Complex chemicals (drugs, chemical probes, diagnostics) are prepared by synthetic routes involving multiple steps. The advent of powerful computation systems and the inherent creativity of synthetic chemists with access to established chemical data results in many plausible strategies to prepare a desired compound; however, we are still unable to predict the success or failure of a particular synthetic route. At present, significant effort is needed to explore planned synthetic strategies, and this may require years of research that may not result in high yields of target compounds. This additional effort as applied to new medicines can cost pharmaceutical companies 5 – 20+ years and tens to hundreds of millions of dollars to screen for economically viable syntheses of drug compounds. Additional time is often needed to optimize processes to reduce production costs. We present, SynJet, a platform combining a modified thermal inkjet technology with parallelized sample handling to facilitate high-throughput chemical reaction screening and optimization (RSO) using common laboratory analytics. The process is streamlined for reaction parallelization and intelligent grouping of mixtures using Design of Experiment (DoE) guidance. This system uses a rapid chemical dispenser, individualized reaction vials, parallelized heating, and robotic manipulation to transport the samples from dispenser to reactor and to the analytics. We will present results demonstrating the screening of a nucleophilic aromatic substitution reaction of 24 amines (both primary and secondary) with 48 aryl halides. The system has also been used to optimize a two-step synthesis reaction in hours versus the weeks required by a typical professional chemist using traditional methods. The information generated by SynJet is designed to provide high-throughput chemical reaction information that reports both positive and negative results; the latter provide critical information for machine learning that is generally unreported in the literature. With SynJet, the failures are also illuminated with the fitting algorithm. This allows the researcher to identify the optimal pathway for a synthetic route, interpret why an experiment may not work, and better understand fundamental chemical principles for reaction synthesis.

SynJet: A novel chemical dispensing platform for high throughput reaction screening and optimization

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.