Lawrence Berkeley National Laboratory

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 percent decay-corrected radiochemical yield. Acid mediated tin chloride reduction of the nitro group was achieved in 5 min (80 percent conversion) and subsequent acylation with acrylic acid gave 6-acrylamido-4-(2-[18F]fluoroanilino)quinazoline in 8.5 percent decay-corrected radiochemical yield, from starting fluoride, in less than 2 hours.