Synthesis of Some Pyrimido (4,5-d) pyrimidines as Potential Purine Antagonists

Abstract

Synthesis of a number of pyrimido(4,5-d)pyrimidines by four independent routes is reported. The first involves the cyclization of substituted 4-aminopyrimidine-5-thiocarboxamides by the action of ethyl orthoformate and acetic anhydride to give a variety of 4-thiopyrimido(4,S-d)pyrimidines. The second involves the cyclization of 4-amino-S-cyanopyrimidines with formamide to .give 4-aminopyrimido(4,5-d)pyrimidines. The third and the fourth methods involve the catalytic reduction of 2-substituted-4-amino-S-cyanopyrimidines to' the corresponding 4-amino-5-aniinomethylpyrimidinesfollowed by (a) reaction with sodium dithioformate and subsequent cyclization of the S-thioformamidomethyl derivatives to 3,4-dihydropyrimido(4,5-d)pyrimidines and (b) condensation with carbon disulphide and subsequent ring closure of the, inner salt of 4-amino-S-pyrimidylmethyl dithiocarbamic acid to 3,4-dihydropyrimido(4,5-d)pyrimidine-2-(1,H)-thiones.