Synthesis of pteridine derivatives related to folic acid and methanopterin from pyrazine-2,3-dicarbonitrile

Article abstract of DOI:10.1002/jhet.5570340341

Pteridine derivatives related to folic acid and methanopterin were synthesized by two methods. The first synthesis is initiated by the radical substitution of 5-methylpyrazine-2,3-dicarbonitrile (3) with the (N-acyl- anilino)alkyl radical to give 6-methyl-5-(N-acylanilino)alkylpyrazine-2,3- dicarbonitrile (9) and was followed by the substitution of the 2-carbonitrile with methylamine and further conversion to 1 -methyl-2-amino-6-(N- acylanilino)-alkyl-7-methylpteridin-4(1H)-imine 11 by the action of guanidine. The second method is initiated by radical hydroxymethylation of 5- methylpyrazine-2,3-dicarbonitrile (3) to give 5-hydroxymethyl-6- methylpyrazine-2,3-dicarbonitrile (15), followed by oxidation of the hydroxymethyl group, N-phenylimination, and the substitution of the 2- carbonitrile with methylamine to give 6-methyl-2-methyl-amino-5-(N- phenylimino)methenylpyrazine-3-carbonitrile (18). The reduction of the imino group and the final cyclization with guanidine gives 2-amino-6-anilinomethyl- 1,7-dimethylpteridin-4(1H)-imine (20).