Chapter 5. Synthesis of Sitagliptin, the Active Ingredient in Januvia® and Janumet®

  1. Dr. Peter J. Dunn4,5,
  2. Dr. Andrew S. Wells6 and
  3. Dr. Michael T. Williams7
  1. Jaume Balsells1,
  2. Yi Hsiao2,
  3. Karl B. Hansen3,
  4. Feng Xu1,
  5. Norihiro Ikemoto1,
  6. Andrew Clausen3 and
  7. Joseph D. Armstrong III1

Published Online: 19 MAR 2010

DOI: 10.1002/9783527629688.ch5

Green Chemistry in the Pharmaceutical Industry

Green Chemistry in the Pharmaceutical Industry

How to Cite

Balsells, J., Hsiao, Y., Hansen, K. B., Xu, F., Ikemoto, N., Clausen, A. and Armstrong, J. D. (2010) Synthesis of Sitagliptin, the Active Ingredient in Januvia® and Janumet®, in Green Chemistry in the Pharmaceutical Industry (eds P. J. Dunn, A. S. Wells and M. T. Williams), Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany. doi: 10.1002/9783527629688.ch5

Editor Information

  1. 4

    Pfizer Green Chemistry Lead, Ramsgate Road, Sandwich, Kent, CT13 9NJ, United Kingdom

  2. 5

    Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, CT13 9NJ, UK

  3. 6

    Astra Zeneca, Process Research & Development, Bakewell Road, Loughborough, LE11 5RH, United Kingdom

  4. 7

    CMC Consultant, 133, London Road, Deal, Kent, CT14 9TY, United Kingdom

Author Information

  1. 1

    Merck Research Laboratories, Department of Process Research, PO Box 2000, Rahway, NJ 07065, USA

  2. 2

    Bristol Myers Squibb, NB50-358, One Squibb Drive, New Brunswick, NJ 08903, USA

  3. 3

    Amgen Inc., Chemical Process R & D, One Kendall Square, Bldg 1000, Cambridge, MA02139, USA

  1. Dedicated to Edward J. J. Grabowski on the occasion of his 70th birthday.

Publication History

  1. Published Online: 19 MAR 2010
  2. Published Print: 10 MAR 2010

ISBN Information

Print ISBN: 9783527324187

Online ISBN: 9783527629688

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Keywords:

  • sitagliptin;
  • Meldrum's acid;
  • asymmetric hydrogenation

Summary

This chapter contains sections titled:

  • Introduction

  • First-Generation Route

  • Sitagliptin through Diastereoselective Hydrogenation of an Enamine. The PGA Enamine-Ester Route

  • The Triazole Fragment

  • Direct Preparation of β-Keto Amides

  • Second-Generation Chiral Auxiliary Route. The PGA Enamine-amide Route

  • The Asymmetric Hydrogenation Route

  • Purification and Isolation of Sitagliptin (Pharmaceutical Form)

  • The Final Manufacturing Route

  • Acknowledgments

  • References