Synthesis and properties of [1,4]diazepino[6,5-b]indoles

1-Aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxides were synthesized based on 3-(N"-aryl-N"-chloroacetyl)amino-2-formylindoles. Deoxidation of 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole N-oxide afforded 1,2,3,6-tetrahydro- and 1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole derivatives. A new approach to the synthesis of pyrido[3,2-b]indole and pyrimido[5,4-b]indole derivatives was developed.     

On the reduction of 1-aryl-2-oxo-1,2,3,6-tetra-hydro[1,4]diazepino[6,5-<Emphasis Type="Italic">b</Emphasis>]indole 4-oxides

Electrochemical reduction of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides, 2-oxo-1-phenyl-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole, and 2-oxo-1-phenyl-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole was studied. The results obtained were compared with previous data for the reduction of 4-oxides with formamidinesulfinic acid.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2715–2718, December, 2004.     

Synthesis and study of some properties of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides

A number of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides were synthesized based on 3-[N-aryl-N-(chloroacetyl)amino]-2-formylindoles. The nature of the substituent in the 1-aryl fragment has a pronounced influence on the course of reactions throughout the whole sequence of transformations during the synthesis of diazepinoindoles. The reduction of 4-oxides by formamidinosulfinic acid, hydrogen in the presence of Pd/C, and sodium bisulfite was studied. The structures of the reaction products were confirmed using IR and ¹H NMR spectroscopy and mass spectrometry.     

Reactions of 3-[N-chloroacetylamino-N-(4-nitrophenyl)]-2-formylindole with alkylamines

The reactions of 3-[N-chloracetylamino-N-(4-nitrophenyl)]-2-formylindole (1a) with 2-(N, N-dialkylamino)ethylamines afford complex condensation products 7b,c consisting of two similar but not identical diazepinoindole fragments. For the reaction of compound 1a with 3-(N,N-diethylamino)propylamine, the process occurs in a different manner, and the predominant product is 4-ethylaminopropyl-1-(4-nitrophenyl)-2-oxo-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole hydrocloride (14). Two routes of these unexpected transformations were proposed. The structures of the synthesized products were proved by the ¹sH and ¹³C NMR, HMBC, and HSQC (direct proton-carbon correlation) spectra. Dedicated to Academician V. A. Tartakovsky on the occasion of his 75th birthday. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1536–1542, August, 2007.     

Synthesis of 3-alkyl-1,4-dihydrocyclopenta[b]indoles: unexpected formation of dimeric compounds

Acid-catalyzed dehydration of 3-alkyl(aryl)-4-methyl-1,2,3,4-tetrahydrocyclopenta[b]indol-3-ols gives dimeric derivatives of 3-alkyl(aryl)-4-methyl-1,4-dihydrocyclopenta[b]indole.     

Synthesis of derivatives of a new heterocyclic system,indolo[2,3-f][1,7]naphthyridine

3-(N"-Aryl-N"-chloroacetyl)amino-2-formylindoles were converted into 3-amino-1-aryl-2-oxo-1,2-dihydropyrido[3,2-b]indoles, which were used to synthesize derivatives of a new heterocyclic system, namely, indolo[2,3-f][1,7]naphthyridine. The structures of the resulting compounds were proved by IR and ¹H NMR spectroscopy and mass spectrometry.     

Synthesis of derivatives of a new heterocyclic system pyrazolo[3,4-b]pyrido[1′,2′: 1,2]imidazo[4,5-d]pyridine

1-[4-Aminoarylpyrazolo[3,4-b]pyridin-5-yl]pyridinium chlorides undergo cyclization under reflux in tert-butanol in the presence of an excess of potassium tert-butoxide to form tetracyclic derivatives of pyrazolo[3,4-b]pyrido[1′,2′:1,2]imidazo[4,5-d]pyridine. The reaction scheme of the processes is proposed. The structures of the reaction products were confirmed by physicochemical methods. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 710–714, April, 2006.     

One-step synthesis of 5-acetyl-2-amino-4-aryl-3-cyano-4H-pyrano[3,2-b]indoles. Molecular and crystal structure of 5-acetyl-2-amino-4-(4"-chloro-3"-nitrophenyl)-3-cyano-4H-pyrano[3,2-b]indole

A one-step procedure was developed for the synthesis of 5-acetyl-2-amino-4-aryl-3-cyano-4H-pyrano[3,2-b]indoles involving the three-component reaction of 1-acetylindol-3(2H)-one with aromatic aldehydes and malononitrile in ethanol in the presence of triethylamine as the catalyst. The structure of 5-acetyl-2-amino-4-(4"-chloro-3"-nitrophenyl)-3-cyano-4H-pyrano[3,2-b]indole was established by X-ray diffraction analysis.     

A new methodology of annelation of five- and seven-membered heterocycles to quinoxalines

Pyrazolo[3,4-b]-, isoxazolo[4,5-b]-, benzo[2,3]-1,4-diazepino-, and benzo[2,3]-1,4-oxazepinoquinoxalines were prepared by reactions of 2-quinoxalinecarboxaldehyde with 1,2-N,N-, 1,2-N,O and 1,4-N,N- and 1,4-N,O-dinucleophiles.     

Synthesis of functional 2-substituted 4-phenyl-9H-pyrimido[4,5-b]indoles

A method was developed for the synthesis of 2-oxo-4-phenyl-2,3-dihydro-9H-pyrimido[4,5-b]indole as well as of 2-chloro- and 2-nitramino-4-phenylpyrimido[4,5-b]indoles. The replacement of the chlorine atom in 2-chloropyrimidoindole gave rise to a number of its functional derivatives (morpholino, azido, and cyano). The reaction of 2-chloro-substituted pyrimidoindole with hydrazine hydrate and catalytic hydrogenation of 2-nitraminopyrimidoindole were studied.     

Synthesis and Properties of Derivatives of the new Heterocyclic System Benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine

Derivatives of a new heterocyclic system - benz[4,5]imidazo[1,2-c]pyrido[3',2';4,5]thieno[2,3-e]pyrimidine have been obtained by successive reactions in three stages - alkylation of 3-cyanopyridine-2(1H)-thiones with 2-chloromethylbenzylimidazole to give 2-benzimidazolylmethylthio-3-cyanopyridines, closing the thiophene ring in the latter to form 3-amino-2-(benzimidazolyl-2)thieno[2,3-b]pyridines, and cyclization of the pyrimidine ring by acylation with carboxylic acid anhydrides or chlorides.     

A reinvestigation of the synthesis of 3H-[1,2]diazepino[5,6-b]indoles. The synthesis of pyrido[4,3-b]indoles

Recently reported [1] syntheses of 6-methyl-1,2,4,5-tetrahydro-1,4-dioxo-3H[1,2]diazepino[5,6-b]indole ( 5 ) and 4-hydroxy-6-methyl-3H[1,2]diazepino[5,6-b]indole ( 12 ) were reinvestigated and shown to be in error. The correct assignments for these respective structures are 3-amino-1,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2,4(3H)-dione ( 6 ) and 3-amino-3,9-dihydro-9-methyl-2H-pyrido[4,3-b]indol-2-one ( 13 ). Condensation of 6 and 13 with p-nitrobenzaldehyde produced benzylidene derivatives, which confirmed the presence of the amino groups.     

Synthesis and Reactions of 4-Oxiranylmethylfuro[3,2-b]pyrroles and Their Benzo Derivatives

Methyl 4-oxiranylmethyl-4H-furo[3,2-b]pyrrole-5-carboxylates 2a-c and methyl 1-oxiranylmethyl-1H-benzo[4,5]furo[3,2-b]pyrrole-2-carboxylate (2d) were prepared by reaction of the appropriate starting compounds 1a-d with excess chloromethyloxirane. The compounds 2a-d undergo oxirane ring opening by heterocyclic amines (morpholine, pyrrolidine, piperidine or 4-methylpiperazine) giving N-2-hydroxy-3-heteroaminopropyl-substituted compounds 3a-f or substituted 4,5-dihydrofuro[2',3':4,5]pyrrolo[2,1-c][1,4]oxazin-8-ones 4a-e.     

Synthesis of 8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine

8-tert-Butyl-9-oxo-1,2,4-triazolo[4,5-b]-1,2,4-triazolo[3,4-c]-1,2,4-triazine has been synthesized by the interaction of 6-tert-butyl-3-hydrazino-1,2,4-triazolo[3,4-c]-1,2,4-triazin-5-one with formic acid. The conditions of carrying out the reaction are discussed. Spectral characteristics are given.     

Synthesis of hexahydroazonino[5,6-b]indoles from hexahydroazepino[4,3-b]-and-[3,4-b]indoles and activated alkynes

A reaction of substituted hexahydroazepino[4,3-b]-and-[3,4-b]indoles with activated alkynes was studied. A one-step method for the synthesis of isomeric hexahydroazonino[5,6-b]indoles different by positions of the double bond in the azonine ring was developed. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2244–2250, November, 2007.     

Unusual scission of 3,7-dichlorobisisothiazolo[4,5-b:4",5"-e]pyrazine by nucleophiles

The reaction of 3,7-dichlorobisisothiazolo[4,5-b:4",5"-e]pyrazine with MeONa in MeOH afforded 3-chloro-5,6-dimethoxyisothiazolo[4,5-b]pyrazine. The reactions of the former with benzylamine, morpholine, and aniline gave rise to the corresponding N,N"-bis(5-amino-3-chloroisothiazol-4-yl)diazenes. In the case of benzylamine, 3,7-bis(benzylamino)bisisothiazolo[4,5-b:4",5"-e]pyrazine was isolated as a by-product. The crystal structure of N,N"-bis(5-benzylamino-3-chloroisothiazol-4-yl)diazene was established by X-ray diffraction analysis.     

4-Oxo-3,4-dihydroquinazolinyl- and Benzimidazolylacetonitriles in Annelation Reactions of a Haloquinoline Ring

The interaction of 4-oxo-3,4-dihydroquinazolinyl- and benzimidazolylacetonitriles with 2,6-dihalobenzaldehydes leads to 3-(2,6-dihalophenyl)-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles and 2-(1H-benzo[d]imidazol-2-yl)-3-(2,6-dihalophenyl)acrylonitriles respectively. As a result of intramolecular cyclization of these nitriles 4-halo-12-oxo-12H-quino[2,1-b]quinazoline-6-carbonitriles and 4-halobenzo[4,5]imidazo[1,2-a]quinoline-6-carbonitriles respectively are formed.     

Synthesis of 2-aryl-6,6-dimethyl-8-oxo-5,6,7,8-tetrahydro-1,2,4-4H-triazolo[3,2-b]benzothiazoles and their 3-aryl-[3,4-b] isomers

Summary Condensation of 3-aryl-5-thio-1,2,4-4H-trizoles (2a–i) and 2-bromodimedone (3) inTHF/benzene gave 2-aryl-6,6-dimethyl-8-oxo-5a-hydroxy-5,5a,6,7,8,8a-hexahydro-1,2,4-4H-triazolo[3,2-b]benzothiazoles (5a–i). These were also obtained by a one step synthesis on heating a mixture of dimedone,NBS, and2a–i in benzene containing a trace of benzoyl peroxide. Thermal dehydration of5a–i inPPA/anhydrous ethanol yielded the corresponding 2-aryl-6,6-dimethyl-8-oxo-5,6,7,8-tetrahydro-1,2,4-4H-triazolo[3,2,b]benzothiazoles (6a–i). The formation of [3,4-b] fused isomers (4a–i) during the reaction of2 with3 was ruled out by an unambiguous synthesis of8a–i. Antibacterial screening of selected compounds againstEscherichia coli andStaphylococcus aureus was not encouraging.

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Synthese von 2-Aryl-6,6-dimethyl-8-oxo-5,6,7,8-tetrahydro-1,2,4-4H-triazolo[3,2-b]benzothiazolen und ihrer 3-Aryl-[3,4-b]-Isomeren

Zusammenfassung Die Kondensation von 3-Aryl-5-thio-1,2,4-4H-triazolen (2a–i) mit 2-Bromdimedon (3) inTHF/Benzol ergab 2-Aryl-6,6-dimethyl-8-oxo-5a-hydroxy-5,5a,6,7,8,8a-hexahydro-1,2,4,-4H-triazolo[3,2-b]benzothiazole (5a–i). Dasselbe Ergebnis wurde durch Erhitzen einer Mischung von Dimedon,NBS und2a–i in Benzol unter Zusatz einer Spur Benzoylperoxid in einer einstufigen Synthese erreicht. Thermische Dehydrierung von5a–i inPPA/Ethanol(abs.) ergab die entsprechenden 2-Aryl-6,6-dimethyl-8-oxo-5,6,7,8-tetrahydro-1,2,4-4H-triazolo[3,2-b]benzothiazole (6a–i). Die Bildung [3,4-b]-kondensierter Isomere (4a–i) während der Reaktion von2 mit3 konnte durch eine eindeutige Synthese von8a–i ausgeschlossen werden. Antibakterielles Screening ausgewählter Verbindungen gegenüberEscherichia coli undStaphylococcus aureus brachte keine ermutigenden Resultate.

     

Synthesis and Properties of Substituted Isoxazolo[3',4':4,5]thieno[2,3-b]pyridines

We synthesized derivatives of a novel heterocyclic system, isoxazolo[3',4':4,5]thieno[2,3-b]pyridine by sequential conversions in three steps: isomerization of 2-(2-R-ethylthio-2-oxo)-3-pyridyl cyanides obtained by alkylation from substituted 3-cyano-2(1H)-pyridinethiones by -halomethyl ketones in alkaline medium, to form 3-aminothieno[2,3-b]pyridines; diazotization of the amino group followed by nucleophilic substitution of the diazonium group by an azido group, bypassing the step of isolating the diazonium salts; and thermolysis of the azides formed.     

Synthesis of 3-substituted cyclopenta[b]indoles

When reacting with I₂, 2-(cyclopent-2-enyl)anilines undergo cyclization into 3-iodo-1,2,3,3a,4,8b-hexahydrocyclopenta[b]indoles in high yields. The minor reaction products were 3,5- or 3,7-diiodoindolines. Ammonolysis of 3-iodo-5-methyl-1,2,3,3a,4,8b-hexahydro-cyclopenta[b]indole or itsN-chloroacetyl derivative results in 3-amino-5-methyl-1,2,3,3a,48b-hexahydro- and 5-methyl-1,3a,4,8b-tetrahydrocyclopenta[b]indoles. Published inIzvestiya Akademii Nauk. Seriya Khimischeskaya, No. 10, pp. 1789–1793, October, 2000.