Kinetic and Mechanistic Insight into the Thermodynamic Degradation of Saxagliptin
The dipeptidyl peptidase-IV inhibitor saxagliptin (Onglyza) can undergo a thermodynamically favored cyclization to form the corresponding cyclic amidine. The kinetics and mechanism of this conversion were examined to develop a commercial synthesis that afforded saxagliptin with only trace levels of...
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Published in | Journal of organic chemistry Vol. 76; no. 24; pp. 10332 - 10337 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
16.12.2011
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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Summary: | The dipeptidyl peptidase-IV inhibitor saxagliptin (Onglyza) can undergo a thermodynamically favored cyclization to form the corresponding cyclic amidine. The kinetics and mechanism of this conversion were examined to develop a commercial synthesis that afforded saxagliptin with only trace levels of this key byproduct. Important findings of this work are the identification of a profound solvent effect and the determination of an autocatalytic pathway. Both of these phenomena result from transition structures involving proton transfer. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3263 1520-6904 |
DOI: | 10.1021/jo202052a |