Triazines and related products. Part IX. Potential irreversible dihydrofolate reductase inhibitors: 2,4-Diamino-s-triazines with a masked covalent labelling group

A series of 1,2,3-benzotriazin-4(3H)-ones carrying 3-(4,6-diamino-s- triazin-2-ylphenyl) substituents has been prepared by diazotisation of appropriately substituted o-aminobenzamides, or by cyclisation of o-methoxycarbonyl-phenyltriazenes in ethanol containing 2% piperidine. Cyclisation of 1-p-(4,6-diamino-s-triazin-2-yl)phenyl-3-o-cyanophenyltriazene in ethanol-piperidine affords 3-p-(4,6-diamino-s-triazin-2-yl)phenyl-3,4-dihydro- 4-imino-1,2,3-benzotriazine, which in 2N-hydrochloric acid rearranges to the isomeric substituted 4-anilino-1,2,3-benzotriazine. 4-p-Cyanoanilino-1,2,3- benzotriazine decomposes in alcohols containing 1% potassium hydroxide to give ethers; the scope of this reaction has been investigated.