Bicyclic heterocycles with nitrogen at the ring junction 1. Synthesis and chemistry of imidazo[5,1-f]-1,2,4-triazines

Utilization of 2‐Chloronicotinonitrile in the Syntheses of Novel Fused Bicyclic and Polynuclear Heterocycles of Anticipated Antitumor Activity

“…Thus, refluxing of compound 3 with 2-(1H-benzo[d]imidazol-2-yl)-4-chloro-3-oxobutanenitrile (8) [13,14] On the other hand, compound 1 was allowed to react with salicylic acid in DMF in the presence of sodium carbonate to give 2-(3-cyano-4,6-dimethylpyridin-2-yloxy) benzoic acid 13 (Scheme 3). The structure 13 was elucidated by its correct elemental analysis and spectral data.…”

“…Some newly fused polynuclear heterocycle‐incorporated thienopyridine moieties of anticipated antitumor activity were further synthesized. Thus, refluxing of compound 3 with 2‐(1 H ‐benzo[ d ]imidazol‐2‐yl)‐4‐chloro‐3‐oxobutanenitrile ( 8 ) in DMF containing sodium carbonate afforded benzo[ d ]imidazol‐thieno[2,3‐ b :4,5‐ b ′]dipyridine derivative 10 . Compound 10 was obtained through intramolecular cyclization of the intermediate 9 (Scheme ).…”

“…The completion of reaction and the purity of the compounds were controlled by TLC on silica gel‐precoated aluminum sheets (Type 60 F254, Merck, Darmstadt, Germany), and spots were exposed to iodine vapor. Ethyl 2‐(3‐cyano‐4,6‐dimethylpyridin‐2‐ylthio)acetate ( 4 ) and 2‐(1 H ‐benzo[ d ]imidazol‐2‐yl)‐4‐chloro‐3‐oxobutanenitrile ( 8 ) were prepared according to the previously reported methods.…”

“…0 -(Ethane-1,2-diylbis(azanediyl))bis(4,6-dimethylnicotinonitrile) (14). A mixture of 1 (1.64 g, 10 mmol) and ethane-1,2-diamine (1 mL) in acetonitrile (20 mL) containing Na 2 CO 3 (1 g) was refluxed for 3 h. After cooling, the reaction mixture was poured into ice-water, and the precipitated solid product was filtered off, dried, and recrystallized from ethanol to give compound 14 (71%), mp 83-85 C; IR (KBr) υ (cm Antitumor activity.…”

A Novel Method for the Synthesis of Imidazo[5,1-f][1,2,4]triazin-4(3H)-ones

“…The imidazo [5,1-f] [1,2,4]triazinone scaffold 1 has recently received attention as the core structure of vardenafil (Levitra) (2), a potent and effective PDE5 inhibitor for the treatment of erectile dysfunction. 1 Analogues of this interesting heterocycle containing nitrogen in the ring junction have also been described as muscle relaxants, bronchodilators, 2 as C-nucleoside isosteres, 3 and purine analogues.…”