1.2.4- Triazolo diazepin-8-ones

Garanti et al. (30a) reported a synthesis of the l,2,3-triazolo[l,5-a][4.1]benzox-azepine 149 via an intramolecular cycloaddition of an aryl azide with an acetylene (Scheme 9.30). By using a similar strategy, the l,2,3-triazolo[l,5-a][l,4-l ]benzo-diazepine 150, an analogue of Flumazenil, was also reported (30b,c). As an extension of this method, the l,2,3-triazolo[l,5-a][l,4]benzodiazepine-6-one 153 was synthesized using an intramolecular 1,3-dipolar cycloaddition of an azide with a cyano group (30d). 

On heating the condensed [l,2,4]-triazolo[4,3- ]pyridazine-6(577)-one-3(27/)-thione 91 with dialkyl acetylenedi-carboxylates in DMF, the subsequent ring transformations yielded the novel tetracyclic 1,3-diazepine cis-92, which can further be converted to 93 in a number of steps involving elimination, decarboxylation, and cyclization oxidation upon heating (Scheme 15) <2001T7191>. 

Compound 98 was condensed with o-aminothiophenol, 2-aminoethanol, or cystamine in refluxing diphenyl ether through an intermolecular cyclization with the elimination of two molecules of water to give the polyfused derivatives 101-103, respectively. Also, the reactions of 98 with dimethylthiomethylenemalononitrile in boiling dimethylforma-mide (DMF) were studied. The dimethylthiomethylenemalononitrile was prepared via the reaction of malononitrile with CS2 with 2 equiv of methyl iodide in a one-pot reaction using liquid-liquid phase-transfer catalysis (PTC) technique (NaOH/dioxane/tetrabutylammonium bromide (TBAB)). The product of this reaction was identified as 8-cyano-9-imino-7-methylthio-6-oxo-3-phenyl-5,6,8,9-tetrahydro-77/-pyrano[3,2-/][l,2,4]-triazolo[3,4-A][l,3,4]thia-diazepine 104 (Scheme 10). 

Amino-N-cyanomethyl-3-thiophenecarboxamide (216), easy accessible according to the Gewald method,21 cyclizes in the presence of sodium methoxide to give 2-amino-3,4-dihydrothieno[2,3-/]-l,4-diazepine-5-one (217), which is converted with acetylhydrazine to a thieno[3,2-/][l,2,4]-triazolo[4,3-a][l,4]diazepine-6-one (218).129 These compounds are of interest because of their hypnogenic and anxiolytic properties (Scheme 56). By a one-step procedure, 2-aminothiophene-3-carboxylates 219 are transformed with cyclohexanone by heating with HMPT and catalytic amounts of PPA to 4-dimethylamino-2-methyl-5,6,7,8-tetrahydrothieno[2,3-b]quino-lines such as 220.130... 

Finally, when the reaction on 125 was carried out using guanidine l,2,3-triazolo[4,5-e]-l,3-diazepin-4-one 132 was obtained. These pseudonucleosides were tested against 60 human tumor cell Unes, but showed poor or no anticancer activity [127]. 

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