Synthesis of furo[3,2-c]pyridine and furo[2,3-d]pyrimidine derivatives from butyrolactone diethylacetal

The reaction of butyrolactone acetal with CH acids was used to synthesize 2-methylenetetrahydrofuran derivatives. The latter react with dimethylformimide acetal to give a dieneamine that is capable of undergoing cyclization to furo [3,2-c]pyrimidine derivatives. This two-ring system was also synthesized by the reaction of cyanacetamide with 3-dimethylaminomethylenebutyrolactone acetal. The indicated acetal can also react with amidine components to give furo [2,3-d]pyrimidine derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 68–71, January, 1982.     

Acetals of lactams and acid amides. 35. Synthesis of condensed two- and three-ring pyridine systems on the basis of enamino amides

The synthesis of 2,3,5,6-tetrahydropyrrolo[3,2-c]pyrid-6-one was accomplished by rearrangement of 8H,1-cyano-8-dimethylaminomethylene-2,5,6,7-tetrahydropyrrolo[1, 2-c]pyrimidine. Pyrrolo[3,2-c]pyrimidine, 1,6-naphthyridine, and pyrimido[4,3-b]-azepine derivatives were synthesized on the basis of enamino dinitriles. The hydrolysis of 8H,1-cyano-8-dimethylaminomethylene-2,5,6,7-tetrahydropyrrolo[1,2-c]-pyrimidine in 50% CH₃COOH leads to a pyrrolo[1,2-c]pyrido[4,3-d]pyrimidine derivative. A similar dipyrido[4,3-d-1,2-c]pyrimidine derivative was obtained from 1-cyano-9-dimethylaminomethylene-2,5,6,7,8,9-hexahydropyrido[1,2-c]pyrimidine under these conditions, and 3,4-dioxo-3,4,7,8,9,10-hexahydropyrido[1,2-c]pyrano[4,3-d]-pyrimidine was synthesized bytreatment with a 1 N solution of HCl.See [1] for Communication 34.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 518–522, April, 1982.     

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.     

Nucleophilic displacement of aromatic fluorine,Part III,indoloquinolines and benzofuranoquinolines

Variously substituted indolo[2,3-c]quinolines, benzofurano[2,3-c]quinolines and their positional isomers indolo[3,2-c]quinolines and benzofurano[3,2-c]quinolines respectively, were prepared from both indole and quinoline derivatives by intramolecular nucleophilic displacement of aromatic fluorine. The formation of an indolo[2,3-d]benzazepine was also observed.     

Acetals of lactams and acid amides. 33. Reaction of secondary enamino amides with amide acetals and synthesis of condensed pyrimidines

Condensed pyrimidines were synthesized by the reaction of dimethylformamide and dimethylacetamide diethylacetals with secondary enamino amides. It is shown that the piperido[1,2-c]pyrimidine derivative undergoes rearrangement to a 1,6-naphthyridine derivative under mild conditions.See [1] for communication 32.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1120–1124, August, 1980.     

Acetals of lactams and acid amides. 34. Synthesis and properties of enamines of the isoquinoline series

The reactions of 1,2,3,4-tetrahydro-3-isoquinolone derivatives with dimethylformamide acetal and the hydrolysis and transamination of the resulting enamino amides — 1,2,3,4-tetrahydro-4-dimethylaminomethylene-3-isoquinolone derivatives — were studied. It is shown that 1,2,3,4-tetrahydro-1-phenyl-6,7-dimethoxy-3-isoquinolone can be converted to the corresponding lactim ether. The reactions of the latter with dimethylformamide acetal and hydrazine and the dehydrogenation of this lactim ether in the presence of sodium ethoxide were studied.See [1] for Communication 33.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 511–515, April, 1981.     

Acetals of lactams and acid amides

The reaction of dimethylformamide diethylacetal with -cyano--dimethylaminoacrylamide proceeds at the NH₂ amide group to give the corresponding acylformamidine, from which 3-cyano-4-dimethylamino-2-pyridone was obtained by thermal cyclization. Pyrrolo-, pyrido-, and azepino-[3,2-c]pyridine derivatives were similarly synthesized from 1-methyl-2-(2-cyano-2-carbamido)-methylenepyrrolidine and the homologous six- and seven-membered enaminoamides.See [1] for communication XVII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1509–1512, November, 1976.     

Heterocyclic quinones. XVI. Pharmacomodulation in the series of 11H-indolo[3,2-c]quinolinediones: synthesis, cytotoxicity and antitumor activity of 3-substituted 11H-pyrido[3',4':4,5]pyrrolo[3,2-c]quinoline-1,4-diones

With the aim of obtaining new antitumor drugs more active than previously described 11H-indolo[3,2-c]quinoline-1,4-diones and 7,8,9,10-tetrahydro-11H-indolo[3,2-c]quinoline-1,4-diones, the synthesis and activities of a series of 3-substituted 11H-pyrido[3',4':4,5]pyrrolo[3,2-c]quinoline-1,4-diones and of 7,8,9,10-tetrahydro-11H-pyrido-[3',4':4,5]pyrrolo[3,2-c] quinoline-1,4-diones were studied. Some quinones were more cytotoxic in vitro towards L1210 leukemia cells but were not active in vivo towards murine P388 leukemia.     

Sesquiterpenoid derivatives from Ferula ferulaeoides [correction of ferulioides]. V

Nine novel prenyl-dihydrofurocoumarin-type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-2-[4-methyl-5- (4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2R*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadienyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4,8-dimethyl-3(E),7-nonadien-6-onyl]-furo-[3,2-c]coumarin, and 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-2-[4-methyl-5-(4-methyl-2-furyl)-3(E)-pentenyl]-furo[3,2-c]coumarin, were isolated from the roots of Ferula ferulaeoides [corrected]. The structures were established by comprehensive spectral analysis. The biosynthetic pathway leading to these prenyl-furocoumarin-type sesquiterpenoids is proposed based on their structures.     

Heterocyclic quinones. XIV. Pharmacomodulation in a series of 11H-indolo[3,2-c]quinolinediones: synthesis and cytotoxicity of 8-substituted 11H-indolo[3,2-c]quinoline-7,10-diones

4-Chloro-8-methoxy-11H-indolo[3,2-c]quinoline could be obtained from 8-chloro-2,3-dihydro-1H-quinolin-4-one and 4-methoxyphenylhydrazine by applying Fischer's indole synthesis. Its nitration led to the 7-nitro derivative which was reduced to 7-amino-4-chloro-8-methoxy-11H-indolo[3,2-c]quinoline when Raney nickel was employed as a catalyst and to 7-amino-8-methoxy-11H-indolo[3,2-c]quinoline when palladium charcoal was used. Oxidation of the amines by potassium nitrosodisulfonate produced the corresponding 11H-indolo[3,2-c]quinoline-7,10-diones. Displacement of the methoxy group by (N,N-diethylamino)ethylamine or by N-methylpiperazine afforded the 8-aminoquinones. The quinones unsubstituted at the 4-position were more cytotoxic than the previously described 2-methoxy-11H-indolo[3,2-c]quinoline-1,4-diones.     

A new synthesis of benzofuro[3,2-c]pyridines

The condensation of O-phenylhydroxylamine with piperidin-4-one and 3-methylpiperidin-4-one has given 1,2,3,4-tetrahydrobenzofuro[3,2-c]pyridine and 4-methyl-1,2,3,4-tetrahydro-benzofuro [3,2-c]pyridine, and these have been dehydrogenated to the corresponding heteroaromatic system of benzofuro[3,2-c]pyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No.7, pp. 908–909, July, 1973.     

Five new peltogynoids from underground parts of Iris bungei: a Mongolian medicinal plant

Five new peltogynoids, irisoids A-E (1-5), have been isolated from the underground parts of Iris bungei. The structures of the new compounds were established on the basis of spectroscopic methods and were found to be 1,8,10-trihydroxy-9-methoxy-[1]benzopyrano-[3,2-c][2]-benzopyran-7(5H)-one (1), 1,8-dihydroxy-9,10-dimethoxy-[1]benzopyrano-[3,2-c][2]-benzopyran-7(5H)-one (2), 1,10-dihydroxy-8,9-dimethoxy-[1]benzopyrano-13,2-c][2]-benzopyran-7(5H)-one (3), 1,8-dihydroxy-9,10-methylenedioxy-[1]benzopyrano-[3,2-c][2]-benzopyran-7(5H)-one (4), and 1,8,11-trihydroxy-9,10-methylenedioxy-[1]benzopyrano-[3,2-c][2]-benzopyran-7(5H)-one (5). The structure of irisoid B (2) was established unambiguously by X-ray diffraction study.     

Interaction of 4,5,7-Trimethyl-4,5,6,7-tetrahydropyrrolo[3,2-<Emphasis Type="Italic">c</Emphasis>]pyridines with Acetic and Trifluoroacetic Anhydrides

The reactions of NH- and N-vinyl-4,5,7-trimethyl-4,5,6,7-tetrahydropyrrolo-[3,2-c]pyridines and their 2-substituted derivatives with acetic and trifluoroacetic anhydrides have been studied. Trifluoroacetylation of tetrahydropyrrolo-[3,2-c]pyridines occurs at the α-position of the pyrrole ring, whereas cleavage of the tetrahydropyridine ring with formation of 3-vinylpyrroles occurs with acetic anhydride. 2-Acetyl-4,5,7-trimethyl-1-vinyl-4,5,6,7-tetrahydropyrrolo[3,2-c]pyridine was synthesized by the Vilsmeier-Haack reaction.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, 751–760. May, 2005.     

Acetals of lactams and acid amides. 41. Enamino amides in the synthesis of pyrimidine derivatives

The reaction of -cyano--dimethylaminomethyleneacrylamide with arylamines was used to synthesize -cyano--arylaminoacrylamides, which react readily with dimethylformamide diethylacetal to give the corresponding N-dimethylaminomethylene derivatives. The latter undergo cyclization to 1-aryl-5-cyano-4-pyrimidinones when they are heated in dimethylformamide or acetic anhydride and to pyrimido-[5,4-c]quinolone derivatives when they are heated in glacial acetic acid.See [1] for communication 40.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 538–542, April, 1984.     

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.     

Sesquiterpenoid derivatives from Ferula ferulaeoides [correction of ferulioides]. IV

Four novel prenyl-furocoumarin type sesquiterpenoid derivatives, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-3-[4,8-dimethyl-3(E),7-nonadie nyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2R*,3R*-dimethyl-3-[4,8-dimethyl-3(E),7-nonadie nyl]-furo[3,2-c]coumarin, 2,3-dihydro-7-hydroxy-2S*,3R*-dimethyl-3-[4-methyl-5-(4-methyl-2-furyl)- 3(E)-pentenyl]-furo[3,2-c]coumarin, and 2,3-dihydro-7-methoxy-2S*,3R*-dimethyl-3-[4,8-dimethyl-3(E),7-nonadie nyl]-furo]3,2-c]coumarin were isolated from the roots of Ferula ferulaeoides [corrected]. Their structures were established by detailed spectral analysis and the biosynthetic pathway leading to these prenyl-furocoumarin type sesquiterpenoids is proposed based on these structures.     

The Piloty-Robinson reaction of N-substituted piperidin-4-one azines. A novel route for the synthesis of 3,6-diazacarbazole

The possibility of preparing 1,2,3,4,6,7,8,9-octahydro-5H-pyrrolo[3,2-c:4,5-c']dipyridines using the Piloty-Robinson reaction has been studied under various conditions. A novel method is proposed for the synthesis of the aromatic 3,6-diazacarbazole (5H-pyrrolo[3,2-c:4,5-c']dipyridine) from 2,8-dibenzoyl-1,2,3,4,6,7,8,9-octahydro-5H-pyrrolo[3,2-c:4,5-c']dipyridine obtained for the first time by the Piloty- Robinson method under thermal conditions.     

Condensed O-, N-heterocycles by the transformation of azidoacrylates

Summary A number of furo[3,2-c]pyridines (4a–4d) and benzo[b]derivative (4e), as well as pyrrolo[2,3-4,5]furo[3,2-c]pyridine (8) were prepared by reaction of the corresponding iminophosphoranes, available from ethyl azidoheteroacrylates and triphenylphosphine, with phenyl isocyanate. The appropriate azidoheteroacrylates were used for the preparation of some substituted furo[3,2-b:4,5-b]dipyrroles (6). The reactions of the prepared compounds are described.

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Kondensierte O-, N-Heterocyclen durch Umwandlung von Azidoacrylaten

Zusammenfassung Eine Anzahl von Furo[3,2-c]pyridinen (4a –4d), ein Benzo[b]derivat (4e) und Pyrrolo[2,3:4,5]furo[3,2-c]pyridin (8) wurden durch die Reaktion von Phenylisocyanaten mit den entsprechenden Iminophosphoranen dargestellt, die aus Ethyl-azidoheteroacrylaten und Triphenylphosphin leicht zugänglich sind. Die entsprechenden Azidoacrylate wurden zur Synthese einiger Furo[3,2-b:4,5-b]dipyrrole (6) verwendet. Die Reaktionen einiger dieser Verbindungen werden beschrieben.

     

Synthesis of new pyrrolo-[3,4-c]isoxazole, pyrrolo[2,3-d]-[1,2,3]triazole, triazolo[4,5-c]-pyridazine, and dipyrrolo-[3,2-b:3′,4′-d]pyran derivatives

New pyrrolo[3,4-c]isoxazole derivatives were synthesized from the key intermediates 4-cyanopyrrolidin-3-ones in two steps. Pyrrolo[2,3-d][1,2,3]triazoles and triazolo[4,5-c]pyridazine were obtained from 2-arylhydrazono-4-cyano-1-(4′-methoxyphenyl)-3-oxopyrrolidines by refluxing with phenylhydrazine in either ethanol or glacial acetic acid. Aldol self-condensation of 1-aryl-4-cyanopyrrolidin-3-ones afforded dipyrrolo-[3,2-b:3′, 4′-d]pyran derivatives. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1841–1848, December, 2007.     

Formation of furo[3,2- c ]quinolone-2-carbonitriles and 4-oxo-4,5-dihydrofuro[3,2- c ]quinolone-2-carboxamides from reaction of quinoline-2,4-diones with 2-[bis(methylthio)methylene]malononitrile

Quinoline-2,4-diones reacted with 2-[bis(methylthio)methylene]malononitrile in DMF/Et3N to produce 3-(methylthio)-4-oxo-4,5-dihydrofuro[3,2-c]quinolone-2-carbonitriles and 3-(methylthio)-4-oxo-4,5-dihydrofuro[3,2-c]quinolone-2-carboxamides in state of 2-imino-substituted 4-(methylthio)-5,6-dihydro-2H-pyrano[3,2-c]quinolone-3-carbonitriles. The structures of all new products were proved using NMR, IR, and mass spectral data. The possible mechanism for the reaction is also discussed.