Stereoselective synthesis of a KRASG12C inhibitor with quinoline-piperazine scaffold

Abstract

We developed a novel synthetic route for the KRASG12C inhibitor, focusing on the efficient construc-tion of its central quinoline scaffold. The method for constructing the quinoline scaffold offers several ad-vantages: it 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 the gentle hydrolysis of the phenyl esters with metha-nol and potassium car-bonate, which greatly re-duces the occurrence of side reactions. In addition, the stereoisomers were successfully separated by silica gel column chroma-tography using a 30:1 DCM/triethylamine solvent system.