Efficient Electrochemical N-Alkylation of N-Boc-Protected 4-Aminopyridines: Towards New Biologically Active Compounds

The use of electrogenerated acetonitrile anion allows the alkylation of N -Boc-4-aminopyridine in very high yields, under mild conditions and without by-products. The high reactivity of this base is due to its large tetraethylammonium counterion, which leaves the acetonitrile anion “naked.” The deprotection of the obtained compounds led to high yields in N -alkylated 4-aminopyridines. Nonsymmetrically dialkylated 4-aminopyridines were obtained by subsequent reaction of monoalkylated ones with t -BuOK and alkyl halides, while symmetrically dialkylated 4-aminopyridines were obtained by direct reaction of 4-aminopyridine with an excess of t -BuOK and alkyl halides. Some mono- and dialkyl-4-aminopyridines were selected to evaluate antifungal and antiprotozoal activity; the dialkylated 4-aminopyridines 3ac , 3ae and 3ff showed antifungal towards Cryptococcus neoformans ; whereas 3cc , 3ee and 3ff showed antiprotozoal activity towards Leishmania infantum and Plasmodium falciparum .