Development and Commercialization of the MiniBlock Synthesizer Family: A Historical Case Study

Abstract

An internal development project at Bristol-Myers Squibb (BMS) led to invention of a family of organic chemistry synthesis blocks for both parallel synthesis in drug discovery and parallel reaction optimization in pharmaceutical development. The internal demand for these synthesis blocks became so great that the original development team was challenged by the burden of ongoing manufacture, support, and supply chain management. As a result, BMS entered into a unique industry partnership with Mettler-Toledo AutoChem (MT), Newark, DE, formerly Bohdan Automation, to commercialize the reactor blocks and extend the product family, now known as the MiniBlock line. This manuscript describes the initial development drivers, the overall technical design, and the ultimate successful commercialization of the MiniBlock synthesis family.

Efficient Screening and Library Generation in Parallel C–C Coupling Reactions Mediated by Organosilica SiliaCat Palladium Catalysts

“…Parallel synthesis over solid reagents or catalysts is now a powerful tool for the synthesis of libraries or collections of new compounds in essentially a single operation using effective tools such as the MiniBlock Synthesizer (MiniBlock is a registered trademark of Mettler-Toledo, Inc.), namely a compact device that enables synthesis via solid- or solution phase under widely controlled environmental conditions inside the reactor (temperature, atmosphere, agitation) as well as purification to be carried out on the same platform . In this report we show that Silia Cat palladium catalysts can be applied to the rapid conversion of widely different substrates in Suzuki, Sonogashira, and Heck coupling reactions run in parallel in the MiniBlock Synthesizer.…”

Emerging Technologies Supporting Chemical Process R&D and Their Increasing Impact on Productivity in the Pharmaceutical Industry

“…A thorough description of the use of the Bohdan market entry, the process development workstation, can be found in a report by Schering researchers . In addition to the commercial implementations, many home-grown systems, such as those in the author's own laboratories and in other's laboratories, were founded on the same basic concepts. Collectively, these workstations aimed to enable a handful of common unit operations: (1) the ability to heat, cool, and stir multiple reactions in parallel, (2) the ability to add liquid reagents and withdraw reaction aliquots automatically, and (3) the ability to analyze samples of the individual reactions by HPLC or GC (either on-line or off-line).…”

Application of Lean Manufacturing Concepts to Drug Discovery: Rapid Analogue Library Synthesis

“…After the initial synthesis request from a program, the first library can usually be delivered in less than two weeks; subsequent libraries are delivered at regular intervals with the synthesis time for each individual library averaging 6−7 days from the initiation of synthesis to submission of final compounds. This was done without making significant changes to our actual synthesis infrastructure: synthesis is done using the MiniBlock or MiniBlock-XT Plus synthesizer, and analysis and purification are done using the customized Shimadzu Discovery-VP chromatography package ,, or, more recently, commercial systems from Waters and Dionex. Other manipulations are done as previously described for larger lead discovery libraries…”