An efficient synthesis of (fluoromethyl)pyridylamines for labeling with fluorine-18

We have described a two-step method for the preparation of (fluoromethyl)py ridyl-substituted amines. The sequence involves fluoride ion displacement o f methanesulfonates (mesylates) of 6-chloro-alpha-hydroxy-2- and -3-picolin es, followed by arylation of the amine by chloropicoline. We have called th is sequence fluorination-N-arylation. 1-Phenylpiperazine has been used as a model amine. Two key precursors for this sequence are the mesylates of 6-c hloro-alpha-hydroxy-2- and -3-picolines. The former was synthesized in four steps from 6-chloro-2-picoline in 78% yield and the latter in three Steps from 6-chloronicotinic acid in 53% yield. This fluorination-N-arylation seq uence is sufficiently rapid and efficient for the preparation of a variety of aryl-substituted amine compounds labeled with the short half-life (t(1/2 ) = 110 min) positron-emitting radionuclide fluorine-18.