Developing an atroposelective dynamic kinetic resolution of MRTX1719 by resolving incompatible chemical operations

A high-yielding protocol for atropisomeric resolution was developed by rectifying incompatibilities between crystallization and epimerization via continuous processing. Application toward synthesis of MRTX1719, a densely functionalized active pharmaceutical ingredient (API), improved yield from 37%...

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Bibliographic Details
Published in:Chemical communications (Cambridge, England) England), 2022-09, Vol.58 (74), p.1365-1367
Main Authors: Achmatowicz, Michal M, Chen, Cheng-yi, Snead, David R
Format: Article
Language:English
Subjects:
Crystallization
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Summary:A high-yielding protocol for atropisomeric resolution was developed by rectifying incompatibilities between crystallization and epimerization via continuous processing. Application toward synthesis of MRTX1719, a densely functionalized active pharmaceutical ingredient (API), improved yield from 37% to 87%. This protocol provides a complementary means to access rotamers which challenge current asymmetric methodologies, and greatly improves sustainability by decreasing the consumption of solvent and advanced synthetic intermediates. Continuous SPACE-DKR gives a strategy for high-yielding resolution of atropisomers. This is especially useful for compounds which are difficult to access through traditional asymmetric methodologies. Inherently conflicting reaction conditions are resolved with continuous flow.
ISSN:1359-7345
1364-548X
DOI:10.1039/d2cc03627d