Development of Scalable Synthesis of RAS Inhibitor’s Indole Building Block via Flow Chemistry

Using flow chemistry, two scalable synthetic routes were developed for the indole building block [5-bromo-3-(3-((tert-butyldiphenylsilyl)oxy)-2,2-dimethylpropyl)-2-iodo-1H-indole], a key intermediate in RAS inhibitors. This approach overcomes limitations of existing literature and patented procedures, which often involve repeated column chromatography purification, low overall yields, the handling of unstable intermediates, challenges in reaction monitoring, and potential safety risks.