Abstract

Flow Chemistry in Drug Discovery: An Automated Tool to Introduce C(sp3) into Drug Molecules

Jesus Alcazar, Principal Chemist, Janssen Research & Development

Drug discovery process is currently under pressure to get bioactive molecules in the most efficient way. One approach that has been highlighted is the increasing fraction of the C(sp3) atoms in the final target compounds.  However, methodologies to introduce C(sp3) fraction into drug molecules are still challenging for medicinal chemistry and most high throughput chemistry in pharma relies on amide coupling, Suzuki reactions, reductive amination, nucleophilic substitution and sulfonylations. There is a clear need to develop new methodologies for such transformations that can be applicable in a Drug Discovery setting. Continuous flow chemistry has recently emerged as a novel chemical tool that can help synthetic chemists to access forbidden or forgotten chemistries and make them real alternatives for other more classical methods. In this way it enables access to novel chemical space not available by traditional batch procedures. In this presentation we are going to disclose how flow chemistry can be applied to discover new procedures for C(sp3) bond formation to increased Fsp3 in a Drug discovery.  These new methodologies can be transferred to automated platforms for the preparation of libraries and access this new chemical space in a high throughput format.