Practical Synthesis of a Stable Precursor for Positron Emission Tomography Imaging Agent ¹⁸F-GTP1

18 F-GTP1 is a deuterated small molecule positron emission tomography (PET) imaging agent used to visualize tau tangles in Alzheimer’s disease patients. The first-generation synthesis of 18 F-GTP1 ’s nonradiolabeled alkyl tosylate precursor was plagued by low-yielding steps, inefficient chromatographic purifications, and variable product quality. Due to these limitations, a more robust second-generation route was developed and successfully executed on kilogram scale. A reduction with LiAlD 4 incorporated geminal deuterium atoms, while an efficient amidation reaction accessed the key acrylamide coupling partner. Moreover, the tricyclic imidazo[1,2- a ]pyrimidine core was assembled via a novel, convergent, and highly selective phosphoramidate-directed annulation. The improved synthesis eliminated all chromatography en route to a high-yielding and reproducible acid-promoted tosylation as the final step.