Facile Synthesis of 7-Alkyl-1,2,3,4-tetrahydro-[1,8]-naphthyridines as Arginine Mimetics Using a Horner–Wadsworth–Emmons Based Approach

Abstract

<jats:p>Integrin inhibitors based on the tripeptide sequence Arg-Gly-Asp (RGD) are potential therapeutics for the treatment of idiopathic pulmonary fibrosis (IPF). Herein, we describe an expeditious three-step synthetic sequence of Horner–Wadsworth–Emmons olefination, diimide reduction and global deprotection to synthesise cores for these compounds in high yields (63–83% over 3 steps) with no need for chromatography. Key to this transformation is the phosphoramidate protecting group, which is stable to metalation steps.</jats:p>