A New Route to Substituted Pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones and Facile Extension to 5,7(6H,8H) Isomers

作者：Turbiak Anjanette J; Showalter H D Hollis^*

来源：Synthesis, 2009, 2009(23): 4022-4026.

DOI：10.1055/s-0029-1217030

• pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones
• pyrimido[5,4-e]-1,2,4-triazine-5,7(6H,8H)-diones
• heterocycles
• hydrazones
• cyclizations

A new route to substituted pyrimido[5,4-e]-1,2,4-triazine-5,7(1H,6H)-diones is outlined. The synthesis proceeds via preformed hydrazone intermediates, which are then condensed with all activated chlorouracil to build up the entire molecular framework, followed by a reductive ring closure to provide the parent series. The route has been extended to the isomeric pyrimido[5,4-e]-1,2,4-triazine-5,7(6H,8H)-dione class via the use of methylhydrazine as hydrazine surrogate, followed by regiospecific alkylation of the N(8)-H pyrimidotriazinediones with a range of alkyl and alkaryl substituents. This new methodology permits the generation of a wide range of compounds with variable substitution at the N(1), C(3), and N(8) positions for a heterocyclic scaffold with demonstrated pharmacological activity.

• 出版日期2009-12-1