Synthesis of 6‐acrylamido‐4‐(2‐[¹⁸F]fluoroanilino)quinazoline: a prospective irreversible EGFR binding probe

Abstract

Abstract Acrylamido‐quinazolines substituted at the 6‐position bind irreversibly to the intracellular ATP binding domain of the epidermal growth factor receptor (EGFR). A general route was developed for preparing 6‐substituted‐4‐anilinoquinazolines from [ 18 F]fluoroanilines for evaluation as EGFR targeting agents with PET. By a cyclization reaction, 2‐[ 18 F]fluoroaniline was reacted with N′ ‐(2‐cyano‐4‐nitrophenyl)‐ N , N ‐dimethylimidoformamide to produce 6‐nitro‐4‐(2‐[ 18 F]fluoroanilino)quinazoline in 27.5% decay‐corrected radiochemical yield. Acid mediated tin chloride reduction of the nitro group was achieved in 5 min (80% conversion) and subsequent acylation with acrylic acid gave 6‐acrylamido‐4‐(2‐[ 18 F]fluoroanilino)quinazoline in 8.5% decay‐corrected radiochemical yield, from starting fluoride, in less than 2 h. Copyright © 2005 John Wiley & Sons, Ltd.