Development of a continuous flow synthesis of FGIN-1-27 enabled by in-line 19F NMR analyses and optimization algorithms

Abstract

A straightforward continuous flow synthesis of FGIN-1-27, a compound with potent anxiolytic effects, is described from inexpensive and commercially available starting materials. The four-step synthesis includes the direct C–H arylation of an indole with an arenediazonium salt. The continuous flow route was developed thanks to the use of enabling technologies such as real-time in-line benchtop ¹⁹F NMR analysis and an optimization algorithm assisting the decision-making process. These enabling technologies increase the process safety and minimize the number of experiments required in optimization campaigns.