A novel method for the synthesis of imidazo[5,1-f][1,2,4]triazin-4(3H)-ones.
[reaction: see text] Imidazo[5,1-f][1,2,4]triazinones, as isosteres of purine, are of interest for pharmaceutical research. The syntheses reported in the literature generally require several steps. We report a novel method to access a broad range of diversely substituted derivatives. The key step is the electrophilic N-amination of 3H-imidazoles containing a 4-carbonyl group. Several different substituted imidazoles have been N-aminated in this manner. The resulting N-aminoimidazoles were cyclized under different conditions to the corresponding imidazotriazinones, which allowed for additional diversification. This novel method was applied in a formal synthesis of vardenafil, a well-known representative of this class of compounds. Furthermore, we report the first synthesis of a 7-aryl-imidazotriazinone via bromination of an unsubstituted imidazotriazinone followed by a Suzuki coupling.
Heim-Riether
Alexander
A
Lexicon Pharmaceuticals, 350 Carter Road, Princeton, New Jersey 08540, USA. aheim@lexpharma.com
Healy
Jason
J
D007093:Imidazoles / Q000138:chemical synthesis*; D010726:Phosphodiesterase Inhibitors / Q000138:chemical synthesis*; D010879:Piperazines / Q000138:chemical synthesis*; D013450:Sulfones / Q000138:chemical synthesis; D014227:Triazines / Q000138:chemical synthesis; D000069058:Vardenafil Dihydrochloride
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D000069058:Vardenafil Dihydrochloride