First synthesis of piperazine-derived [1,2,4 ]triazolo [1,5 -a ]pyrazine as an adenosine A2a receptor antagonist

Synthesis of piperazine-derived 2-furan-2-yl-[1,2,4]triazolo[1,5-a] pyrazines was achieved using methyl 3-amino-2-pyrazinecarboxylate. Introduction of the piperazine to the pyrazine template was achieved through a pteridin-4-one intermediate (7). Cyclization of the [l,2,4]triazolo[1,5-a]pyrazine ring was accomplished by amination of pyrazine (8) followed by condensation with 2-furaldehyde. Curtius rearrangement installed the amine to afford template (11). As one example of derivatizing 11, 6N-(4-(2,4,6-trifluorobenzyl)piperazin-1-yl)-2-(furan-2-yl)-[1,2,4]triazolo-[1,5-a]pyrazin-8-amine (12) showed moderate adenosine A 2 a receptor binding affinity and selectivity over the A 1 receptor.