Rapid access to multi-substituted pyrimido[4,5-b][1,4]diazepine-2,4,6-trione and pyrimido[4,5-b][1,4]diazepine-2,4-dione as novel and versatile scaffolds for drug discovery

A novel pyrimido4,5-b]1,4]diazepine-2,4,6-trione was synthesized with an efficient strategy. Especially, the key intermediate 2,4-dimethoxypyrimido4,5-b]1,4]diazepin-6-one was promoted by one pot tandem reduction-cyclization with Na₂S₂O₄. Subsequently, reduction of lactams 6 with LiAlH₄ afforded a more flexible scaffold of pyrimidodiazepines. The synthetic strategy was versatile since it facilitated the sequential functionalization on the pyrimidodiazepine at three positions. Thus a convenient and effective method for the rapid preparing of multi-substituted pyrimido4,5-b]1,4]diazepines was developed.