Synthesis of 4‐(1‐phenyl‐1H‐pyrazol‐3‐yl)‐[1,2,4]triazolo[4,3‐a]quinoxalines and their 4‐halogenopyrazolyl analogs

Synthesis of {3‐[1‐(ethoxycarbonyl)‐[1,2,4]triazolo[4,3‐a]quinoxalin‐4‐yl]‐1‐phenyl‐1H‐pyrazol‐5‐yl}methyl ethyl oxalate ( 2 ), ethyl 4‐[5‐(acetoxymethyl)‐1‐phenyl‐1H‐pyrazol‐3‐yl]‐[1,2,4]triazolo[4,3‐a]quioxaline‐1‐carboxylate ( 4 ), [4‐halo‐1‐phenyl‐3‐(1‐phenyl‐[1,2,4]triazolo[4,3‐a]quioxalin‐4‐yl)‐1H‐pyrazol‐5‐yl]methyl acetate ( 11 ), {4‐halo‐3‐[1‐methyl‐[1,2,4]triazolo[4,3‐a]quinoxalin‐4‐yl]‐1‐phenyl‐1H‐pyraz‐ol‐5‐yl}methyl acetate ( 13 ), and [3‐([1,2,4]triazolo‐[4,3‐a]quinoxalin‐4‐yl)‐4‐halo‐1‐phenyl‐1H‐pyrazol‐5‐yl] methyl formate ( 15 ) was accomplished. The structural investigation of the new compounds is based on chemical and spectroscopic evidences. J. Heterocyclic Chem., (2011)     

Isolation and structural data of the opened ring derivative of a 1,2,4‐triazolothieno‐1,4‐diazepine

The preparation of the trihydrochloride form of 2‐[3‐(aminomethyl)‐5‐methyl‐1,2,4‐triazol‐4‐yl]‐3‐(2‐chlorobenzoyl) thieno[2,3‐c]‐4,5,6,7‐tetrahydropyridine ( 2 ) the ring opened derivative of a 1,2,4‐triazolo‐thieno‐1,4‐diazepine is described. Its structural properties are given, and are compared with those of the corresponding closed form 4H‐6‐(2‐chlorophenyl)‐1‐methyl‐7,8,9,10‐tetrahydropyrido[4′,3′:4,5]thieno[3,2‐f]‐[1,2,4]triazolo[4,3‐a][1,4]diazepine ( 1 ).     

Synthesis of some novel pyrazolo[1,5‐a]pyrimidine, 1,2,4‐triazolo[1,5‐a]pyrimidine,pyrido[2,3‐d]pyrimidine,pyrazolo[5,1‐c]‐1,2,4‐triazine and 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine derivatives incorporating a thiazolo[3,2‐a]benzimidazole moiety

E‐3‐(N,N‐Dimethylamino)‐1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)prop‐2‐en‐1‐one ( 2 ) was synthesized by the reaction of 1‐(3‐methylthiazolo[3,2‐a]benzimidazol‐2‐yl)ethanone ( 1 ) with dimethylformamide‐dimethylacetal. The reaction of 2 with 5‐amino‐3‐phenyl‐1H‐pyrazole ( 4a ) or 3‐amino‐1,2,4‐(1H)‐triazole ( 4b ) furnished pyrazolo[1,5‐a]pyrimidine and 1,2,4‐triazolo[1,5‐a]pyrimidine derivatives 6a and 6b , while the reaction of enaminone 2 with 6‐aminopyrimidine derivatives 7a,b afforded pyrido[2,3‐d]pyrimidine derivatives 9a,b , respectively. The diazonium salts 11a or 11b coupled with compound 2 to yield the pyrazolo[5,1‐c]‐1,2,4‐triazine and 1,2,4‐triazolo[5,1‐c]‐1,2,4‐triazine derivatives 13a and 13b . Some of the newly synthesized compounds exhibited a moderate effect against some bacterial and fungal species.     

New 1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidine derivatives II

The 7‐chloro‐3‐(2‐chlorobenzyl)‐ and 7‐chloro‐3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐d]pyrimidines ( 1 and 4 ), by nucleophilic replacement with some hydrazides, gave the corresponding 7‐hydrazidoderivatives ( 2a‐e and 5a‐e ). These, by heating in Dowtherm, underwent an intramolecular cyclization to form the new tricyclic 7‐substituted‐3‐(2‐chlorobenzyl)‐ and 3‐(2‐fluorobenzyl)‐1,2,3‐triazolo[4,5‐e]1,2,4‐triazolo[4,3‐c]pyrimidines ( 3a‐d and 6a‐d ). The 7‐hydrazino‐3‐(2‐chlorobenzyl)‐ and 7‐hydrazino‐3‐(2‐fluorobenzyl)‐triazolo‐pyrimidines ( 9a and 9b ) were also prepared via the corresponding mercapto ( 7a and 7b ) and thiomethyl ( 8a and 8b ) derivatives.     

A new approach for the synthesis of some pyrazolo[5,1‐c]triazines and pyrazolo[1,5‐a]pyrimidines containing naphtofuran moiety

Naphtho[2,1‐b]furan‐2‐yl)(8‐phenylpyrazolo[5,1‐c][1,2,4]triazin‐3‐yl)methanone, ([1,2,4]triazolo[3,4‐c][1,2,4]triazin‐6‐yl)(naphtho[2,1‐b]furan‐2‐yl)methanone, benzo[4,5]imidazo[2,1‐c][1,2,4]triazin‐3‐yl‐naphtho[2,1‐b]furan‐2‐yl‐methanone, 5‐(naphtho[2,1‐b]furan‐2‐yl)pyrazolo[1,5‐a]pyrimidine, 7‐(naphtho[2,1‐b]furan‐2‐yl)‐[1,2,4]triazolo[4,3‐a]pyrimidine, 2‐naphtho[2,1‐b]furan‐2‐yl‐benzo[4,5]imidazo[1,2‐a]pyrimidine, pyridine, and pyrazole derivatives are synthesized from sodium salt of 5‐hydroxy‐1‐naphtho[2,1‐b]furan‐2‐ylpropenone and various reagents. The newly synthesized compounds were elucidated by elemental analysis, spectral data, chemical transformation, and alternative synthetic route whenever possible. J. Heterocyclic Chem., (2012).     

Design and Synthesis of Some Novel 2,3,4,5‐Tetrahydro‐1H‐pyrido[4,3‐b]indoles as Potential c‐Met Inhibitors

Since deregulation of the tyrosine‐kinase receptor c‐Met is implicated in several human cancers and is an attractive target for small‐molecule‐drug discovery, we report herein the synthesis of 2,3,4,5‐tetrahydro‐8‐[1‐(quinolin‐6‐ylmethyl)‐1H‐1,2,3‐triazolo[4,5‐b]pyrazin‐6‐yl]‐1H‐pyrido[4,3‐b]indoles 4a – 4c and 2,3,4,5‐tetrahydro‐8‐[3‐(quinolin‐6‐ylmethyl)‐1,2,4‐triazolo[4,3‐b]pyridazin‐6‐yl]‐1H‐pyrido[4,3‐b]indoles 5a – 5c . These indole derivatives demonstrated inhibition of c‐Met kinase activity. Concurrently, five key intermediates were synthesized. These compounds could be prepared in good yields.     

A Convenient Synthesis of NovelDerivatives of Pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-5,6-dione

Summary.  Reaction of 6-Amino-2-thiouracil with hydrazonoyl halides yielded regioselectively 7-amino-1,3-disubstituted-1,2,4-triazolo[4,3-a]pyrimidine derivatives. Upon treatment with methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate, the corresponding methyl (Z)-2-benzoylamino-3-([1,2, 4]triazolo[4,3-a]pyrimidin-7-yl)-amino propenoates were obtained which cyclized in the presence of sodium ethoxide to afford novel derivatives of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-5,6-(1H,8H)-diones. E-mail: mosselhi@chem-sci.cairo.eun.eg Received February 8, 2002; accepted (revised) March 18, 2002     

Synthesis of New [1,2,4]Triazolo[1,5‐a]pyrimidine Derivatives: Reactivity of 3‐Amino[1,2,4]triazole towards Enaminonitriles and Enaminones

A diversity of new 7 ‐substituted[1,2,4]triazolo[1,5‐a]pyrimidine and 6‐substituted[1,2,4]triazolo[1,5‐a]pyrimidine‐7‐amine derivatives has been synthesized via reaction of 3‐amino‐[1,2,4]triazole with enaminonitriles and enaminones. The regio orientation and the structure of the products were confirmed by spectral and analytical data and synthesis via an alternative route. The procedure proved to be simple, efficient, and high yielding, and diversities of [1,2,4]triazolo[1,5‐a]pyrimidines were obtained.     

Formylation of 4,7‐Dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines Using Vilsmeier–Haack Conditions

Formylation of 5‐methyl‐7‐phenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidine 1a using Vilsmeier–Haack conditions yields 5‐methyl‐7‐phenyl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidin‐6‐ylcarbaldehyde 3a . 5,7‐Diaryl‐4,7‐dihydro‐1,2,4‐triazolo[1,5‐a]pyrimidines 1b , 1c in this reaction apart from formylation undergo recyclization into 5‐aryl‐1,2,4‐triazolo[1,5‐a]pyrimidin‐6‐ylmethane derivatives 4b , 4c , 5b , 5c , and 6 . The structure of the synthesized compounds was determined on the basis of NMR, IR, and MS spectroscopic data and confirmed by the X‐ray analysis of the 6‐(ethoxy‐phenyl‐methyl)‐5‐phenyl‐[1,2,4]triazolo[1,5‐a]pyrimidine 6 , 5‐phenyl‐6‐(1‐phenyl‐vinyl)‐[1,2,4]triazolo[1,5‐a]pyrimidine 11 , and 7‐phenyl‐6‐(1‐phenyl‐vinyl)‐[1,2,4]triazolo[4,3‐a]pyrimidine 12 .     

Synthesis,design, and antimicrobial activity of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidinones based on quinoline derivatives

The pyrido[2,3-d]pyrimidine moieties are one of the most biologically widespread heterocyclic compounds as antimicrobial, antioxidant, antitubercular, antiviral and anti-inflammatory. Hence, we synthesized an efficient new series of 2-thioxo-pyrido[2,3-d]pyrimidinone, 2-hydrazinyl-(quinolin-2-yl)pyrido[2,3-d]pyrimidinone,N′-(quinolin-2-yl)-pyrido[2,3-d]pyrimidine-(formo/aceto)-hydrazide and substituted-(quinolin-2-yl)pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidinone derivatives. The characterization of new compounds was corresponded by using spectroscopic techniques, IR, NMR and Mass spectra. In vitro, all compounds were evaluated as antimicrobial activity compared with cefotaxime sodium and nystatin as the standard drug. This work deals with the exploration of the new heterocyclic compounds and medicinal diversity of quinoline-pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine derivatives that might pave the way for long in the discovery of therapeutic medicine for future drug design.     

Synthesis of new 1‐phenylthieno[1,2,4]triazolo[4,3‐a]pyrimidin‐5(4H)‐one derivatives

A series of novel 1‐phenylthieno[1,2,4]triazolo[4,3‐a]pyrimidin‐5(4H)‐one derivatives 5 and 6 were synthesized by oxidative cyclization of thienopyrimidinonyl hydrazones using iodobenzene diacetate. J. Heterocyclic Chem., (2011).     

Product and Mechanism of Gas‐phase Pyrolysis of 2‐arylidinehydrazinopyrimidines: Interesting Route to Condensed Heterocycles[1]

Gas‐phase pyrolysis of N‐arylidine‐N′‐pyrimidin‐2‐yl‐hydrazine derivatives 1a , 1b , 1c , 1d , 1e gave the corresponding arylnitriles 2a , 2b , 2c , 2d , 2e , 2‐aminopyrimidine 3 , 3‐phenyl‐1,2,4‐triazolo[4,3‐a]pyrimidines 4 , 2‐phenyl‐1,2,4‐triazolo[1,5‐a]pyrimidines 5 , 2,4,5‐triphenyl‐1H‐imidazole 6 , and 2,3‐diphenylquinoline 7 . The analyses of the reaction products are reported and used to elucidate the mechanism of the pyrolytic process.     

A Convenient Synthesis of NovelDerivatives of Pyrido[2,3- d ][1,2,4]triazolo[4,3- a ]pyrimidine-5,6-dione

 Reaction of 6-Amino-2-thiouracil with hydrazonoyl halides yielded regioselectively 7-amino-1,3-disubstituted-1,2,4-triazolo[4,3-a]pyrimidine derivatives. Upon treatment with methyl (Z)-2-benzoylamino-3-dimethylaminopropenoate, the corresponding methyl (Z)-2-benzoylamino-3-([1,2, 4]triazolo[4,3-a]pyrimidin-7-yl)-amino propenoates were obtained which cyclized in the presence of sodium ethoxide to afford novel derivatives of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine-5,6-(1H,8H)-diones.     

Synthèse et étude physicochimique des 1,2,4-triazolo[4,3-a]-pyridines et des 1,2,4-triazolo[2,3-a]pyridines

The synthesis of 1,2,4-triazolo[4,3-a] and [2,3-a]pyridines 7, 8 was achieved by cyclization of 2-hydrazino-8-nitropyridine 3a with formic acid. The 4,5,6,7-tetrahydro-1,2,4-triazolo[2,3-a]pyridine 13 and 8-amino-1,2,4-triazolo[2,3-a]pyridine 9 were obtained by catalytic hydrogenation. The reduction of triazolo pyridine 8 using stannous chloride led to the intermediate compound 10 which with acetic anhydride afforded 8-acetylamino-5-chloro-1,2,4-triazolo[2,3-a]pyridine 10a . The structure of the derivatives was determined by ¹H-nmr (DMSO-d₆).     

Regioselective synthesis and characterization of new 3‐aryl‐7‐trifluoromethyl‐[1,2,4]triazolo[4,3–a]pyrimidines

The regioselective synthesis and characterization of a new series of 3‐aryl‐7‐trifluoromethyl[1,2,4]triazolo[4,3–a]pyrimidines from the oxidative heterocyclization of 2‐(N′‐benzylidenehydrazino)‐4‐trifluoromethylpyrimidines with copper dichloride is described. J. Heterocyclic Chem., (2011).     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 8 . [1]Benzothieno[2,3-c]naphtho[1,2-h]quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline

The previously unknown polycyclic heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[1,2-h]-quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline were synthesized via photocyclization of 3-chloro-N-(1′-phenanthryl)benzo[b]thiophene-2-carboxamide.     

Synthesis and Spectral Characteristics of Novel Fluorescent Dyes Based on Pyrimido[4,5‐d] [1,2,4]triazolo[4,3‐a]pyrimidine

Different derivatives of a novel heterocyclic system, i.e., pyrimido[4,5‐d] [1,2,4]triazolo[4,3‐a]pyrimidine, are synthesized in moderate‐to‐good yields. These compounds exhibit excellent photochromism upon photoirradiation. The photophysical characterizations of these new compounds were evaluated by UV/VIS absorption and fluorescence emission studies. The emission spectra in various solvents are also presented and discussed. The changes are due to the intramolecular H‐bonding of pyrimido‐triazolo‐pyrimidine with H₂O, and photoinduced electron and general solvent effect. These compounds display high fluorescence quantum yields and are reported as new fluorophores.     

Bis(enaminones) as Versatile Precursors for Novel Bis([1,2,4]triazolo[1,5‐a]pyrimidines) and Bis(2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐ones)

Novel bis([1,2,4]triazolo[1,5‐a]pyrimidines) and bis(2‐thioxo‐2,3‐dihydropyrido[2,3‐d]pyrimidin‐4(1H)‐ones) were prepared utilizing bis(enaminones) as precursors. The structures of the prepared compounds were elucidated by several spectral tools as well as elemental analyses.     

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 new convenient synthesis of 2,4‐disubstituted‐1,2,4‐triazolo[1,5‐a] quinazolin‐5(4H)‐ones

A novel series of 2,4‐disubstituted‐1,2,4‐triazolo[1,5‐a]quinazolin‐5(4H)‐ones were prepared by Dimroth rearrangement of their respective isomers namely 1,4‐disubstituted‐[1,2,4]triazolo[4,3‐a]‐quinazolin‐5(4H)‐ones. The latter were prepared via new synthetic strategy based on 1,5‐elecrocyclization of the respective N‐(4‐oxo‐3‐phenylquinazolin‐2‐yl)nitrilimines.