12. The Discovery of A New Pd/Cu Catalytic System For C[BOND]H Arylation and Its Applications in A Pharmaceutical Process

  1. Peter J. Dunn4,
  2. K. K. (Mimi) Hii5,
  3. Michael J. Krische6 and
  4. Michael T. Williams7
  1. Jinkun Huang1,2,
  2. Xiang Wang1,3 and
  3. Johann Chan1,3

Published Online: 23 MAY 2013

DOI: 10.1002/9781118354520.ch12

Sustainable Catalysis: Challenges and Practices for the Pharmaceutical and Fine Chemical Industries

Sustainable Catalysis: Challenges and Practices for the Pharmaceutical and Fine Chemical Industries

How to Cite

Huang, J., Wang, X. and Chan, J. (2013) The Discovery of A New Pd/Cu Catalytic System For C[BOND]H Arylation and Its Applications in A Pharmaceutical Process, in Sustainable Catalysis: Challenges and Practices for the Pharmaceutical and Fine Chemical Industries (eds P. J. Dunn, K. K. (. Hii, M. J. Krische and M. T. Williams), John Wiley & Sons, Inc., Hoboken, New Jersey. doi: 10.1002/9781118354520.ch12

Editor Information

  1. 4

    Pfizer Green Chemistry Lead, Sandwich, Kent, United Kingdom

  2. 5

    Imperial College London, South Kensington, London, United Kingdom

  3. 6

    University of Texas at Austin, Austin, Texas, United States of America

  4. 7

    CMC Consultant, Deal, Kent, United Kingdom

Author Information

  1. 1

    Chemical Process R&D, Amgen Inc., Thousand Oaks, CA, USA

  2. 2

    Chengdu Suncadia Pharmaceutical Co., Ltd., A Subsidiary of Hengrui Medicine Co., Ltd., China

  3. 3

    Chemical Development, Gilead Sciences, Foster City, CA, USA

Publication History

  1. Published Online: 23 MAY 2013
  2. Published Print: 8 APR 2013

ISBN Information

Print ISBN: 9781118155424

Online ISBN: 9781118354520

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Keywords:

  • Amgen's process;
  • C[BOND]H bond arylation;
  • catalyst design;
  • pharmaceutical intermediate

Summary

C[BOND]H bond arylation methodologies, when applied to process chemistry, often face significant challenges such as high catalyst loading and long reaction times, as well as high reaction temperature that often exceed the boiling point of the reaction solvent at ambient pressure. From a process chemistry standpoint, this lack of practical direct C[BOND]H bond arylation methodologies is unfortunate, as these reactions are not only more atom-economical than the corresponding Suzuki reaction, but can often also provide a shorter and more cost-effective synthetic route to the desired products from commercially available materials. This chapter presents a case study whereby Amgen's process group overcomes the above challenges by developing a new catalyst system that allowed for a scale-up of direct C[BOND]H arylation of azoles under milder conditions to deliver kilogram quantities of a pharmaceutical intermediate. A further discussion of catalyst design and mechanistic insight is also provided.