June 3, 2011
8:00 am Morning Coffee
8:30 am Chairperson’s Remarks
Robert Hughes, Ph.D., Scientist II, Chemical Development, Vertex
» KEYNOTE PRESENTATION:
8:35 Formation of C-C Bonds via Catalytic Hydrogenation and Transfer Hydrogenation
 Michael J. Krische, Ph.D., Chair, Department of Chemistry and Biochemistry and Director, Center for Green Chemistry and Catalysis, University of Texas at Austin
Under hydrogenation conditions employing cationic rhodium and iridium catalysts, diverse π-unsaturated reactants engage in reductive C-C coupling to carbonyl compounds and imines, offering a byproduct-free alternative to stoichiometric organometallic reagents in a range of classical C=X (X = O, NR) addition processes. This concept is extended further by “C-C bond forming transfer hydrogenations”. Here, using ruthenium or iridium catalysts, alcohols serve dually as hydrogen donors and aldehyde precursors, enabling carbonyl addition directly from the alcohol oxidation level in the absence of stoichiometric byproducts. These processes represent the first C-C bond forming hydrogenations beyond hydroformylation.
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9:15 Application of QbD principles and PAT in Drug Development
Ambarish Singh, Ph.D., Associate Director, CMC, Bristol-Myers Squibb
An overarching goal of pharmaceutical development is to design & develop synthetic routes and formulations for drug candidates that meet the safety, efficacy and commercial requirements. The application of QbD principles and PAT (including other productivity enhancing tools) can help scientists create process knowledge and develop appropriate controls more efficiently. This presentation will discuss key concepts of QbD and PAT and application of these concepts in the development of manufacturing processes.
9:45 Ensuring PAT Methods are Fit-for-Purpose
Justin Pritchard, Scientist I, Analytical Development, Vertex Pharmaceuticals
Ensuring PAT methods are fit-for-purpose benefits from a different approach to examining method capability than the traditional approach to analytical method validation. The gauge R&R approach used by other manufacturing industries enables a more applicable analysis of method capability and method variability. Pharmaceutical PAT methods are considered with respect to measurement system variability, process variability, and optimizing the measurement system to ensure capability for observing the critical attribute.
10:15 Report-out of Breakout Discussion Groups from Day 1
Moderators of Breakout Topics (Leadbeater, Makowski, Srirangam,Truppo)
10:30 Coffee Break with Exhibit and Poster Viewing
11:00 AProcess Development of PD 348292
Bob Dugger, Ph.D., Research Fellow, Chemical Research and Development, Pfizer Global R&D
11:30 Panel Discussion: QbD and Genotoxicity
Moderator: Neal Anderson, Ph.D., Anderson’s Process Solutions
Panelists:
Bob Dugger, Ph.D., Research Fellow, Chemical Research and Development, Pfizer Global R&D
Ravi S. Harapanhalli, Ph.D., Principal Consultant and Late Stage Services Lead, PAREXEL Consulting
Michelle Kenyon, Principal Scientist, Pfizer Global Research and DevelopmentDrug Safety R&D, Genetic Toxicology
Ambarish Singh, Ph.D., Associate Director, CMC, Bristol-Myers Squibb
- Applying current ICH genotoxicity guidelines
- Best approaches in presenting data to the FDA on issues of genotoxicity
- How implementing QbD affects genotoxicity
testing requirements
12:00 pm Lunch on Your Own
1:55 Chairperson’s Remarks
Jay Srirangam, Ph.D., Associate Research Fellow, La Jolla Laboratories, Pfizer Global R&D
2:00 Biocatalytic Manufacturing Routes to Sitagliptin and Odanacatib
Matthew Truppo, Ph.D., Senior Scientist, Process Chemistry, Merck
This talk will cover the development of the transamination route to Sitagliptin (Januvia) and flow/chemistry - continuous processing in the biocatalytic manufacture of odanacatib (investigational drug for osteoporosis).
2:30 Process Development of the selective VEGH inhibitor Axitinib (AG-
013736)
Jay Srirangam, Ph.D., Associate Research Fellow, La Jolla Laboratories, Pfizer Global R&D
Axitinib is a VEGF inhibitor currently in advanced clinical trials for cancer. The original synthesis of this compound involved 11 steps from 6-nitroindazole. Efforts to overcome the bottlenecks and development of a scalable process for exploratory development will be discussed. This will be followed by process research work on the development of a three step process utilizing efficient Pd cross couplings.
3:00 Selective and Efficient Hydrogenation of Pharmaceutical Intermediates with Trickle-“Shallow”-Bed Flow Reactors
Teresa Makowski, Senior Scientist, Chemical Technology Group, Chemical Research & Development, Pfizer Worldwide R&D
Trickle bed reactors are widely used for efficient large scale multiphase reactions in the petrochemical industry, but they have not been widely used in the fine chemical and pharmaceutical industries. We have found that shallow beds of fine catalyst particles can be used in trickle bed reactors for the hydrogenation of substituted pyridines, nitro compounds, and other functional groups with enhanced diastereoselectivity, purity control, and catalyst activity relative to the corresponding batch hydrogenations.
3:30 Networking Refreshment Break with Exhibit and Poster Viewing
4:00 A Practical Enantioselective Synthesis of a Novel Peptide Deformylase Inhibitor
Mahavir Prashad, Ph.D., Head of Chemical Development Unit US. Novartis Pharmaceuticals Corporation
4:30 Scale-up of Microwave-assisted Chemistry: Batch Approaches and Going with the Flow
Nicholas E. Leadbeater, Ph.D., Professor, Department of Chemistry, University of Connecticut
Microwave heating seems useful for preparation of the first gram or so of our compounds, but is it scalable?” This is a question that is frequently asked and it certainly has some validity. For microwave heating to be a technology that is useful from an industrial standpoint, the methodologies developed on a small-scale need to be scalable to make more significant quantities of material. Using examples from our laboratory, this presentation will address this question. Both microwave heating in batch and conventional heating in continuous-flow mode will be showcased.
5:00 End of Conference