ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

A facile synthetic route for antineoplastic drug GDC-0449

Meng Cao, Hua-You Hu, Hu-Cheng Zhao, Xi-Quan Zhang, Hong-Mei Gu, Ling Yang, Jin Cai, Peng Wang, Bing Hu, and Min Ji

School of Biological Science & Medical Engineering, Southeast University, Nanjing, 210096, China

E-mail: jimin@seu.edu.cn

Abstract: In the current study a facile synthetic route for preparing antineoplastic drug GDC-0449 is investigated. Starting with pyridine-1-oxide and 1-iodo-3-nitrobenzene, the intermediate product 2-(2-chloro-5-nitrophenyl) pyridine was prepared by cross-coupling, deoxidation and halogenation. The final compound was then synthesised by reduction of the nitro group followed by amidation. This synthetic route avoids the use of unstable organometallic or organic boride compounds; it employs relatively inexpensive and bench-stable reagents, involves readily controllable reaction conditions, and achieves a relatively high yield.

Keywords: GDC-0449 – pyridine 1-oxide – cross-coupling – halogenation – synthesis

Full paper is available at www.springerlink.com.

DOI: 10.2478/s11696-014-0581-3

Chemical Papers 68 (10) 1408–1414 (2014)