We developed a novel synthetic route for the KRAS inhibitor, focusing on the efficient construction of its central quinoline scaffold. The method offers several advantages: eliminates the formation of regioselective by-products and avoids the use of high temperatures and nitric acid. The last step of the overall route enables gentle hydrolysis of phenyl esters with methanol and potassium carbonate, which greatly reduces the occurrence of side reactions. In addition, the stereoisomers were successfully separated by silica gel column chromatography.
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