK-8931)

A low-cost compact mass spectrometer was effectively utilized for identifying and tracking process impurities in the early stage development of a multistep synthetic protocol used to prepare the verubecestat drug substance. Process optimizations were influenced by the type, quantity, and final fate...

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Bibliographic Details
Published inOrganic process research & development Vol. 23; no. 12; pp. 2758 - 2763
Main Authors Zewge, Daniel, Bu, Xiaodong, Zhang, Li, Thaisrivongs, David, Xu, Yanke, Gong, Xiaoyi
Format Journal Article
LanguageEnglish
Published American Chemical Society 20.12.2019
Subjects
process chemistry development
compact mass spectrometer
impurity identification
verubecestat
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Summary:A low-cost compact mass spectrometer was effectively utilized for identifying and tracking process impurities in the early stage development of a multistep synthetic protocol used to prepare the verubecestat drug substance. Process optimizations were influenced by the type, quantity, and final fate of impurities generated during synthesis. Employing a compact mass spectrometer for impurity identification and tracking served as a guide to redesign synthetic strategies which enabled the minimization or avoidance of undesired side products.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.9b00370