Heterocyclic studies. Part 44. Novel tricyclic compounds containing the pyrimido[5,4-d]-1,2,3-triazine system

Abstract

Treatment of methyl 8-amino-5-chloro-2,3-dihydroimidazo[1,2,-c]pyrimidine-7-carboxylate with suitable amines and then nitrous acid gave derivatives (4) of the novel heterocyclic system imidazo[1′,2′:1,6]pyrimido[5,4-d][1,2,3]triazine. The same heterocyclic system in the form of an 8-oxide derivative (5) resulted from nitrous acid treatment of 8-amino-5-methylamino-7-methyl-2,3-dihydroimidazo[1,2-c]pyrimidine hydrochloride. In a similar way nitrous acid treatment of suitable imidazo- and pyrimido-[1,2-a]pyrimidine hydrochlorides (6; n= 1 or 2) yielded examples of the new heterocyclic systems imidazo- and pyrimido-[2′1′:2,3]pyrimido[5,4-d][1,2,3]triazine (7; n= 1 or 2).

The synthesis of some triazolo-[4,3-a]- and -[1,5-a]-pyrimidines is described and one of these was converted into the 5-morpholino-8-oxide derivative of the novel [1,2,4]triazolo[3′,4′:2,3]pyrimido-[5,4-d][1,2,3]triazine system, compound (14). Acylation of 4-hydrazino-6,8-bisdimethylamino-pyrimido[5,4-d]-1,2,3-triazine (15; R¹= R²= NMe₂, R³= NHNH₂) and cyclisation of the products gave derivatives of the new pyrimido[4,5-e]-1,2,4-triazolo[4,3-c][1,2,3]triazine system (16; R = H, Me, Et, CHCl₂, or NH₂). However, the benzoylhydrazino compound failed to cyclise in polyphosphoric acid and gave, instead, an oxadiazolyl pyrimidine (18; Scheme 2). The hydrazino compound (15; R¹= R²= NMe₂, R³= NHNH₂) gave a pyrimidotetrazolotriazine (22) on treatment with nitrous acid, and a novel pyrimido[4,5-e][1,2,4]triazino[4,3-c][1,2,3]triazine (23) on treatment with pyruvic acid.