5.6.7.8- Tetrahydro-l ,2,4-triazolo

Cyclization of the 3-(2-aminoethyl)-l,2,4-triazoles 60 with aromatic aldehydes gave a mixture of the corresponding Schiff bases 61 and the 5,6,7,8-tetrahydro-l,2,4-triazolo[l,5-c]pyrimidines 62. Cyclization of 60 with car-bonyl-1,1 -diimidazole (CDI) afforded the 5-oxo analogs 63 (92JPR630) (Scheme 22). 

The synthesis of a new series of polyfused l,2,4-triazolo[3,4- ][l,3,4]thiadiazepines by reactions of 3-phenyl-5,6,7,8-tetrahydro[l,2,4]triazolo[3,4-A [l,3,4]thiadiazepine-6,8-dione 98 has appeared <2002PS2871 >. The starting material was obtained in good yield via the reaction of 4-amino-5-phenyl-l,2,4-triazole-3-thione 99 with malonyl... 

A three-component condensation of 3-amino-l, 2,4-triazole (or its 5-Me and 5-methylthio derivatives), 1 and DMF-dimethylacetal afforded 8,9-dihydro[l,2,4]triazolo[l,5-fl]quinazolin-6(7H)-ones (06RCB1224). Condensation of 3,4,5-triamino-l,2,4-triazole with aromatic aldehydes and dimedone afforded partially hydrogenated 9-aryl-[l,2,4]triazolo[5,l-frJquinazolin-8-ones. The structure of 2-amino-6,6-dimethyl-3-(4-nitro-benzylidene)amino-9-(4-nitrophenyl)-5,6,7,9-tetrahydro[l,2,4]triazolo[5,l-fr]-quinazolin-8-one was confirmed by X-ray analysis (05RCB2903). 

Tetrahydro-[l,2,4]triazolo[4,3-h]cinnolines have been prepared from 3-hydrazino-5,6,7,8-tetrahydrocinnolines and the reagents just described for (17) (71BSF3043), and also by condensing 2-hydroxymethylenecyclohexanone with 4-amino-1,2,4-triazole (79JCS(P1)3085). 

Tetrahydro-3-triazolo[4,3-b][l,2,4Jtriazine>6,7-diones from 3,4-diamino-l,2,4-triazoles... 

Sitagliptin phosphate monohydrate (1, 7-[(3i )-3-amino-l-oxo-4-(2,4,5-trifluoro-phenyl)butyl]-5,6,7,8-tetrahydro-3-(trifluoromethyl)-l,2,4-triazolo[4,3-a]pyrazine phosphate monohydrate, Januvia ) is an oral hypoglycaemic drug, an inhibitor of the dipeptidyl peptidase-IV (DPP4) enzyme. It is widely used in the therapy of type 2 diabetes mellitus [1,2]. 

Isothiocyanato-3,3-dimethylbutan-2-one (87) provided the C4N3 fragment that gave, upon reaction with 2-ethylthiosemicarbazide (CN3 fragment) (88), the 3-ethyl-l,6,7,8a-tetrahydro-2,5-dithioxo-8,8,8a-trimethyl-l,2,4-triazolo[l,5-c]pyrimidine 89 (76M1241) (Scheme 33). 

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). 

Preparation of 6-(2-chlorophenyl)-9-ethoxycarbonyl-l-methyl-7,8,9,10-tetrahydro-4H-pyrido[4, 3 4,5]thieno[3,2-f]-l,2,4-triazolo[4,3-a]-l,4-diazepine... 

A tandem aza-Wittig/heterocumulene-mediated annulation route was developed for the efficient production of 6,7,8,9-tetrahydro-benzothieno[2,3-r/]-l,2,4-triazolo[l,5-a]pyrimidin-10(3F/)-ones <05S1601>, and an amine oxide rearrangement was key to the regioselective preparation of pyrrolo[2,3-J]pyrimidines <0581164>. Hexahydro-2-phenacylidene-pyrimidines gave -lactam fused 8-aroyl-2,3,4,5-tetrahydro-7-hydroxy-6//-pyrrolo[l,2-a]py-rimidine-6-ones when treated with (COCl), in the presence of NaH <05IJH87>, and methyl... 

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