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[l,2-c] pyrimidine-7-carboxylate with suitable amines and then nitrous acid gave derivatives (4) of the novel heterocyclic system imidazo[l',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-2,3dihydroimidazo[l,2-c] pyrimidine hydrochloride. In a similar way nitrous acid treatment of suitable imidazo-and pyrimido-[I ,2-alpyrimidine 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-[5,4-4 [1,2,3]triazine system, compound (1 4). Acylation of 4hydrazino-6,8-bisdimethylaminopyrimido[5,4-4-1,2,3-triazine (15; R1 = R2 = NMe,, R3 = NHNH,) and cyclisation of the productsgave derivatives of the new pyrimido[4,5-e] -1,2,4-triazoIo[4,3-c] [1,2,3]triazine system (1 6; R = H, Me, Et, CHCI,, or NH,). 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 = NMe,, R3 = NHNH,) gave a pyrimidotetrazolotriazine (22) on treatment with nitrous acid, and a novel pyrimido[4,5-e] [I ,2,4] triazino[4,3-c] [1,2,3] triazine (23) on treatment with pyruvic acid.An earlier paper in this series described the synthesis of some pyrimido [5,4-d]-1,2,3-triazines and their 3-oxides which were of interest as potential pharmaceuticals. Two new heterocyclic systems, imidazo-and pyrimido-[ 1,2-c]pyrimido[4,5-e][ 1,2,3]triazine were also described. By an unfortunate oversight the earliest example of one of these systems, which was prepared by M. B a k a ~o l i , ~ co-author of this paper, was omitted. The

Synthesis of a Novel Heterocyclic System: Oxazolo[3,2-c]pyrimidine

“…2,4-dichloro-5-nitro-6-methylpyrimidine was first synthesized. 5 This compound was condensed with one equivalent mole of sodium propargyl oxide (Scheme 1). The spectroscopic data ( 1 HNMR and mass spectrum) showed that only one chloro group has been replaced affording either 2-propargyloxypyrimidine 2 or 4-propargyloxypyrimidine 3.…”