Synthesis of novel 2,4-disubstituted 3H-pyrido[3,2-e][1,4]diazepin-5-ones and 2,4-disubstituted 3H-pyrido[2,3-e][1,4]diazepin-5-ones derivatives via regioselective thionation and nucleophilic substitutions reactions

An efficient synthesis leading to novel 2,4-disubstituted 3H-pyrido[3,2-e][1,4]diazepin-5-ones and 2,4-disubstituted 3H-pyrido[2,3-e][1,4]diazepin-5-ones derivatives is presented, using the condensation of ethyl 2-(benzylamino)acetate or ethyl 2-(4-methoxybenzylamino)acetate with 1H-pyrido[3,2-d][1,3]oxazine-2,4-diones and 1H-pyrido[2,3-d][1,3]oxazine-2,4-diones. This synthesis gives 4-substituted 3-hydro-1H-pyrido[3,2-e][1,4]diazepine-2,5-diones and 4-benzyl-3,4-dihydro-1H-pyrido[2,3-e][1,4]diazepine-2,5-diones in good yields. Finally, after a regioselective thionation and nucleophilic substitutions reactions, various bis-functionalized 1,4-diazepines were easily obtained in excellent yields. These results open an access way to a library of novel bis-functionalized pyrido-1,4-diazepines.