(328b) Autonomous Reaction Platform for Continuous Chemical Synthesis

Authors: 
Thomas, D., Massachusetts Institute of Technology
Coley, C. W., Massachusetts Institute of Technology
Rogers, L., Massachusetts Institute of Technology
Jamison, T., Massachusetts Institute of Technology
Jensen, K. F., Massachusetts Institute of Technology
Hart, A. J., Massachusetts Institute of Technology
Schultz, V., Rensselaer Polytechnic Institute
During all stages of the pharmaceutical development, the ability for synthetic chemistry to create and modify new molecules is crucial for library generation, toxicology, and pharmacokinetics optimization; however, the field has struggled with the slow pace of synthetic route planning and synthesis resulting in long project timelines in the development pipeline. Advances in laboratory automation can address this bottleneck by increasing expert chemists productivity when developing new molecules. Automated reaction platforms require the integration of route planning with a library of process units, beyond simple mixing and stirring, capable of carrying out multi-step syntheses, inline reaction monitoring, and easily reconfigurable between molecules.

Our research has focused on the development of a continuous flow chemistry platform capable of multi-step syntheses, and robotic reconfigurability. Our talk will discuss, the integration of a library of flow chemistry modules capable of handling solids, aggressive reagents, inline separations and the intense reaction conditions required for organic synthesis. The system is designed to assemble modules and fluidic connections into a continuous flow process. The assembly of the system is coordinated through a web-based interface which generates reaction recipes and can be connected to a synthetic route planning software. Our platform has been used to rapidly synthesize a variety of active pharmaceutical ingredients (API) and dyes requiring stereoselectivity, site-selectivity, library generation, and convergent synthesis. Through the development of flexible process modules, our integrated robotic platform aims to decrease the time required to synthesizing new molecules while increasing synthetic repeatability and lab-to-lab transferability. Automation of synthetic chemistry can decrease the time for molecule development and allow chemists to focus on pathway refinement, reaction optimization, and process analytics.