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.     

A new method for the synthesis of [1,4]diazepino[6,5-b]indole derivatives

Reactions of 3-[(N-aryl-N-chloroacetyl)amino]-2-formylindoles with substituted anilines gave 1,4-diaryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indol-4-ium chlorides and those with 4-aminopyridine yielded 4-amino-1-(1-aryl-2-oxo-2,5-dihydro-1H-pyrido[3,2-b]indol-3-yl)pyridinium chlorides. Reduction of 1,2,3,6-tetrahydrodiazepinoindol-4-ium chlorides afforded the corresponding hexahydro derivatives. An alternative synthesis of 1-(4-nitrophenyl)-3-oxo-4-phenyl-1,2,3,4,5,6-hexahydro[1,4]diazepino[6,5-b]indole from 3-[N-(4-nitrophenyl)amino]-2-[(phenylimino)methyl]indole was developed. The method involves the following sequence of transformations: reduction, chloroacetylation, and intramolecular alkylation. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2193–2199, December, 2006.     

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.     

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.     

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 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 chemical transformations of partially hydrogenated [1,2,4]triazolo[5,1-b]quinazolines

The reaction of 5-methyl-7-phenyl-4,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine with α,β-unsaturated carbonyl compounds in MeOH in the presence of MeONa affords partially hydrogenated aryl-substituted [1,2,4]triazolo[5,1-b]quinazolines. Hydrolysis, oxidation, reduction, and alkylation of 5,6,8-triphenyl-5,6,7,10-tetrahydro[1,2,4]triazolo[5,1-b]quinazoline were studied. The structure of one oxidation product, viz., 7-hydroxy-5,6,8-triphenyl-6,7-dihydro[1,2,4]triazolo[5,1-b]quinazoline, was established by X-ray diffraction. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 335—340, February, 2006.     

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 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 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.     

Acyl Indoles. III. The synthesis of [1,4] diazcpino [6,5-b ] indoles

The synthesis of 1,3,4,6-letrahydro-6-metliy]-2H,5H-[1,4]diazepino[6,5-b] indole-2,5-diones and 5-phenyl-3,6-dihydro[1,4]diazepino[6,5-b ]indole-2(lH)one is described. Also detailed is the, preparation of a 3-amino-2-benzoylindole.     

A novel synthetic route for the total synthesis of (±)-uleine

In this study, a new synthetic route for the total synthesis of (±)-uleine is described. The important step in the synthesis of this alkaloid consists of an intramolecular cyclization of the D ring of the azocino[4,3-b]indole skeleton. Reduction of (N-methyl){3-β-ethyl-4-oxo-2,3,4,9-tetrahydrospiro[1H-carbazole-1,2′(1,3)dithiolane]-2-yl}-2-acetamide with borane yielded the corresponding (N-methyl){3-β-ethyl-4-hydroxy-2,3,4,9-tetrahydrospiro[1H-carbazole-1,2′(1,3)dithiolane]-2-yl}-2-acetamide, which underwent acid-catalyzed ring closure to produce azocino[4,3-b]indole core. Finally, the synthesis of (±)-uleine was completed through several steps from the azocino[4,3-b]indole core.     

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.     

4a-Alkyl Derivatives of 5-Oxo-4H-4a,5-dihydroindeno[1,2-b]pyridine

High selectivity has been discovered for the C-alkylation of ambident anions of 5-oxo-1H-4,5-dihydroindeno[1,2-b]pyridines with ethyl bromoacetate, allyl, propargyl, and phenacyl bromides, which leads to the formation of the corresponding 4a-substituted 5-oxo-4H-4a,5-dihydroindeno[1,2-b]pyridines in high yield.     

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.     

About the synthesis of [1,2]diazepinoindole derivatives from ethyl 2-(1-methylindole)acetate, 2-indole and 3-indoleacetohydrazones

The Vilsmeier-Haack reaction with ethyl 2-(1-methylindole)acetate and N,N-Dimethylamides/phosphorus oxychloride gave (65–85%) of ethyl 2-(3-acyl-1-methylindole)acetates 2 , which when boiled with hydrazine yielded about 90% of 4,5-dihydro-6-methyl-4-oxo-3H[1,2]diazepino[5,6-b]indoles 3. The attempted cyclization of 2-(1-methylindole)acetohydrazones 6 with acyl (acetyl and benzoyl) chlorides/triethylamine, to [1,2]diazepino[5,6-b]indole derivatives was fruitless and the bis(acyl)hydrazones 9 were obtained. Several transformations of 9 are reported. Similarly, the attempted cyclization of 3-indoleacetohydrazones 14 with acetyl chloride/triethylamine to [1,2]diazepino[4,5-b]indole derivatives was also fruitless and the bis(acyl)hydrazones 16 were again obtained.     

Condensed Isoquinolines. 17. Enamine Properties of Benzimidazo[1,2-b]isoquinolin-11(5H)-one in Alkylation Reactions

The alkylation of benzimidazo[1,2-b]isoquinolin-11(5H)-one has been studied. This occurs at N₍₅₎ or C₍₆₎ depending on the type of alkylating agent and the reaction conditions. It was shown that C₍₆₎ alkylation is effected in reactions with reactive alkyl halides. A repeat alkylation occurs preferentially at the same position. Interaction with o-xylylidene dibromide leads to spiro[benzimidazo[1,2-b]-isoquinolin-6,2'-indan]-11-one and 1,6-dihydro-11H-6a,11b-diazobenzo[b]benzo[5,6]cyclohepta[1,2,3-l,m]fluoren-11-one, which are derivatives of new heterocyclic systems.     

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.     

Spatial Configuration of Derivatives of 5,5a,6,7-Tetrahydropyrido[1,2-a]benzimidazole and 6,7-Dihydro-5aH-pyrido[1,2-b]benzoxazole

The spatial configurations of 7,9-diphenyl-5a,6-tetramethylene-5,5a,6,7-tetrahydropyrido[1,2-a]benzimidazole and 7,9-diphenyl-5a,6-tetramethylene-2,5a,6,7-tetrahydropyrido[1,2-a]benzimidazol-2-one have been established by X-ray crystallography. Analogous configurations are proposed for a series of other derivatives of 5,5a,6,7-tetrahydropyrido[1,2-a]benzimidazoles and some derivatives of 6,7-dihydro-5aH-pyrido[1,2-b]benzoxazoles on the basis of ¹H NMR spectroscopic data and the results of quantum chemical calculations using the MNDO, AM1, and PM3 methods.     

2-Chloro-3-quinolinecarboxaldehyde in the Synthesis of Condensed Quinoline Systems. 1. Synthesis of Derivatives of 3,4-Dihydro-2H-[1,3]thiazino[6,5-b]quinolines

A method for the synthesis of derivatives of previously unknown heterocyclic systems - 3,4-dihydro-2H-[1,3]thiazino[6,5-b]quinolines - has been developed based on 7,8-dimethyl-2-chloro-3-quinolinecarboxaldehyde via the consecutive steps of conversion into its Schiff's base with a primary amine, reduction to the corresponding aminomethyl derivative, conversion to the thiourea with isothiocyanates, and heterocyclization by intramolecular substitution of the chlorine atom.