Triazines and related products. Part XV. 2,4-Diaminopyrimidines and 2-aminopyrimidin-4(3H)-ones bearing 1,2,3-benzotriazinyl groups as potential dihydrofolic reductase inhibitors

Abstract

Interaction of α-methoxy-o-nitrobenzylidenemalononitrile (8) and guanidinium carbonate afforded 2,4-diamino-6-o-nitrophenylpyrimidine-5-carbonitrile (9) which, on reduction, gave not the expected diamino(aminophenyl)pyrimidine (10) but the triaminopyrimidoquinoline N-oxide (13).

Electrophilic nitration and bromination of 2-amino-6-phenylpyrimidin-4-(3H)-one (7) yielded 5-substituted derivatives: when the 5-position was blocked the substituent entered the para-position of the phenyl group. Rearrangement of 2-nitroamino-6-phenylpyrimidin-4(3H)-one (14) in concentrated sulphuric acid afforded the 2-amino-5-nitropyrimidine (18), whereas attempted photorearrangement gave a complex mixture. Efforts to effect homolytic o-nitrophenylation of uracil with o-nitrophenyl radicals generated from two sources were unsuccessful.

Three pyrimidine derivatives bearing 1,2,3-benzotriazinyl units [(24), (30), and (31)] were prepared by diazotisation of the appropriate o-aminobenzamido-precursors. None of the pyrimidines displayed inhibitory activity against lymphoid leukaemia (L-1210) in mice.