| Contents |
1. Copper-catalyzed coupling for a Green process / David J. Ager and Johannes G. de Vries -- 2. Experiences with Negishi couplings on technical scale in early development / Murat Acemoglu, Markus Baenziger, Christoph M. Krell and Wolfgang Marterer -- 3. Developing palladium-catalyzed arylations of carbonyl-activated C-H bonds / Carl A. Busacca and Chris H. Senanayake -- 4. Development of a practical synthesis of naphthyridone p38 MAP kinase inhibitor MK-0913 / John Y.L. Chung -- 5. Practical synthesis of a cathepsin S inhibitor / Xiaohu Deng, Neelakandha S. Mani and Jimmy Liang -- 6. C-N coupling chemistry as a means to achieve a complicated molecular architecture: the AR-A2 case study / Hans-Jürgen Federsel, Martin Hedberg, Fredrik R. Qvarnström and Wei Tian -- 7. Process development and scale-up of PF-03941275, a novel antibiotic / Kevin E. Henegar and Timothy A. Johnson -- 8. Development of a practical Negishi coupling process for the manufacturing of BILB 1941, an HCV polymerase inhibitor / Bruce Z. Lu, Guishen Li, Frank Roschangar, Azad Hossain, Rolf Herter, Vittorio Farina, and Chris H. Henanayake -- 9. Application of a rhodium-catalyzed, asymmetric 1,4-addition to the kilogram-scale manufacture of a pharmaceutical intermediate / Alexandra Parker -- 10. Copper-catalyzed C-N coupling on large scale: an industrial case study / Arianna Ribecai and Paolo Stabile -- 11. Development of a highly efficient regio- and stereoselective Heck reaction for the large-scale manufacture / Per Ryberg -- 12. Commercial development of axitinib (AG-013736): optimization of a convergent pd-catalyzed coupling assembly and solid form challenges / Robert A. Singer -- 13. Large-scale Sonogashira coupling for the synthesis of an mGluR5 negative allosteric modulator / Jeffrey B. Sperry, Roger M. Farr, Mousumi Ghosh and Karen Sutherland -- 14. Palladium-catalyzed bisallylationof erythromycin derivatives / Xiaowen Peng, Guoqiang Wang, Datong Tang -- 15. Route selection and process development for the vanilloid receptor-1 antagonist AMG / Oliver R. Thiel and Jason S. Tedrow -- 16. Transition metal-catalyzed coupling reactions in the synthesis of taranabant: from inception to pilot implementation / Debra J. Wallace -- 17. Ring-closing metathesis in the large-scale synthesis of SB-462795 / Huan Wang -- 18. Development of Migita couplings for the manufacture of a 5-lipoxygenase inhibitor / Weiling Cai, Brian Chekal, David Damon, Danny LaFrance, Kyle Leeman, Carlos Mojica, Andrew Palm, Michael St. Pierre, Janice Sieser, Karen Sutherland, Rajappa Vaidyanathan, John Van Alsten, Brian Vanderplas, Carrie Wager, Gerald Weisenburger, Greg Withbroe and Shu Yu -- 19. Preparation of 4-allylisoindoline via a Kumada coupling with allylmagnesium chloride / Michael J. Zacuto -- 20. Microwave heating and continuous-flow processing as tools for metal-catalyzed couplings: palladium-catalyzed Suzuki-Miyaura, Heck and alkoxycarbonylation reactions / Nicholas E. Leadbeater -- 21. Applying the hydrophobic effect to transition metal-catalyzed couplings in water at room temperature / Bruce H. Lipshutz -- 22. Large-scale applications of transition metal removal techniques in the manufacture of pharmaaceuticals / Javier Magano. |
| Summary |
Transition metal-catalyzed coupling reactions have a rich history that led to the awarding of the 2010 Nobel Prize in Chemistry to Professors Suzuki, Heck, and Negishi for their pioneering contributions to the field. The coming of age of this active area of research is showcased in this book through case studies in which process chemists from the pharmaceutical industry share their experiences developing transition metal-catalyzed couplings for the large-scale manufacture of active pharmaceutical ingredients.Authors from Pfizer, Merck, Boehringer-Ingelheim, Novartis, Amgen, GSK, AstraZeneca, and other companies describe the evolution of robust coupling processes from inception through early and late development, including commercial routes where applicable. The book covers a wide range of coupling transformations while capturing the lessons learned from each process. Every case study details at least one transition metal-catalyzed coupling while elaborating on issues such as design of experiments, scalability and throughput, product purification, process safety, and waste management. The important issue of metal removal and the different technologies available to accomplish this goal are also addressed. Finally, a section covers novel technologies for cross-coupling with high potential for future applications on a large scale, such as microwave and flow chemistry as well as green cross-couplings performed in water. |
