Development of a Practical Large-Scale Synthesis of Denagliptin Tosylate

被引：44

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

共 18 条

[1] Efficient asymmetric synthesis of N-[(1R)-6-chloro-2,3,4,9-tetrahydro-1H-carbazol-1-yl]-2-pyridinecarboxamide for treatment of human papillomavirus infections [J].

Boggs, Sharon D. ;

Cobb, Jeremy D. ;

Gudmundsson, Kristjan S. ;

Jones, Lynda A. ;

Matsuoka, Richard T. ;

Millar, Alan ;

Patterson, Daniel E. ;

Samano, Vicente ;

Trone, Mark D. ;

Xie, Shiping ;

Zhou, Xiao-Ming .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2007, 11 (03) :539-545

[2] Synthesis of (S)-, (R)-, and (rac)-2-amino-3,3-bis(4-fluorophenyl)propanoic acids and an evaluation of the DPP IV inhibitory activity of Denagliptin diastereomers [J].

Deng, Guanghui ;

Ye, Deju ;

Li, Yuanyuan ;

He, Lingyan ;

Zhou, Yu ;

Wang, Jiang ;

Li, Jia ;

Jiang, Hualiang ;

Liu, Hong .

TETRAHEDRON, 2008, 64 (46) :10512-10516

[3] Simple and efficient syntheses of Boc- and Fmoc-protected 4(R)- and 4(S)-fluoroproline solely from 4(R)-hydroxyproline [J].

Doi, M ;

Nishi, Y ;

Kiritoshi, N ;

Iwata, T ;

Nago, M ;

Nakano, H ;

Uchiyama, S ;

Nakazawa, T ;

Wakamiya, T ;

Kobayashi, Y .

TETRAHEDRON, 2002, 58 (42) :8453-8459

[4] A comparison of catalysts to promote imidazolide couplings including the identification of 2-hydroxy-5-nitropyridine as a new, safe, and effective catalyst [J].

Dunn, PJ ;

Hoffmann, W ;

Kang, Y ;

Mitchell, JC ;

Snowden, MJ .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2005, 9 (06) :956-961

[5] Discovery of alogliptin: A potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV [J].

Feng, Jun ;

Zhang, Zhiyuan ;

Wallace, Michael B. ;

Stafford, Jeffrey A. ;

Kaldor, Stephen W. ;

Kassel, Daniel B. ;

Navre, Marc ;

Shi, Lihong ;

Skene, Robert J. ;

Asakawa, Tomoko ;

Takeuchi, Koji ;

Xu, Rongda ;

Webb, David R. ;

Gwaltney, Stephen L., II .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (10) :2297-2300

[6] T3P:: A convenient and useful reagent in organic synthesis [J].

Garcia, Ariel L. Llanes .

SYNLETT, 2007, (08) :1328-1329

[7] New observations on peptide bond formation using CDMT [J].

Garrett, CE ;

Jiang, XL ;

Prasad, K ;

Repic, O .

TETRAHEDRON LETTERS, 2002, 43 (23) :4161-4165

[8]

HAFFNER CD, 2003, Patent No. 2003002531

[9] Preparation of an amino acid intermediate for the dipeptidyl peptidase IV inhibitor, saxagliptin, using a modified phenylalanine dehydrogenase [J].

Hanson, Ronald L. ;

Goldberg, Steven L. ;

Brzozowski, David B. ;

Tully, Thomas P. ;

Cazzulino, Dana ;

Parker, William L. ;

Lyngberg, Olav K. ;

Vu, Truc C. ;

Wong, Michael K. ;

Patel, Ramesh N. .

ADVANCED SYNTHESIS & CATALYSIS, 2007, 349 (8-9) :1369-1378

[10] Stereoselective synthesis of cis-1,3-disubstituted cyclobutyl kinase inhibitors [J].

Helal, CJ ;

Kang, ZJ ;

Lucas, JC ;

Bohall, BR .

ORGANIC LETTERS, 2004, 6 (11) :1853-1856

← 1 2 →