Azinoiminophosphorane mediated synthesis of 5H, 7H‐1,2,4‐triazolo[1,5‐c][1,3]benzoxazepin‐7‐ones and 6H,8H‐1,2,4‐triazolo‐[1,5‐c][1,3]oxazepin‐6‐ones

The aza‐Wittig reactions of benzophenone‐, acetophenone‐ and benzaldehyde l‐[(triphenylphosphoranyl‐idene)amino]ethylidenehydrazones (4) with phthalic anhydride, 2,3‐dimethylmaleic anhydride and 7‐oxabi‐cyclo[2,2,l]hept‐5‐ene‐2,3‐dicarboxylic anhydride ( 5a ) provide a new route to 5H,7H‐1,2,4‐triazolo[1,5‐c]‐[1,3]benzoxazepin‐7‐ones 8a‐c or 6H,8H‐1,2,4‐triazolo[1,5‐c][1,3]oxazepin‐6‐ones 8d‐h via the thermal reaction of the expected azinoimine lactones 6 .     

Synthesis and Biological Activities of 7‐Arylazo‐7H‐pyrazolo[5,1‐c][1,2,4] Triazol‐6(5H)‐Ones and 7‐Arylhydrazono‐7H‐[1,2,4]triazolo[3,4‐b] [1,3,4]thiadiazines

Two series of 7‐arylazo‐7H‐3‐(2‐methyl‐1H‐indol‐3‐yl)pyrazolo[5,1‐c][1,2,4]triazol‐6(5H)‐ones 4 and 7‐arylhydrazono‐7H‐3‐(2‐methyl‐1H‐indol‐3‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines 7 were prepared via reactions of 4‐amino‐3‐mercapto‐5‐(2‐methyl‐1H‐indol‐3‐yl)‐1,2,4‐triazole 1 with ethyl arylhydrazono‐chloroacetate 2 and N‐aryl‐2‐oxoalkanehydrazonoyl halides 5 , respectively. A possible mechanism is proposed to account for the formation of the products. The biological activity of some of these products was also evaluated.     

On triazoles XLIX. Synthesis of 5,6‐dihydrothiazolo[3,2‐b]‐[1,2,4]triazol‐2‐yl‐, 6,7‐dihydro‐5H‐[1,2,4]triazolo[5,1‐b][1,3]thiazin‐2‐yl‐, and 5,6,7,8‐tetrahydro[1,2,4]triazolo[5,1‐b] [1,3]thiazepin‐2‐yl‐isoquinolinium salts

5′‐Mercapto‐1′H‐1,2,4‐triazol‐3′‐yl‐isoquinolinium salts (6) were synthesised by the reaction of ortho‐acyl phenylacetones (2) or the corresponding pyrylium salts (3) and 5‐amino‐2,3‐dihydro‐1H‐1,2,4‐triazole‐3‐thione (5) . Treatment of thioles 6 withα,ω‐dibromoalkanes led to type 15, 16 and 17 isoquinolinium salts condensed with thiazole, thiazine and thiazepine rings. When 6 are reacted with dibromomethane (10) 11 type dimeric structures are obtained.     

Synthesis and antifungal activity of novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b][1,2,4]triazepines

5‐Aryl‐3,4‐diamino‐1,2,4‐triazoles 5 on treatment with β‐chlorocinnamaldehydes 7 in the presence of catalytic amount of p‐TsOH and N,N‐dimethylformamide as an energy transfer medium under microwave irradiation and as solvent with oil‐bath heating at 80 °C affords novel 3,6‐diaryl‐5H‐[1,2,4]triazolo[4,3‐b]‐1,2,4]triazepines 8 . The structures of the synthesized compounds were established on the basis of ¹H NMR, IR, mass spectral data and elemental analysis.     

Synthesis of Substituted 5,6-Dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines

A one-pot synthetic approach to the novel 5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepines by thermal cyclization of 4-acylhydrazino-2,3-dihydro-1H-1,5-benzodiazepines is described.     

Short Synthesis of Enantiopure Thieno[2,3‐f]triazolo[1,5‐a][1,4]diazepines and Thieno[2,3‐f][1,4]diazepin‐5‐ones

Starting from 2‐carboxy‐3‐thenylazide 1 and enantiopure amines 2 as the chiral building blocks, we developed a two‐step synthesis of the title compounds involving an intramolecular azide cycloaddition as the key step.     

Synthesis of some pyrazolo[1,5‐c][1,3]benzoxazines and a new 5H‐pyrazolo[1,5‐c][1,3,2]benzoxazaphosphorine ring system

Condensations of 5‐(2‐hydroxyphenyl)pyrazoline 3a with 4‐carboxybenzaldehyde, glyoxylic acid and N,N‐carbonyldiimidazole leading to pyrazolobenzoxazine derivatives were studied. The observed diastere‐oselectivity is discussed. Reaction of 3a with Lawesson reagent gave rise to a new 5H‐pyrazolo[1,5‐c]‐[1,3,2]benzoxazaphosphorine heterocyclic system.     

Synthesis of novel 2‐alkoxy(aralkoxy)‐4H‐[1,2,4]triazolo[1,5‐a]quinazolin‐5‐ones starting with dialkyl‐N‐cyanoimidocarbonates

A novel series of 2‐alkoxy(aralkoxy)‐4H‐[1,2,4]triazolo[1,5‐a]quinazolines were synthesized employing N‐cyanoimidocarbonates and 2‐hydrazinobenzoic acid as building blocks. Chemical transformation of the inherent lactam moiety in the targeted 2‐alkoxy(aralkoxy)[1,2,4]triazolo[1,5‐a]quinazolines was offered access to a variety of derivatives. J. Heterocyclic Chem., (2011).     

Synthesis of some novel 3,7‐dimethyl‐4H‐pyrazolo[5,1‐c][1,2,4]triazin‐4‐ones

Some novel 3,7‐dimethyl‐6H‐pyrazolo[5,1‐c][1,2,4]triazin‐4‐ones were prepared (3a‐g) . Compounds 3a,b were treated with hydrazines to afford various products 7a,b, 8a,b, 9 and lla,b depending on the type of hydrazine derivative and reaction conditions. The benzoyloxyimino‐pyrazolo[5,1‐c][1,2,4]triazines (13a,b) were synthesized by refluxing of compounds 3a,b with hydroxylamine hydrochloride to afford the corresponding oxime derivatives followed by treatment with benzoyl chloride.     

Facile one‐pot synthesis of [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines and 3,7‐dimethyl‐4H‐[1,2,4]triazino[3,4‐b][1,3,4]thiadiazin‐6‐one using heteropolyacid catalysts

[1,2,4]Triazolo[3,4‐b][1,3,4]thiadiazines 2a , 2b , 2c , 2d , 2e , 2f and 3,7‐dimethyl‐4H‐[1,2,4]triazino[3,4‐b][1,3,4]thiadiazin‐6‐one 4 were synthesized by one‐pot cyclocondensation reaction with α‐chloroacetonitrile and α‐haloketones in the presence of catalytic amounts of heteropolyacids in very high yields and rates. J. Heterocyclic Chem., (2011).     

Preparation of substituted 1,3‐dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐ones

A new synthetic route to 6‐substituted‐imidazo[4,5‐c]pyridin‐2‐ons from 4‐aminopyridine has been investigated. 4‐Aminopyridine protected as alkyl carbamates were nitrated with dinitrogen pentoxide to the corresponding methyl, i‐propyl and t‐butyl 3‐nitropyridin‐4‐yl carbamates ( 5a‐c ) in 51‐63 % yields. Attempts to substitute these in the 6‐position by the ONSH and the VNS techniques succeeded with butyl‐amine and the t‐butyl carbamate 9 . From the methyl or t‐butyl 3‐nitropyridin‐4‐yl carbamates 5a, 5c 1,3‐dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐one ( 1 ) was formed in 73 and 39 % yields, respectively. t‐Butyl 6‐N‐butylamin‐3‐aminopyridin‐4‐yl carbamate ( 6 ) gave 6‐butylamino‐1,3‐dihydro‐2H‐imidazo[4,5‐c]‐pyridin‐2‐one (7) in 53 % yield.     

Synthesis and antibacterial studies of 6‐aryl‐2,2a‐dihydro‐naphtho‐[2′,1′‐5,6]pyrano[4,3‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine and its derivatives

Chemoselective synthesis of novel hetero cyclopenta[b]chrysene derivatives, namely, 6‐Aryl‐2,2a‐dihydro‐naphtho[2′,1′‐5,6]pyrao[4,3‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine ( 4a‐j ) under neutral condition has been described. These molecules exhibited good to excellent anti‐bacterial activities.     

Synthesis and structure characterization of new [1,2,4]triazolo[5,4‐d][1,5]benzothiazepine derivatives through 1,3‐dipolar cycloaddition reaction

Reaction of 1,5‐benzothiazepines 3 , obtained from chalcones 2 and o‐aminobenzenthiol, with the (phenylhydrazino) chloromethylenecarboxylates 4 in the presence of Et₃N leads to a series of new [1,2,4]triazolo[5,4‐d][1,5]benzothiazepine derivatives 5 . Their structures were established using spectroscopic methods and that of compound 5d was confirmed using X‐ray diffraction analysis. J. Heterocyclic Chem., (2011).     

Synthesis and rearrangements of 7H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]-and 7h-pyrrolo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidines

7H-Pyrrolo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines were synthesized by the reactions of 2-ethoxymethyleneamino-1H-pyrrole-3-carbonitriles with acid hydrazides and by the reactions of aminoiminopyrimidines (prepared based on the above-mentioned carbonitriles) with acid chlorides. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1438–1443, August, 2006.     

New [g]-fused [1,2,4]triazolo[1,5-c]pyrimidines: Synthesis of pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-c]pteridine derivatives

A number of 2-aryl-substituted pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-c]pteridines 11,12a,b,e , their corresponding 5-carbonyl derivatives 7,8a,b,e and some pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5-ones 7,8c,d have been synthesized, according to different pathways. The new tricyclic heterocycles were prepared with the aim of studying their possible benzodiazepine receptors affinity.     

Synthesis of Imidazo[2,1‐b][2H‐1,3,4]thiadiazines and 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines

Imidazo[2,1‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 2‐amino‐5‐(4‐chlorophenyl)‐6H‐1,3,4‐thiadiazine with α‐haloketones. 1,2,4‐Triazolo[3,4‐b][2H‐1,3,4]thiadiazines were prepared by cyclization of 4‐amino‐5‐sulfanyl‐l,2,4‐triazoles with phenacyl bromides.     

Synthesis of new derivatives of 3‐aryl‐1,5‐dimethyl‐1H‐[1,2,4]triazolo[4′,3′:1,2]pyrimido[4,5‐e][1,3,4]oxadiazines as potential antiproliferative agents

Starting from pyrimido[4,5‐e][1,3,4]oxadiazines ( 3a , 3b , 3c ) , a synthetic pathway to [1,2,4]triazolo[4′,3′:1,2]pyrimido[4,5‐e][1,3,4]oxadiazines ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i ) is described. The reaction of pyrimido[4,5‐e][1,3,4]oxadiazines ( 3a , 3b , 3c ) with hydrazine hydrate afforded the corresponding hydrazino derivatives ( 4a , 4b , 4c ) . Further treatment of these compounds with different orthoesters in acetic acid gave the corresponding [1,2,4]triazolo[4′,3′:1,2]pyrimido[4,5‐e][1,3,4]oxadiazines ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i ) . Compound ( 3a ) and ( 5b ) , as examples, were tested on different cancer cell lines including HeLa, MCF‐7, and HepG2. Malignant cells were cultured in DMEM medium and incubated with different concentrations of the titled compounds. Cell viability was quantitated by MTT assay. J. Heterocyclic Chem., (2010).