Synthesis of arylamino-substituted pyrazolo[3,4-d][1,2,4]triazolo[4,3-a]pyrimidinones,pyrazolo[4,3-e][1,2,4]triazolo[4,3-a]pyrimidinones,and their thermal isomerization

The reaction of 1-(4-oxo-1-R-5H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-arylthiosemicarbazides with methyl iodide gave rise to 1,2,4-triazolo-pyrazolopyrimidinones of linear structure, and with dicyclohexylcarbodiimide the products had angular and linear structure. The heating of compounds obtained higher than their melting point resulted in their isomerization into 7-aryl-amino-1-R-1,8-dihydro-4H-pyrazolo[3,4-d]-[1,2,4]triazolo[1,5-a]pyrimidin-4-ones.     

On triazoles XXIV . Synthesis of cycloalka[1,2,4]triazolo[1,5-a]pyrimidinones

The uv and nmr spectral data of some 6,7,8,9,10,11-hexahydrocyclohepta[d][1,2,4]triazolo[1,5-a]pyrimidin-5-one, 5,6,7,8,9,11-hexahydrocyclohepta[e][1,2,4]triazolo[1,5-a]pyrimidin-10-one, 6,7,8,9,10,11-hexahydrocycloocta[d][1,2,4]triazolo[1,5-a]pyrimidin-5(12H)-one, 5,6,7,8,9,10-hexahydrocycloocta[e][1,2,4]triazolo[1,5-a]-pyrimidin-11(12H)-one, 6,7,8,9,10,11,12,13,14,15-decahydrocyclododeca[d][1,2,4]triazolo[1,5-a]pyrimidin-5(16H)-one and 5,6,7,8,9,10,11,12,13,14-decahydrocyclododeca[e][1,2,4]triazolo[1,5-a]pyrimidin-15(16H)-one as well as their N-benzylated derivatives representing six novel ring systems were compared to prove their structure. The N-benzylation of the highly insoluble cyclic amides to yield the isomeric N-benzyl derivatives 3/1, 3/2 and 3/3 distinguished by INAPT was performed through their readily soluble tetrabutylammonium salts.     

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,Antibacterial, and Antifungal Activities of Imidazo[2,1-c][1,2,4]triazoles and 1,2,4-Triazolo[4,3-a]pyrimidinones

A straightforward method has been developed for the synthesis of 1-phenyl-imidazo [2,1-c][1,2,4]triazole derivatives 5a–j and 1-phenyl-[1,2,4]triazolo[4,3-a]pyrimidinones derivatives 6a–g starting from 5-amino-1-phenyl[1,2,4]triazole and p-toluenesulfonic acid (PTSA). This methodology affords a number of 1-phenyl-imidazo [2,1-c][1,2,4]triazoles 5a–j and 1-phenyl-[1,2,4]triazolo[4,3-a]pyrimidinones 6a–g in reasonable yields and short reaction times. The structures of all new compounds were elucidated using infrared, ¹H and ¹³C NMR, and high-resolution mass spectrometry. Some of the newly synthesized compounds were screened for their antimicrobial activity.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications ^® for the following free supplemental resource(s): Full experimental and spectral details.]     

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.     

A new heterocyclic structure. The [1,2,3]triazolo[1,5-d][1,2,4]triazine

The hydrazone derivatives of 4-benzoyl-1,2,3-triazole can easily be cyclised by reaction with various organic reagents (ortho esters, aldehyde and ketone compounds, phosgene, etc) which result in the incorporation of the introduced reagent's carbon atom into the new six membered ring. The newly created C-N bond of the resulting [1,2,3]triazolo[1,5-d][1,2,4]triazines displays a particular sensitivity due to the electron attracting effect of the triazole ring. Some mechanistic considerations are proposed to account for the observed results.     

On triazoles. XII. The carbamoylation and thiocarbamoylation of 5-amino-1,2,4-triazoles

The reaction of 5-amino-3-R-1H-1,2,4-triazoles 1 with isocyanates 2 (X = O) and isothiocyanates 2 (X = S) was studied. It was stated that with isocyanates 3a (X = O) type ring-carbamoylated products were formed which did not rearrange to the corresponding exo-carbamoylated derivatives 6a (X = O). On the other hand the thiocarbamoylation of derivatives 1 provided at mild conditions lead to derivatives 3a (X = S) which could be rearranged by heating to derivatives 6a (X = S). In one case the isomeric 4a (X = S) type derivative was also isolated. The comparison of the ir, uv, pmr and cmr spectra of the isomers isolated with the corresponding spectra of the carbamoylated and thiocarbamoylated 3,5-diamino-1,2,4-triazole derivatives helped to prove unequivocally the isomeric and tautomeric structure of compounds obtained giving a possibility to correct many confusions in the literature.     

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     

On triazoles XXX. Synthesis of [1,2,4]triazolo-[1,5-d][1,2,4,6]tetrazepine-5-thiones

Different 2-Q-6,7,8,9-(bi-, tri- or tetra)substituted[1,2,4]triazolo[1,5-d][1,2,4,6]tetrazepine-5-triione derivatives representing a novel ring system were synthesised. In the case of 8-aryl-substituted derivatives ring-chain tautomerism was observed in DMSO-d₆ or deuteriochloroform solutions. In some cases both ring and chain tautomers could be isolated in crystalline form. The structure of products obtained was proved by nmr using also model compounds prepared for this purpose.     

Dimroth rearrangement in the row of new pyrano[3,4-c][1,2,4]triazolo[4,3-a][1,5-a]pyridines and synthesis of new heterocyclic systems: Pyranopyrazolo[4,3-e][1,2,4]triazolopyridines

New and effective methods for the synthesis of derivatives of pyrano[3,4-c][1,2,4]triazolo[4,3-a][1,5-a]pyridines were developed. Synthesized new tetracyclic heterocyclic systems containing pyrano[3,4-c]pyridine ring unknown in the literature were obtained for the first time. The rearrangement of Dimroth in the triazolo[4,3-a]pyridine systems for the first time was studied. The possibility of rearrangement of Dimroth in the new heterocyclic system has been investigated.     

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,reactions, and antimicrobial activity of some novel pyrazolo[3,4-d]pyrimidine,pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,and pyrazolo[4,3-e][1,2,4]triazolo[3,4-c]pyrimidine derivatives

Treatment of N-phenyl-substituted benzenecarbo-hydrazonoyl chlorides 1a - d with malononitrile in sodium ethoxide solution gave 5-amino-4-cyanopyrazole derivatives 2 - 5 . Compounds 2 - 5 were converted to formidate derivatives 6 - 9 upon treatment with TEOF in acetic anhydride. The reaction of the latter products 6 - 9 with hydrazine hydrate gave imino-amino derivatives 10 - 13 , which was converted to hydrazino derivatives 14 - 17 by refluxing with hydrazine hydrate. Hydrazino as well as imino-amino derivatives undergo condensation, cyclization, and cycloaddition reactions to give pyrazolo[3,4-d]pyrimidine 18 - 21 , pyrazolo[4,3-e][1,2,4]triazolo-[3,4-c]pyrimidine 22 - 27 , and pyrazolo[3′,4′:4,5]pyrimido[1,6-b][1,2,4]triazine 42 - 44 derivatives. Antimicrobial studies are performed using two Gram-positive bacteria and two Gram-negative bacteria. Data indicated that compounds 5 , 28D , 29B , and 31D are exploring elevated antibacterial effects against all strains tested. Compound 28D is the most promising antibacterial agent against the delicate bacterial strain Bacillus subtilis and Pseudomonas aeruginosa with high effectiveness (low minimum inhibitory concentration [MIC] value) 40 and 60 μg/mL, respectively.     

Synthesis of triazolo[4,3-d], tetrazolo[1,5-a] -and quinazolino[3,2-d] [1,4] benzodiazepines

Treatment of 5-methylmercapto-1,4-benzodiazepine (I) with hydrazine hydrate gave the 5-hydrazino derivative (II, R = H) which, in turn, was conveniently cyclized to the title compounds. Another method for the synthesis of triazolo [4,3-d] [1,4] benzodiazepines (III) is also described.     

Efficient synthesis and In Silico study of some novel pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine derivatives

A novel series of 1,5-dihydropyrido-triazolo-pyrimidine derivatives were prepared by cyclocondensation of 2-thioxo-pyrido[2,3-d]pyrimidines (prepared from reaction of chalcone with 6-aminothiouracil) with a variety of hydrazonoyl chlorides. Based on spectroscopic evidence and their chemical syntheses, the structures of the newly prepared compounds were elucidated. Designated compounds are forced for molecular docking by using MOE 2014.010 Package software; one of in silico study tools. Synthesized compounds are targeting Human Cyclin-defendant Kinase 2 (CK2) PDB ID (1PXO.Protein data bank) due to its important role in controlling the human cell cycle and also for meiosis.     

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.     

Thermolysis of [1,2,4]triazolo[1,5-a]pyrimidine n-ylides

5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidinio-3-phenacylide ($\text{3}$) generated by the reaction of an iminium salt ($\text{2}$) with 1 eq. of triethylamine, underwent a new thermal ring cleavage of the triazole moiety to give the pyrimidine derivative. However reaction of $\text{2}$ with 2 eq. of triethylamine afforded the 2-iminooxazoline derivative. The iminooxazoline reacted with nucleophiles such as alcohols or amines to give imidazoles.     

New Facile Route to Synthesize Furo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine and Furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine Derivatives

A new facile route for synthesis of 3-(aryl)-8,9-diphenylfuro[3,2-e][1,2,4]triazolo pyrimidines derivative from the same starting material, 2-amino-4,5-diphenylfuran-3-carbonitrile, has been developed through heterocyclization of the corresponding arylidene-hydrazono-5,6-diphenylfuro[2,3-d]pyrimidine and N-(arylmethylene)-4-imino-5,6-diphenylfuro[2,3-d]pyrimidin-3(4H)-amine under refluxing condition with acetic anhydride followed by air oxidation. The products were obtained in good yield with an easy workup along with the purification of products by a nonchromatographic method. This general synthetic procedure can be extended to the preparation of a wide range of isomeric triazoles using 2-amino 3-carbonitrile bifunctional derivatives.