Synthesis and characterization of new heterocycles related to aryl[e][1,3]diazepinediones. rearrangement to 2,4-diamino-1,3,5-triazine derivatives†
Novel non-planar heterocycles make a great contribution to drug design and medicinal chemistry. Fused aryl[e][1,3]diazepinediones are a less investigated and appealing class of compounds. Herein, we designed 5 types of polynitrogen containing compounds based on 3-aminobenzo[e][1,3]diazepine-1,5-dione and undescribed 3-aminopyrido[3,4-e][1,3]diazepine-1,5-dione, 7-aminopyrido[2,3-e][1,3]diazepine-5,9-dione and 7-aminopyrazino[2,3-e][1,3]diazepine-5,9-dione. The synthesis, characterization, chemical properties, and X-ray structures are presented. Stability studies led to the identification of a novel rearrangement of 2-guanidino-benzo[e][1,3]diazepine-4,7-dione to 2,4-diamino-6-phenyl-1,3,5-triazines by hydrolytic ring-opening followed by cyclocondensation. This reactivity has been used to efficiently access, after optimization, an “activated” 2,2,2-trifluoroester, which was successively transformed into variously functionalized derivatives by hydrolysis, transesterification or amide formation. These latter structures present high potential as precursors of drug-like molecules.