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

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 [18F]fluoroanilines for evaluation as EGFR targeting agents with PET. By a cyclization reaction, 2‐[18F]fluoroaniline was reacted with N′‐(2‐cyano‐4‐nitrophenyl)‐N,N‐dimethylimidoformamide to produce 6‐nitro‐4‐(2‐[18F]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‐[18F]fluoroanilino)quinazoline in 8.5% decay‐corrected radiochemical yield, from starting fluoride, in less than 2 h.