Total synthesis of LL-Z1640-2 utilizing a late-stage intramolecular Nozaki-Hiyama-Kishi reaction

A total synthesis of LL-Z1640-2 (2), a potent and selective kinase inhibitor, has been completed. The key step of the convergent synthesis utilized a late-stage intramolecular Nozaki-Hiyama-Kishi (NHK) reaction to close the macrocycle at the C6′-C7′ bond.