Abstract

Flow Enabled Synthesis of Multiresistant Drug Clofazimine

Paul Watts, Postdoc, Nelson Mandela University

Drug resistance to tuberculosis is still one of the significant challenges worldwide. Clofazimine, which belongs to the riminophenazine (anti-biotic) class, is still one of the active drugs that are efficient against drug resistance M. Tuberculosis. Apart from this, it is also a WHO-approved drug for the treatment of leprosy (Hansen's Disease) and, at present, is under phase 2 clinical trial for its activity against the SARS-CoV-2 virus. Owing to its vast importance in clinical research, we have developed a continuous-flow mediated synthesis of clofazimine using readily available p-chloroaniline and 1-fluro-2-nitrobenzene. The target drug molecule was obtained from four consecutive chemical transformations with nominal reaction time and improved purity and yields when compared to the batch process. Moreover, the first two steps were also successfully telescoped under optimized reaction conditions.