Development of a Practical Large-Scale Synthesis of Denagliptin Tosylate

被引：42

作者：

Patterson, Daniel E. ^{[1
]}

Powers, Jeremiah D. ^{[1
]}

LeBlanc, Michael ^{[1
]}

Sharkey, Tyler ^{[1
]}

Boehler, Emily ^{[1
]}

Irdam, Erwin ^{[1
]}

Osterhout, Martin H. ^{[1
]}

机构：

[1] GlaxoSmithKline Inc, Chem Dev, Res Triangle Pk, NC 27709 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2009年 / 13卷 / 05期

关键词：

DIPEPTIDYL-PEPTIDASE-IV; REAGENT; INHIBITORS; DISCOVERY; CATALYST; POTENT; ACIDS;

D O I：

10.1021/op900178d

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

A large-scale synthesis of denagliptin tosylate has been developed. The efficiency of the synthesis has been improved from the initially scaled route by changing the order of steps (performing a dehydration at a late stage). The key step of the synthesis is a single-step peptide coupling/dehydration, mediated by n-propanephosphonic acid cyclic anhydride. The challenges of developing this synthesis into a robust and practical manufacturing route are described.

引用

页码：900 / 906

页数：7

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