A concise and efficient synthesis of flumazenil and its precursor for radiolabeling with fluorine-18

Presently there is a strong interest in developing radioligands for in vivo imaging the GABAA-Bz site with positron emission tomography (PET). Flumazenil (1), a high-affinity GABAA-Bz site inverse agonist, is amenable for 11C and 18F-labeling. The current methods for synthesis of 1 and its precursor for 18F-labeling are not ideal and restrict structure–activity relationship (SAR) development. Herein we present a novel and less troublesome synthesis of 1 and its cognates to aid in the development of improved radioligands for PET imaging of GABAA-Bz site.