Alkylation of [1,2,4]triazolo[1,5-a][1,3,5]triazin-7(3H)-ones

Abstract

The results of pioneering research on the alkylation of fused [1,2,4]triazolo[1,5-a][1,3,5]triazine system are presented, including computational studies of the reaction between 5-dimethylamino[1,2,4]triazolo[1,5-a][1,3,5]triazin-7(3H)-one and bromoethane. The reaction of 5-amino-substituted [1,2,4]triazolo[1,5-a][1,3,5]triazin-7(3H)-ones with allyl bromide, bromoethane, or (2-acetoxyethoxy)methyl bromide occurred selectively with the formation of products due to alkylation at the N-3 nitrogen atom of the heterocyclic system. The removal of acetyl protecting group from 5-amino-substituted {2-[(7-oxo[1,2,4]triazolo[1,5-a][1,3,5]triazin-3(7H)-yl)methoxy]ethyl}acetates gave 5-aza analogs of acyclovir, containing a substituted amino group at position 5 of the heterocyclic 3-[(2-hydroxyethoxy)methyl][1,2,4]-triazolo[1,5-a][1,3,5]triazin-7(3H)-one system.