Syntheses of 4-(2-Naphthyl)pyridine Derivatives from DDNP

Primož Škofic,a Cheryl Dambrot,b# Matjaž Koželj,a Amalija Golobič,a Jorge R. Barrio,c and Andrej Petriča*
aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia. E-Mail:
bDepartment of Chemistry and Biomolecular Science, Clarkson University, Potsdam, NY 13699, USA
cDepartment of Molecular and Medical Pharmacology, School of Medicine, University of California at Los Angeles, CA 90095-6948, USA

The ethylidenemalononitrile side-chain in {1-[6-(dimethylamino)-2-naphthyl]­ethylidene}­malononitrile (DDNP) was elaborated into a substituted pyridine ring in a two-step process. In this manner formal derivatives of a molecular probe (1-{6-[(2-fluoroethyl)­(methyl)amino]-2-naphthyl}­ethylidene)malononitrile (FDDNP), which is successfully applied in positron emission tomography to diagnose Alzheimer’s Disease, were prepared. Chloroimidate intermediate in reaction of a nitrile group with HCl in alcoholic solution was trapped in the form of 2-chloro-4-[6-(dimethylamino)-2-naphthyl]nicotinonitrile, thus proving its existence in the Pinner synthesis. The structure of 2-methylamino derivative was also proven by X-ray analysis.

Key words: DDNP, molecular probes, ylidenmalononitriles, Pinner synthesis, X-ray