Development of an effective palladium removal process for VEGF oncology candidate AG13736 and a simple, efficient screening technique for scavenger reagent identification

被引：56

作者：

Flahive, Erik J. ^{[1
]}

Ewanicki, Brigitte L. ^{[1
]}

Sach, Neal W. ^{[2
]}

O'Neill-Slawecki, Stacy A. ^{[1
]}

Stankovic, Nebojsa S. ^{[1
]}

Yu, Shu ^{[1
]}

Guinness, Steven M. ^{[3
]}

Dunn, Jonathan ^{[4
]}

机构：

[1] Pfizer Global R&D, Chem Res & Dev, San Diego, CA 92121 USA

[2] Pfizer Global R&D, Chem Res & Dev, Groton, CT 06340 USA

[3] Pfizer Global R&D, Chem Res & Dev, Sandwich CT13 9NJ, Kent, England

[4] Pfizer Global R&D, Analyt Res & Dev, San Diego, CA 92121 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2008年 / 12卷 / 04期

关键词：

D O I：

10.1021/op600280g

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

AG13736 (Axitinib), an inhibitor of vascular endothelial growth factor (VEGF) under investigation as an oncology drug, is currently manufactured via a three-step process that utilizes two palladium-mediated cross-couplings. Historically, removal of residual heavy metals from the active pharmaceutical ingredient has been a persistent issue. The development of a much improved process for palladium removal and a useful screening technique developed to rapidly identify the most efficient reagents for this purpose are outlined. The performance of the new endgame process in pilot-plant scale-up is also discussed.

引用

页码：637 / 645

页数：9

共 9 条

[1]

Bien JT, 2004, TOP ORGANOMETAL CHEM, V6, P263

[2] Vascular endothelial growth factor as a target for anticancer therapy [J].

Ferrara, N .

ONCOLOGIST, 2004, 9 :2-10

[3] A high-throughput chelating agents for methodology for screening solution-based efficient palladium removal [J].

Flahive, Erik ;

Ewanicki, Brigitte ;

Yu, Shu ;

Higginson, Paul D. ;

Sach, Neal W. ;

Morao, Inaki .

QSAR & COMBINATORIAL SCIENCE, 2007, 26 (05) :679-685

[4] The art of meeting palladium specifications in active pharmaceutical ingredients produced by Pd-catalyzed reactions [J].

Garrett, CE ;

Prasad, K .

ADVANCED SYNTHESIS & CATALYSIS, 2004, 346 (08) :889-900

[5] A practical synthesis of 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-ethylquinazoline and the art of removing palladium from the products of Pd-catalyzed reactions [J].

Königsberger, K ;

Chen, GP ;

Wu, RR ;

Girgis, MJ ;

Prasad, K ;

Repic, O ;

Blacklock, TJ .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2003, 7 (05) :733-742

[6] Large-scale Negishi coupling as applied to the synthesis of PDE472, an inhibitor of phosphodiesterase type 4D [J].

Manley, PW ;

Acemoglu, M ;

Marterer, W ;

Pachinger, W .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2003, 7 (03) :436-445

[7] Cross-coupling methods for the large-scale preparation of an imidazole-thienopyridine:: Synthesis of [2-(3-methyl-3H-imidazol-4-yl)thieno[3,2-b]pyridin-7-yl]-(2-methyl-1H-indol-5-yl)-amine [J].

Ragan, JA ;

Raggon, JW ;

Hill, PD ;

Jones, BP ;

McDermott, RE ;

Munchhof, MJ ;

Marx, MA ;

Casavant, JM ;

Cooper, BA ;

Doty, JL ;

Lu, Y .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2003, 7 (05) :676-683

[8] A novel methodology for efficient removal of residual palladium from a product of the Suzuki-Miyaura coupling with polymer-supported ethylenediamine derivatives [J].

Urawa, Y ;

Miyazawa, M ;

Ozeki, N ;

Ogura, K .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2003, 7 (02) :191-195

[9] Adsorbent screening for metal impurity removal in pharmaceutical process research [J].

Welch, CJ ;

Albaneze-Walker, J ;

Leonard, WR ;

Biba, M ;

DaSilva, J ;

Henderson, D ;

Laing, B ;

Mathre, DJ ;

Spencer, S ;

Bu, XD ;

Wang, TB .

ORGANIC PROCESS RESEARCH & DEVELOPMENT, 2005, 9 (02) :198-205

← 1 →