One-pot synthesis of imidazo[1,2-b]pyrazole,imidazo[1,2-b]-1,2,4-triazole,imidazo[1,2-a]pyridine,imidazo[1,2-a]pyrimidine,imidazo[1,2-a]benzimidazole,and 1,2,4-triazolo[4,3-a]benzimidazole derivatives

Hydrazonoyl bromides 1a-c react with 5-amino-3-phenyl-1H-pyrazole, 5-amino-1H-1,2,4-triazole, 2-aminopyridine, and 2-aminobenzimidazole to afford the corresponding imidazol[1,2-b]pyrazoles 10, imidazo[1,2-b]-1,2,4-triazoles 11, imidazo[1,2-a]pyridines 16, imidazo[1,2-a]pyrimidines 17, and imidazo[1,2-a]benzimidazoles 20, respectively. Compounds 1a-c reacted also with 2-methylthiobenzimidazole to give 1,2,4-triazolo[4,3-a]benzimidazole derivatives 21. © 1997 John Wiley & Sons, Inc.     

1,2,3-Triazolo[4,5-d]-1,2,4-triazolo[4,3-b]pyridazines

Some new 1,2,3-triazolo[4,5-d]-1,2,4-triazolo[4,3-b]pyridazines were prepared starting from the corresponding 1,2,3-triazolo[4,5-d]pyridazines via the formation of the 1,2,4-triazole ring, by condensation of an appropriate monocarbon fragment with the 4-hydrazino substituent and the nitrogen atom in the 5 position of the heterocycle. Condensation of 4-phenylhydrazino substituted derivatives with formic acid gave zwitterionic compounds.     

Preparation of new nitrogen-bridged heterocycles 72. A new approach to 1-acyl-3-(substituted methylthio)thieno[3',4':4,5]imidazo[1,2-a]pyridine derivatives. [corrected

The alkaline treatment of the pyridinium salts, readily available from the S-alkylations of 3-amino-4-(1-pyridinio)thiophene-5-thiolates with various alkyl halides, in chloroform at room temperature afforded the corresponding thieno[3',4':4,5]imidazo[1,2-a]pyridine derivatives in low to moderate yields via the intramolecular cyclization of the resulting 1,5-dipoles followed by the aromatization of the primary cycloadducts. Interestingly, the reactions using unsymmetrical 3-amino-4-[1-(3-methylpyridinio)]thiophene-5-thiolates afforded only 8-methylthieno[3',4':4,5]imidazo[1,2-a]pyridines and the other 6-methyl derivatives were not formed at all. In addition the isolation of a byproduct in the condensation reaction of pyridinium salt with the solvent (CHCl?) is also discussed.     

Synthesis of New 2-[(Substituted-pyrazolin-1-yl)carbonyl]-thieno[2,3-b]pyridine Derivatives

The reaction of 3-amino-4,6-dimethyl-2-thieno[2,3-b]pyridine carbohydrazide ( 1 ) with appropriate chalcones 2a-2d in the presence of acid catalyst produced the corresponding 3-amino-2-[(3,5-disubstituted-pyrazolin-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 3a-3d . 3-Amino-2-[(3-substituted-pyrazolin-1-yl)carbonyl]-4,6-dimethylthieno[2,3-b]pyridines 7a, 7b were also obtained by the cyclization reaction of carbohydrazide 1 with Mannich base derivatives 6a, 6b under basic condition.     

Synthesis of aromatic pyrazolo[4,5-b]pyridine derivatives

Cyclocondensation of chalcones with 5-amino-3-methyl-1-phenylpyrazole leads to the formation of 2,4-diaryl-5-methyl-7-phenyl-3,4-dihydropyrazolo-[4,5-b]pyridines, which undergo aromatization upon treatment with N-bromosuccinimide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1247–1251, September, 1987.     

Synthesis of substituted [1,3]thiazolo[4,5-b]pyridines and [1,3]thiazolo[4,5-d][1,2,3]triazines

In this work, we described an easy preparation of substituted 4-amino-5-cyano-1,3-thiazoles. These compounds have been used as starting materials to obtain two classes of compounds. New substituted [1,3]thiazolo[4,5-e]pyridines were synthesized in one step via Friedländer reaction. Diazotation of 4-amino-5-cyano-1,3-thiazoles afforded 4-chloro[1,3]thiazolo[4,5-d][1,2,3]triazines in one step. The later was substituted by a secondary amine to obtain substituted 4-amino[1,3]thiazolo[4,5-d][1,2,3]triazines.     

An Improved Synthesis of 3-Substituted 1,2,4-Triazolo[4,3-a]pyridines and 1,2,4-Triazolo[4,3-b]pyridazines

The preliminary results of a simple and versatile one-pot procedure for the preparation of 3-substituted 1,2,4-triazolo[4,3-a] pyridines and 1,2,4-triazolo[4,3-b]pyridazines are described. Intramolecular cyclization of nitrile imine ylides are carried out by treatment of 2-pyridyl- and 3-pyridazinylhydrazones with chloramine T.     

Synthesis of derivatives of 5-amino-4-acyl-1,2,3-triazole, 8-azapurine,and 1,2,3-triazolo[4,5-b]pyridin-7-one using N,N-acetals of acylketenes and tosylazide

By reaction of N,N-acetals of acylketenes with tosylazide there were synthesized 5-amino-4-acyl-1,2,3-triazoles substituted at the endo(N¹)- or exocyclic nitrogen atom. Triazoles containing a free NH₂ group were used in the synthesis of the corresponding 8-azapurines and 4-acetyl-5-benzoylamino-1,2,3-triazole afforded 2-methyl-2H,4H-1,2,3-triazolo[4,5-b]pyridin-7-one.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 6, pp. 1392–1397, June, 1990.     

Synthesis of thiopyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines

<正>Reactions of the 6-hydroxy-thiopyrano[3,4-c]pyridine-5-carbonitrile derivative 1 withα-halo-carbonyl compounds gave the ortho-substituted intermediates 2a-c which were converted into furo[2,3-b]thiopyrano[4,3-d]pyridines 3a-c by fusion of a furan moiety under basic conditions.Further cyclization of 3a-c led to a fusion of a pyrimidine ring,yielding the tetracyclic products 6,7 and 8.In addition,condensation of 6 with various aromatic aldehydes afforded the corresponding imines 9a,b.Mannich reaction of 7 gave products 10a,b.     

Chemistry of furazano[3,4-b]pyrazine 6. 1,2,3-triazolo[4,5-b]furazano[3,4-b]pyrazines

The reduction of 1,2,3-triazolo[4,5-e]furazano[3,4-b]pyrazine 6-oxide was investigated. By means of data from x-ray crystallographic analysis it was shown that there is a relation between the aromaticity and the structure of the obtained triazoles.For communication 5, see [1].Latvian Institute of Organic Synthesis, Riga LV-1006. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1259–1264, September, 1998.     

Transformation of 3,4-bis(formylamino)pyridine into 4-nitro-1,2,3-triazolo[4,5-<Emphasis Type="Italic">c</Emphasis>]pyridine 2-oxide in the reaction with nitrating mixture

Treatment of 3,4-bis(formylamino)pyridine with a mixture of concentrated nitric and sulfuric acids unexpectedly afforded 4-nitro-1,2,3-triazolo[4,5-c]pyridine 2-oxide. Reduction of the latter with iron in acetic acid gave previously known 4-amino-1,2,3-triazolo[4,5-c]pyridine.Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 10, 2004, pp. 1574–1575.Original Russian Text Copyright © 2004 by Yutilov, Smolyar.     

Reduction of Imidazo[4,5-c]pyridine and [1,2,3]Triazolo[4,5-c]pyridine Derivatives to Spinaceamines and 2-Azaspinaceamines

Reduction of 1-substituted [1,2,3]triazolo[4,5-c]pyridines with nickel-aluminum alloy in aqueous alkali gave 2-azaspinaceamines. Reduction of imidazo[4,5-c]pyridine and [1,2,3]triazolo[4,5-c]pyridine derivatives with formic acid in the presence of triethylamine resulted in formation of 5-formylspinaceamines and 2-azaspinaceamines. The 5-formyl group in the latter can be removed by acid hydrolysis. Unsubstituted 2-azaspinaceamine, an aza analog of natural spinaceamine, was synthesized for the first time.     

Syntheses of 3-[5-Methyl-1-(4-Methylphenyl)-1,2,3-Triazol-4-yl]-6-Substituted-s-Triazolo[3,4-b]-1,3,4-Thiadiazoles

1,2,3-Triazole derivatives have been reported as inhibiting tumor proliferation, invasion, and metastasis^[1]. The fused l,3,4-triazolo[3,4-b]-1,3,4-thiadiazoles derivatives show various biological effects such as antifungal^[2], antibacterial, hypotensive and CNS depressant activities^[3]. We have reported several 6-aryl-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[3,4-b]-1,3,4-thiadiazoles in the previous paper^[4]. The novel 6-aryl-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazolo[2,4-b]-1,3,4-thiadiazoles 6a-j have been synthesized by the condensation of 4-amino-5-mercapto-3-[5-methyl-1-(4-methylphenyl)-1,2,3-triazol-4-yl]-s-triazole 5 with various aromatic carboxylic acids in the presence of phosphorus oxychloride. The mercaptotriazole 5 was prepared from 4,the latter being prepared from 1 throng 2 and 3. The title compounds 6 were depicted in scheme 1. The structures of these compounds were established by elemental analysis, NMR, MS and IR techniques.     

C- and N-alkylation of 4,5-dihydro-1H-indeno[1, 2-b]pyridine derivatives

2-Methyl-4-aryl-5-oxo-4,5-dihydro-1H-indeno[1,2-b]pyridine derivatives react with methyl iodide in an aprotic medium in the presence of alkaline agents to give C- and N-alkylation products, viz., 2,4a-dimethyl- and 1,2-dimethyl-4-aryl-5-oxo-4,5-dihydroindeno[1,2-b]pyridines, and with dimethyl sulfate or methyl p-tosylate under the same conditions to give N-methylation products.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 393–398, March, 1984.     

Annulated 1,2,3-triazoles. 3. Synthesis of 1,2,3-triazolo[4,5-b][1,5]benzoxazepin-10(9H)-ones and 10-(4-substituted-1-piperazinyl)-1,2,3-triazolo[4,5-b][1,5]benzoxazepines

10-(4-Substituted-1-piperazinyl)-1,2,3-triazolo[4,5-b][1,5]benzoxazepines 11 were prepared in a three-step synthesis starting from easily available 5-chloro-1,2,3-triazole-4-carbonyl chlorides 7 by titanium tetrachloride catalyzed condensation of N-(substituted)piperazines with 1,2,3-triazolo[4,5-b][1,5]benzoxazepin-10(9H)-ones 10 formed by ring closure of the intermediate amides 9 . Although lactams 10 were obtained as the sole product of the cyclisation at 80°, the unexpected by-products 13 and 14 were formed in addition to 10c at 150° from 9c . The 4-methoxybenzyl group in 11j was easily removed by solvolyses in TFA. Compounds 11d-f and 11i were tested for psychotropic activity.     

Syntheses of Oxazolo [4,5-b]pyridines and [4,5-d]pyrimidines

Oxazolo [4, 5-b] pyridines and [4, 5-d] pyrimidines and their 2-substituted compounds have been prepared respectively by condensation of orthoesters or thioimidates derivatives with 2-amino-3-hydroxypyridine and 4-amino-5-hydroxypyrimidine.     

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).     

Synthesis of 1,2,3-triazolo[1,5-a]pyridine ester derivatives

Lithiation of 1,2,3-triazolo[1,5-a]pyridines 4b and 4c with lithium diisopropylamide (LDA) gave the corresponding lithio derivatives 5b and 5c from which esters 6b and 6c were obtained by treatment with carbon dioxide and then dimethyl sulfate. Lithio derivatives 5a-5c reacted with DMF giving aldehydes 7a-7c. Esters 9a-9c were prepared from aldehydes 7a-7c and carbomethoxymethylenetriphenylphosphorane.     

Convenient synthesis and anticancer evaluation of novel pyrazolyl-thiophene,thieno[3,2-b]pyridine,pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine derivatives

The newly synthesized 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was utilized as a precursor for the synthesis of pyrazolyl-thiophene derivative, which undergoes cyclization upon treatment with benzaldehyde derivatives to provide pyrazolo[3,4-d]thieno[3,2-b]pyridines. Basic treatment of pyrazolyl-thiophene derivative with phenyl isothiocyanate followed by subsequent addition of chloroacetone and/or ethyl bromoacetate yielded the thiazolylidene-pyrazolyl thiophenes. In addition, the building block 3-(3-amino-5-(phenylamino)-4-(phenylcarbamoyl)thiophen-2-yl)-3-oxopropanoate was converted into the corresponding thieno[3,2-b]pyridine compounds through its reactions with (DMF-DMA) and/or heating in sodium ethoxide. Moreover, the reaction of 7-hydroxy-5-oxo-N-phenyl-2-(phenylamino)-4,5-dihydrothieno[3,2-b]pyridine-3-carboxamide with 2-arylidenemalononitrile produced the new annulated pyrano[2,3-d]thieno[3,2-b]pyridines. The prepared thiophene-based compounds were evaluated against HepG2, PC3, and MCF-7 cancer cells, and normal fibroblast cell (WI38). The pyrazolo[3,4-d]thieno[3,2-b]pyridine and pyrano[2,3-d]thieno[3,2-b]pyridine compounds substituted with chlorophenyl group presented promising cytotoxic activities against HepG2 cancer cell line without any human toxicity. Docking study for the synthesized thiophene compounds delivered valuable insights about the binding interactions with the crystal structure of NS5B enzyme with PDB ID (4TLR).     

Synthesis and electrochemical properties of 2,6-bis（6-aryl-[1,2,4]- triazolo[3,4-b][1,3,4]-thiadiazole-3-yl）pyridines

By the condensation of 2,6-bis（4-amino-5-mercapto-[1,2,4]-triazoles-2）pyridine with aromatic acid in the presence of phosphorus oxychloride. Compounds of 2,6-bis（6-aryl-[1,2,4]-triazolo[3,4-b][1,3,4]-thiadiazole-3-yl）pyridines were synthesized. Their structures were confirmed by IR, ^1H NMR spectroscopies and elemental analysis. Their electrochemical behavior and cyclic voltammogram also were be studied. The results showed that they have high ionization potentials and good affinity.