[1] Cao Meng, Zhao Hucheng, Hu Bing, Ji Min, et al. Optimization of cross-coupling reaction for synthesisof antitumor drug vismodegib [J]. Journal of Southeast University (English Edition), 2014, 30 (1): 72-76. [doi:10.3969/j.issn.1003-7985.2014.01.014]

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Optimization of cross-coupling reaction for synthesisof antitumor drug vismodegib()

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Journal of Southeast University (English Edition)[ISSN:1003-7985/CN:32-1325/N]

Volumn:

30

Issue:

2014 1

Page:

72-76

Research Field:

Chemistry and Chemical Engineering

Publishing date:

2014-03-31

Info

Title:

Optimization of cross-coupling reaction for synthesisof antitumor drug vismodegib

Author(s):

Cao Meng;  Zhao Hucheng;  Hu Bing;  Ji Min

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

Keywords:

vismodegib;  synthesis;  cross-coupling;  optimization

PACS:

TQ463

DOI:

10.3969/j.issn.1003-7985.2014.01.014

Abstract:

In order to improve the yield and reduce the cost in the synthesis of antitumor drug vismodegib, the key intermediates are prepared and the Negishi reaction step is examined. The effects of different molar ratios of reactants, dosages of catalyst and time for refluxing are investigated by using single factor tests. The results demonstrate that, when the molar ratios of 2-bromopyridine, 2-chloro-N-(4-chloro-3-iodophenyl)-4-(methylsulfonyl)benzamide, zinc chloride, n-butyllithium and tetrakis(triphenyl phosphine)palladium are changed to 1.0∶0.5∶1.5∶1.1∶0.05 and the mixture is refluxed for 24 h, the production yield is improved to 72%. This reaction condition significantly enhances the synthetic efficiency, avoids consuming excessive raw materials/catalysts, and, meanwhile, prevents a prolonged reaction time. The optimization of the proportion of reactants and the heating time is proved to be important for the efficiency and economy in cross-coupling reaction to synthesize vismodegib.

References:

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Memo

Memo:

Biographies: Cao Meng(1983—), male, doctor; Ji Min(corresponding author), female, doctor, professor, jimin@seu.edu.cn.
Foundation items: The National Basic Research Program of China(973 Program)(No.2011CB933503), China Postdoctoral Science Foundation(No.2013M541592).
Citation: Cao Meng, Zhao Hucheng, Hu Bing, et al. Optimization of cross-coupling reaction for synthesis of antitumor drug vismodegib[J].Journal of Southeast University(English Edition), 2014, 30(1):72-76.[doi:10.3969/j.issn.1003-7985.2014.01.014]

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