A convenient access to new pyrido[4,3-d]pyrimidine, thiazolo[3,4-c] pyrimidine and pyrimido[4,5-d]pyridazine derivatives

Abstract

Several new pyrido[4,3-d]pyrimidine, pyrimido[4,5-d]pyridazine and thiazolo[3,4-c]pyrimidine derivatives were prepared from the versatile, readily accessible ethyl 6-methyl-2-oxo-4-phenyl-1,2,3,4-tetrahydropyrimidine-5- carboxylate. Bromination of the latter compound afforded the corresponding 6-bromomethylpyrimidine derivative. Treatment of the latter with malononitrile or ethyl cyanoacetate afforded the corresponding hexahydrocyclopenta[d] pyrimidine derivatives 4a,b. Reaction of the bromomethylpyrimidine with potassium cyanide followed by treatment with arenediazonium salt afforded the corresponding hydrazone 6 which reacts with hydrazine derivatives to afford the corresponding pyrido[4,3-d]pyrimidine derivatives 8a,b. It reacts also with thiourea, thiosemicarbazide and phenylhydrazine to afford ethyl 3-imino-5-oxo-7-phenyl-3,5,6,7-tetrahydro-1-H-thiazolo[4,3-c] pyrimidine-8-carboxylate (10a), ethyl 3-hydrazono-5-oxo-7-phenyl-3,5,6,7- tetrahydro-1-H-thiazolo[3,4-c]pyrimidine-8-carboxylate (10b) and 4,6-diphenyl-3,4,7,8-tetrahydropyrimido[4,5-d]pyridazine-2,5-(1H,6H)-dione (12), respectively. The antimicrobial activity of selected examples of the synthesized compounds was tested and showed moderate activity. © ARKAT USA, Inc.