Kinetic and Mechanistic Insight into the Thermodynamic Degradation of Saxagliptin

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• 作者：G. Scott Jones ; Scott A. Savage ; Sabrina Ivy ; Patrick L. Benitez ; Antonio Ramirez
• 刊名：Journal of Organic Chemistry
• 出版年：2011
• 出版时间：December 16, 2011
• 年：2011
• 卷：76
• 期：24
• 页码：10332-10337
• 全文大小：308K
• 年卷期：v.76,no.24(December 16, 2011)
• ISSN：1520-6904

文摘

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.