New Page 1

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 Petrič^a*
^aFaculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia. E-Mail: andrej.petric@fkkt.uni-lj.si
^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

Abstract
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