Facile routes to 1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazines and 1,2,4‐triazino[3,4‐b][1,3,4]thiadiazine by heteropolyacides

Cyclization of 4‐amino‐6‐methyl‐3‐propargylmercapto‐1,2,4‐triazine‐5‐one 3 and 4‐amino‐3‐propargyl mercapto‐1,2,4‐triazole derivatives 6 were afforded 1,2,4‐triazino[3,4‐b][1,3,4]thiadiazines 4 and 1,2,4‐triazolo[3,4‐b][1,3,4]thiadiazines 7 in presence of heteropolyacids, H₁₄[NaP₅W₂₉MoO₁₁₀] and H₆P₂W₁₈O₆₀ in high yields. Among used heteropoly acids, the yields were higher with H₁₄‐P₅Mo, caused to their high acid strengths.     

Synthesis of some [1,2,4]triazino[5,6‐b]quinoline derivatives

By coupling of diazonium salts with ethyl N‐(4‐oxo‐1,4‐dihydroquinolin‐2‐yl)carbamate 4 , the corresponding 3‐arylazocompounds 5 were obtained. These ones were cyclized thermally or in alkaline medium to the corresponding 2‐aryl‐2,3,5,10‐tetrahydro‐[1,2,4]triazino[5,6‐b]quinolin‐3,10‐diones 6 . Compounds 6 were transformed by alkaline hydrolytic splitting to the corresponding 2‐amino‐3‐arylazo‐1,4‐dihydroquino‐lin‐4‐ones 7. Starting carbamate 4 was prepared by a two‐step synthesis from 2‐amino‐1,4‐dihydroquinolin‐4‐one 1.     

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).     

Synthesis of a novel purine‐containing heterocyclic ring system: 8,10‐Dimethylindolo[2′,3′:5,6][1,2,4]triazino[4,3‐f]purine‐9,11(8H, 10H, 13H)‐dione

The preparation of a novel purine containing heterocyclic ring system, indolotriazinopurine, by the condensation of 8‐hydrazinotheophylline with 5‐substituted isatins via the intermediate hemiaminal and hydrazone derivatives, is described.     

Synthesis of new bridgehead heterocycles: Pyrimido[3′,2′:3,4]‐1,2,4‐triazino[5,6‐b]indoles

A new bridgehead nitrogen hetero‐ cycle viz. 11‐carboethoxy‐9‐oxo‐pyrimido[3′2′:3,4]‐1,2,4‐triazino[5,6‐b]indole 3 has been synthesized from 3‐azido‐5H‐1,2,4‐triazino[5,6‐b]indole 2 by its reaction with diethyl fumerate. The intermediate 2 was obtained by treating 3‐hydrazino‐5H‐1,2,4‐triazino[5,6‐b]indole with NaNO₂ in presence of polyphosphoric acid. A plausible mechanism for the formation of 3 has been formulated and discussed. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:272–276, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20199     

Facile synthesis and antifungal activity of 3-substituted 4-amino-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazines and pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepines

The reactions of the pyrazole-5-diazonium salt 3 with malononitrile and ethyl cyanoacetate gave 4-amino-3-cyano-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazine 7 and 4-amino-3,8-bisethoxycarbonylpyrazolo[5,1-c]-[1,2,4]triazine 8 , whose reactions with p-chloroaniline hydrochloride afforded 4-amino-8-ethoxycarbonyl-3-(p-chlorophenyl)amidinopyrazolo[5,1-c][1,2,4]triazine 9 and 4-amino-8-ethoxycarbonyl-3-(p-chlorophenyl)car-bamoylpyrazolo[5,1-c][1,2,4]triazine 10 , respectively. The reactions of 7 and 8 with o-phenylenediamine di-hydrochloride provided 9-ethoxycarbonyl-13H-spiro[benzimidazole-2′(3′H),6(5H)-pyrazolo[1,5′:3,4][1,2,4]tri-azino[5,6-b][1,5]benzodiazepine] hydrochloride 11a and 9-ethoxycarbonyl-6-oxo-13H-5,6-dihydropyrazolo-[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepine 12 , respectively. The antifungal activity of the above compounds was described.     

New 1,2,3‐triazolo[4,5‐d]1,2,4‐triazolo[3,4‐b]pyridazine derivatives II

New tricyclic 1,2,3‐triazolo‐1,2,4‐triazolo‐pyridazine derivatives, bearing a methyl substituent on the 1,2,3‐triazole ring, were prepared as potential biological agents. N‐Methylation of dimethyl 1,2,3‐triazole‐4,5‐dicarboxylate allowed synthesis of the isomeric 1‐methyl‐4,7‐dihydroxy and 2‐methyl‐4,7‐dihydroxy triazolo‐pyridazines 4a and 4b which, by a chlorination reaction, gave the corresponding 1‐methyl‐4‐chloro‐( 6a ), 1‐methyl‐7‐chloro‐ ( 6b ) and 2‐methyl‐4‐chloro‐ ( 9 ) substituted 1,2,3‐triazolo‐pyridazines. The nucle‐ophilic substitution with hydrazine hydrate and the suitable cyclization to form the 1,2,4‐triazole ring, provided the expected tricyclic isomeric derivatives 8a, 8b and 11 respectively. The p‐methoxybenzyl substituent, introduced as a leaving group to obtain either v‐triazolo‐pyridazine or v‐triazolo‐s‐triazolo‐pyri‐dazine derivatives unsubstituted on the 1,2,3‐triazole ring, appeared inadequate. Some compounds underwent binding assays toward the adenosine A₁and A_2A receptors.     

First synthesis of selenadiazolo[3,4‐i] Benzazepine derivatives

5‐Methyl‐4‐nitro‐2,1,3‐benzoselenadiazole ( 1 ) was converted into (E)‐5‐(2‐dimethylamino)vinylbenzo‐[c](1,2,5)selenadiazole‐4‐amine ( 4 ) by initial treatment with dimethylformamide dimethyl acetal (DMFDMA) ( 2 ) followed by selective reduction using ammonium bromide in methanol. Compound 4 afforded the selenadiazolo[3,4‐i][1]benzazepine derivatives ( 7, 10, 13, 15 ) upon treatment with malononitrile ( 5 ), ethyl cyanoacetate ( 8 ) and cyanoacetamide ( 11 ) respectively.     

A convenient synthesis of 2-aryl substituted benzo[f] [1,2,4]triazolo[1,5-a]azepine derivatives

A convenient synthetic pathway to 2-aryl-5,6-dihydro-4H-benzo[f][1,2,4]triazolo[1,5-α]azepine derivatives 7 was developed. The synthesis was based on the cycloaddition of the 1,2,3,4-tetrahydronaphthalene a-acetoxy azo compounds 3 with Ar-CN in the presence of AlCl3 and the consecutive ring enlargement.     

A convenient synthesis of novel 7‐phosphonylbenzyl‐2‐substituted pyrazolo[4,3‐e]‐1,2,4‐triazolo[1,5‐c]‐pyrimidine derivatives

A series of pyrazolo[4,3‐e]‐1,2,4‐triazolo‐[1,5‐c]pyrimidine derivatives, bearing phosphonylbenzyl chain in position 7, were conveniently synthesized in an attempt to obtain potent and selective antagonists for the A_2A adenosine receptor or potent pesticide lead compounds. Diethyl[(5‐amino‐4‐cyano‐3‐methylsulfanyl‐pyrazol‐1‐yl)‐benzyl]phospho‐nate ( 3 ), which was prepared by the cyclization of diethyl 1‐hydrazinobenzylphosphonate ( 1 ) with 2‐[bis(methylthio)methylene]malononitrile ( 2 ), reacted with triethyl orthoformate to afford diethyl[(4‐cyano‐5‐ethoxymethyleneamino‐3‐methylsulfanyl‐pyrazol‐1‐yl)‐benzyl]phosphonate ( 4 ), which reacted with various acyl hydrazines in refluxing 2‐methoxyethanol to give the target compounds 5a–h in good yields. Their structures were confirmed by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. The crystal structure of 5e was determined by single crystal X‐ray diffraction © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:634–638, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20478     

A Facile Synthesis of Aryl‐Substituted Hydrazono‐Pyrazolyl[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin Derivatives

Some inimitable and therapeutic coumarin‐substituted fused[1,2,4]triazolo‐[3,4‐b][1,3,4]thiadizole derivatives were synthesized by the cyclocondensation reaction of 2‐oxo‐2H‐chromene‐3‐carboxylic acid ( 1 ) and 4‐amino‐5‐hydrazinyl‐4H‐[1,2,4]‐triazole‐3‐thiol ( 2 ) by using phosphorous oxychloride as a cyclizing agent. This cyclized intermediate 3‐(3‐hydrazino‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazol‐6‐yl)‐chromen‐2‐one ( 3 ) later condensation with various ethyl 2‐(2‐arylhydrazono)‐3‐oxobutanoates ( 4 ) in NaOAc/MeOH under reflux conditions afforded the corresponding new series of aryl‐substituted hydrazono‐pyrazolyl‐[1,2,4]triazolo[3,4‐b][1,3,4][thiadiazol]‐coumarin derivatives ( 5 ) in good to excellent yields. The structures of newly synthesized compounds were established on the basis of elemental analysis, IR, ¹H NMR and mass spectroscopic studies.     

A Facile Synthesis of Novel Dihydroindeno[1,2‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines Using HTIB

The synthesis of a series of 21 novel 3‐alkyl/aryl‐7/9‐methyl‐10,10a‐dihydroindeno[1,2‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazines ( 4 ) has been achieved by the cyclocondensation between 4/6‐methyl‐2‐tosyloxy‐1‐indanones ( 2 ) and 3‐alkyl/aryl‐4‐amino‐5‐mercapto‐1,2,4‐s‐triazoles ( 3 ). 4/6‐Methyl‐2‐tosyloxy‐1‐indanones ( 2 ) were readily accessible through hypervalent iodine oxidation of 4/6‐methyl‐1‐indanones using [(hydroxy)tosyloxyiodo]benzene (HTIB, Koser's reagent) in acetonitrile.     

Synthesis and reactivity of cyanomethyl 2‐amino‐4‐methylthiazolyl ketone. A facile synthesis of novel pyrazolo[5,1‐c]1,2,4‐triazine, 1,2,4‐triazolo[5,1‐c]1,2,4‐triazine, 1,2,4‐triazino[4,3‐a]benzimidazole,pyridazine‐6‐imine and 6‐oxopyridazinone derivatives

The novel and versatile cyanomethyl 2‐amino‐4‐methylthiazolyl ketone (5) was prepared by treatment of bromomethyl 2‐amino‐4‐methyl thiazolyl ketone (4) with potassium cyanide. Reaction of 5 with heterocyclic diazonium salts 6a,b and 10 afforded the corresponding hydrazones 7a,b and 11, respectively. Refluxing of the hydrazones in pyridine afforded the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine, 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine, and 1,2,4‐triazolo[4,3‐a]benzimidazole derivatives 8a,b and 12, respectively, via intramolecular cyclization. Compound 5 coupled also with benzenediazonium chloride to afford the corresponding hydrazone 14, which is an excellent precursor for the synthesis of pyridazine‐6‐imine 17a and pyridazinone 17b. The pyridazine derivatives 17a,b were also prepared by an independent route, that is, the condensation with malononitriles and coupling with benzenediazonium chloride, followed by intramolecular cyclization. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 385–390, 1999     

Facile Synthesis of New [1,2,4]Triazolo[4,3‐b]pyridazine

A number of new [1,2,4]triazolo[4,3‐b]pyridazines were prepared by either cyclocondesation of substituted hydrazinopyridazines with orthoesters or oxidative cyclization of their hydrazone analogs in nitrobenzene as an oxidizing agent. A host of other new [1,2,4]triazolo[4,3‐b]pyridazine derivatives were synthesized by sequential treatment of the latter compounds with carbon disulfide and alkyl halides.     

A facile synthesis of substituted pyridines and pyrazolo[3,4‐b]pyridines

A facile, solvent free, ecofriendly approach for the synthesis of 2‐amino‐3(ethylcarboxy)‐4,6‐disubsti‐tuted pyridine 4 and pyrazolo[3,4‐b]pyridines 6 is herein described employing neat reaction conditions under microwave irradiation. This solventless methodology is environmentally benign as it completely eliminates the use of solvent from the reaction procedure. The observed reaction rate enhancement and high yield of products are due to the neat reaction conditions coupled with microwaves (MWs).     

Synthesis of Certain 3-Aminopyrazolo[5,4-b]pyridine and 3,4-Substituted Pyrido[2′,3′：3,4]pyrazolo[5,1-c][1,2,4]triazine Derivatives

2-Thioxo-1,2-dihydropyridine derivatives 2a, 2b were reacted with methyl iodide to give 2-methylthiopyridines 3a, 3b, which were reacted with hydrazine hydrate to produce 3-aminopyrazolo[5,4-b]pyridines 4a, 4b. Compounds 4a, 4b were diazotized to afford the corresponding diazonium salts 5a, 5b, which were reacted with some active methylene compounds 6a-6h to give the corresponding pyrido[2′,3′ ： 3,4]pyrazole[5,1-c][1,2,4]triazines 7-14.