A practical synthesis of LFA-1 inhibitors utilizing CuCl-promoted intramolecular cyclization of thiohydantoins

摘要

An efficient and chromatography-free approach for synthesis of a new class of LFA-1 inhibitors was developed.A copper~(R)chloride-promoted intramolecular cyclization of thiohydantoins 7a-b serves as a key step to highly functionalized bicyclic guanidines 5a-b,that were subsequently converted to lH-imidazo[l,2-a]imidazol-2-one LFA-1 inhibitors.This process has been successfully implemented in the pilot plant to produce multikilogram quantities of LFA-1 inhibitors such as la-b.