A Practical Synthesis of Highly Functionalized Fused 1,6-Dihydroimidazo-[1,2-a]imidazole-2,5-diones, Key Intermediates for LFA-1 Inhibitors

An alternative and chromatography-free approach for synthesis of a new class of LFA-1 inhibitors was developed. A key feature of this process involved a transformation of thioureas 14 to acyclic guanidine derivatives 9 followed by intramolecular cyclization to highly functionalized bicyclic guanidines 1, that were subsequently converted to 1H-imidazo[1,2-a]imidazol-2-one LFA-1 inhibitors.