Synthesis and nitration of NH- and N-vinyl-4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridines

It has been shown that the most efficient catalysts for the synthesis of 4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine from 1,2,5-trimethylpyridin-4-one and acetylene under Trofimov conditions are rubidium and potassium hydroxides. Use of Triton B or a mixture of trimethylbenzylammonium chloride with rubidium hydroxide as catalyst gives O-alkylated oxime. Their configurations and conformations were established through separation of the individual isomers of 1-vinyl-4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridines. Acetyl nitrate nitration of the cis isomer of this compound gave the 2- and 3-nitro derivatives. Similar nitration of 4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine gave the 2-nitro-7-hydroxy derivative.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1375–1380, October, 1991.     

Synthesis of 2-R-4,5,7-trimethyl-1-vinyl-4,5,6,7-tetrahydropyrrolo[3,2-<Emphasis Type="Italic">c</Emphasis>]pyridines

The synthesis of 1-vinyltetrahydropyrrolo[3,2-c]pyridines substituted at C₍₂₎ has been accomplished, based on 4,5,7-trimethyl-1-vinyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine and its 2-formyl-substituted derivative.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, 1709–1716, November, 2004.     

Study of the stereochemistry of N-H and N-vinyl-4,5,7-trimethyi-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridines and their nitro derivatives by the method of 1H and 13C NMR

The configurations and conformational features of N-H and N-vinyl-4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridines and their nitro derivatives were established by the method of ¹H and ¹³C NMR spectroscopy. It was shown that the conformational uniformity of the piperideine ring in the compounds studied is strongly dependent on the character of the substituents in the pyrrole ring. A method for the determination of the orientation of the substituent at the -position to the nitrogen atom of the piperideine ring, according to the direct ¹J_CH SSCC, was proposed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 75–81, January, 1993.     

Synthesis and pharmacological evaluation of 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine derivatives as platelet aggregation inhibitors

One pot synthesis and characterization of new 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridines (3a–k) using amides (2a–k) were reported. The prepared 5-[2′-(1H-tetrazol-5-yl)-biphenyl-4-ylmethyl]-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine (3a) is a bioisostere of 4′-(6,7-dihydro-4H-thieno [3,2-c]pyridin-5-ylmethyl)-biphenyl-2-carboxylic acid (1), having good in vivo antithrombotic activity compared with Clopidogrel. The new tetrazole derivatives (3a–k) were screened for their in vitro activity as platelet aggregation inhibitors.     

Lactams of acetals and acid amides, 45. Synthesis of condensed 2-pyridones from activated amides,lactams, and lactones

By reaction of lactim ethers with N-substituted cyanoacetamides, the corresponding enaminoamides were obtained, cyclization of which by dimethylformamide acetal gave derivatives of pyrrolo[3,2-c]pyridine, 1,6-naphthyridine, and pyrido[4,3-b]azepine, having a substituent at the nitrogen atom of the pyridone ring. N-substituted furo[3,2-c]pyridines were synthesized from the diethyl acetals of butyrolactone and 3-(dimethylaminomethylene)butyrolactone and dimethylformamide acetal.For communication 44, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 929–932, July, 1985.     

Ring closure of some O-aryl ethers of ketoximes to benzofurans

The action of alcohol solutions of hydrogen chloride on aryl ethers of the oximes of N-substituted 4-piperidones (Ia-c) yielded rearrangement products — 3-(2-hydroxyaryl)-4-piperidones (IIa, b) and (or) 4a-aikoxy-l,2,3,4,4a,9b-hexahydrobenzofuro[3,2-c]pyridines (IIIa-c), which, under certain conditions, are readily converted to 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridines (IVa, b). Ketones of the II type are ketalized to dihydrobenzofurans III by alcohol solutions of hydrogen chloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1596–1600, December, 1971.     

Nouvelles voies d'accès à des aryl-4 thiéno[2,3-c]pyridines et à des aryl-7 thiéno[3,2-c]pyridines

4-Arylthieno[2,3-c]pyridines and 7-arylthieno[3,2-c]pyridines have been prepared by heating in polyphosphoric acid 2-(2-thenylamino>l-arylethanols or propanols and 2- 3-thenylamino>l-arylethanols or propanols, respectively.) Under the Beckmann rearrangement conditions, oximes of 4-aryl-4,5-dihydro-6H-cyclopenta[b]thiophen-6-one lead to 4-aryl-4,5- dihydro-6H-thieno[2,3-c]pyridin-7-one.     

Mesoionic compounds with a bridged nitrogen atom.

The cyclization of (4-quinazolinylthio)phenylacetic and acetic acids gives extremely reactive thiazolo[3,2-c]quinazolinium 3-oxides, which, depending on the structure of the mesoionic ring, react with either electrophilic or nucleophilic reagents.See [1] for Communication 16.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 408–412, March, 1989.     

Transformations of 2-trifluoroacetyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridines by the action of ethyl propynoate. A novel synthesis of 2-trifluoroacetyl-4,7,8,9-tetrahydro-1H-pyrrolo[2,3-d]azocines

2-Trifluoroacetyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridines reacted with ethyl propynoate in acetonitrile and methanol to give ethyl 2-trifluoroaceyl-4,7,8,9-tetrahydro-1H-pyrrolo[2,3-d]azocine-5-carboxylates. The reactions of 2-trifluoroacetyl-1-vinyl-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridines with ethyl propynoate in alcohols were accompanied by cleavage of the tetrahydropyridine fragment with formation of alkyl 3-{benzyl[2-(3-alkoxy-5-trifluoroacetyl-1-vinyl-1H-pyrrol-2-yl)ethyl]amino}acrylates.     

The stereochemistry of the protonated forms of heterocyclic bases

The configurational and conformational ratios of protonated 2,4-dimethyl- and 1,2,4-trimethyl-1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridines and their conjugate bases were studied by PMR spectroscopy. The trimethyl derivatives have a 1,4-trans configuration. The equilibrium concentrations of the epimeric salts in solution were determined. In the crystalline state the salts exist in the form of the energetically more favorable epimer, which in solution has a completely equatorial conformation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1081–1086, August, 1978.     

Halogenation of 2-Unsubstituted and 2-Methylimidazo[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridine Derivatives

Halogenation of 2-unsubstituted and 2-methylimidazo[4,5-b]pyridines and their N-methyl derivatives with bromine and chlorine in acetic acid takes different pathways, depending on the acetic acid concentration. The bromination in 50% aqueous acetic acid gives only 6-bromoimidazo[4,5-b]pyridines; bromination and chlorination of 2-unsubstituted imidazo[4,5-b]pyridines in glacial acetic acid leads to 5,6-dibromo(dichloro)imidazo[4,5-b]pyridin-2-ones, and bromination of 2-methylimidazo[4,5-b]pyridines in glacial acetic acid involves both the pyridine ring and the 2-methyl group to afford the corresponding 6-bromo-2-tribromomethylimidazo[4,5-b]pyridines.__________Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 3, 2005, pp. 457–461.Original Russian Text Copyright © 2005 by Yutilov, Lopatinskaya, Smolyar, Gres’ko.     

Synthesis of polysubstituted 4,5,6,7-tetrahydrofuro[2,3-c]pyridines by a novel multicomponent reaction

[reaction: see text] A novel three-component synthesis of tetrahydrofuro[2,3-c]pyridines from readily accessible starting materials is described. Simply heating a toluene solution of an aminopentynoate, an aldehyde, and an alpha-isocyanoacetamide in the presence of ammonium chloride provided the 4,5,6,7-tetrahydrofuro[2,3-c]pyridines in good to excellent yield. The fused ring system is produced in this one-pot process by the concomitant formation of five chemical bonds.     

Ring contraction of thia(seleno)diazine rings into pyrazoles in the reaction of 3-aryl-10-methyl-2H-1,3,4-thia(seleno)diazino[3, 2-a]benzimidazolium salts with bases

Reaction of 3-aryl-10-methyl-2H-1,3,4-thiadiazino[3,2-a]benzimidazolium salts with triethylamine led to ring contraction of the thiadiazine ring to a pyrazole ring with the formation of a mixture of derivatives of 3-mercaptopyrazolobenzimidazole and di(pyrazolo[1,5-a]benzimidazolyl-3) disulfide. The disulfides were formed exclusively when these salts react with ethanolic alkali. The reaction with potassium carbonate in acetic anhydridegave3-acetylthiopyrazolo[1,5- a]benzimidazoles. 2-Aryl-4- alkylpyrazolo[1, 5- a]benzimidazoles were formed by heating thiadiazino[3,2-a]benzimidazolium salts in formamide and by treating selenodiazino[3,2-a]benzimidazolium salts with potassium carbonate in acetic anhydride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1698–1705, 1992.     

Chemical reactions of 4,5,6,7-tetrahydro-4,5,7-trimethylpyrrolo[3,2-c]pyridine and its 2-formyl derivative

N-Alkyl substituted tetrahydropyrrolo[3,2-c]pyridines have been obtained by alkylation of 4,5,6,7-tetrahydro-4,-5, 7-trimethylpyrrolo[3,2-c]pyridine and its 2-formyl derivative chloroalkyldimethylamines, acrylonitrile, methyl acetylenedicarboxylate and dichloroethane. 2-Formyl substituted tetrahydropyrrolo[3,2-c]pyridine has been reduced with sodium borohydride and condensed with monoethanolamine and hydroxylamine. The stereochemistry of the products has been studied by ¹H NMR spectroscopy.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 681–687, May, 1993.     

Synthesis and recyclization of 6-benzyl-3a,4,5,6,7,7a-hexahydro-3a-hydroxy-7a-methyl-2-thioxo-5-phenyloxazolo[5,4-c]pyridines

The corresponding oxazolo[5,4-c]pyridines were obtained in the reaction of stereoisomeric 1-benzyl-3-hydroxy-3-methyl-6-phenyl-4-piperidines with potassium thiocyanate in acetic acid and rearranged into 6-benzyl-5,6,7,8-tetrahydro-1-methyl-3-thioxo-7-phenyloxazolo[3,4-c]pyrimidine by boiling in o-xylene. It was shown that the rearrangement is reversible.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1262–1265, September, 1992.     

Dakin-West trick in the design of novel 2-alkyl(aralkyl) derivatives of oxazolo[3,2-a]pyridines

A series of previously unavailable derivatives of 2-alkyl- and 2-benzylderivatives of oxazolo[3,2-a]pyridines III were obtained via tandem ring opening and ring closure from stable mesoionic 3-acyloxazolo[3,2-a]pyridinium-2-olates I. The key intermediates of this tandem transformation are N-(b-oxoethyl)pyridones-2 II obtained by Dakin-West acylation of (pyridone-2-yl-1)acetic acid. An example of further utilization of this strategy is illustrated by preparation of unknown 2-benzylimidazo[1,2-a]pyridine from the salt I and ammonia.     

Synthesis of pyrylium and pyridine derivatives of benzofuran

Acylation of benzo[b]-2-furyl acetone was used to synthesize 2,9-disubstituted benzofuro[3,2c] pyrylium perchlorates, which were converted in high yields to the corresponding benzofuro-[3,2-c]pyridines. The molecular diagram of the pyrylium cation is examined. The IR, UV, and NMR spectra of the synthesized compounds are discussed.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 450–456, April, 1973.     

Nouvelle méthode d'accès aux benzo[h]furo[3,2-c]quinoléines,analogues isostériques des benzo[c]phénanthridines

A convenient synthesis of the benzo[h]furo[3,2-c]quinoline ring is reported. Hydrogenation of dienic adducts 5 gives comppounds 6. Successive pyrolysis and alcaline hydrolysis of 6 provide diacids 9 which in the presence of anhydrous ammonium acetate and acetic acid undergoes intramolecular cyclisation to give benzo[h]furo[3,2-c]quinolone derivatives 12. The modulation of the 7-carboxy group and introduction of amino groups in the 6 position are then realized.     

One-pot synthesis of 3-(sulfonyl)-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridines through a cascade Michael/cyclization reaction

In this paper, a straightforward and valid three-component Michael/cyclization reaction of (E)-1-methyl-3-(arylidene)piperidin-4-ones, 2-(sulfonyl)acetonitriles, and aromatic aldehydes was explored for the preparation of potentially biologically active 3-(sulfonyl)-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridines under mild reaction conditions. More diverse 3-(sulfonyl)-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridine derivatives were constructed in satisfactory yields (up to 97%). The chemical structure of newly synthesized 3-(sulfonyl)-5,6,7,8-tetrahydro-4H-pyrano[3,2-c]pyridines were identified with ¹H-NMR, ¹³C-NMR, and mass spectrometry analysis. The recommendable method features a simple and direct workup, easy access to initial materials, high atom utilization efficiency, high final product yields, and a wide range of substrate adaptability.     

Tetracyanoethylation and fischer rearrangement of some 4-oxo-4,5,6,7-tetrahydroindoles

The reaction of the 1,2-diaryl-4-oxo-4,5,6,7-tetrahydroindoles, and 3-methyl-4-oxo-4,5,6,7-tetrahydroindole with tetracyanoethylene occurred at the 5 position of the tetrahydroindole ring. A Fischer rearrangement of the phenylhydrazones of these 4-oxotetrahydroindoles gave pyrrolo [2,3-c]carbazoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 217–221, February, 1986.