Total assignment of the 1H NMR spectra of 5H-indolo[1,7-ab] [1]benzazepine,6,7-dihydro-5H-indolo[1,7-ab][1]benzazepine and pyrrolo[3,2,1-kl ] phenothiazine

The total assignment of the ¹H nmr spectrum of the three tetracyclic compounds: 5H -indolo[1,7-ab][1]benzazepine,6,7-dihydro-5H -indolo[1,7-ab ][1]benzazepine and pyrrolo[3,2,1-kl ]phenothiazine is described. Assignments were based on decoupling experiments and the spectrum of 1,10-dideuteriopyrrolo[3,2,1-kl]phenothiazine and the spectral parameters were verified by spin-simulation techniques. A temperature study of 6,7-dihydro-5H -indolo[1,7-ab][1]benzazepine was also performed.     

Indolo[1,7-ab][1]benzazepine,a new 18 π-electron heterocycle

The synthesis of indolo[1,7-ab][1]benzazepine was accomplished by cyclization of 5H-dibenz[b,f]azepine-5-acetaldehyde.     

Mass Spectral fragmentation patterns of heterocycles. V . Electron impact promoted mass spectral fragmentation of indolo[1,7-ab][1]benzazepine and Some of its Derivatives

The fragmentation patterns of 1,2,6,7-tetrahydroindolo[1,7-ab][l]benzazepin-1-one ( 1 ), 6,7-dihydroindolo-[1,7-ab][l]benzazepine ( 2 ) and indolo[1,7-ab][1]benzazepine ( 3 ) on electron impact have been examined. Loss of carbon monoxide to form the base peak at m/e 207 and loss of CHO radical to give m/e 206 consititute the major fragmentation pathways for 1. The moleclar ions ( M ⁺) are abundant for each of the compounds; observed as the second most intense peak for 1 (85% relative intensity) and the base peaks for 2 and 3 . The spectrum of 2 is characterized by intense M-1 and M-2 ions and by the presence of a M-15 ion (m/e 204) of moderate intensity (11.4%). In all other respects the spectra of 2 and 3 are strikingly similar. The M-15 ion from 2 , assigned the heteroaromatic pyrroloacridinium structure, is also formed in the spectrum of 1. A second heteroaromatic ion at m/e 191, common to the spectra of 1 , 2 and 3 , is believed to have the pyrrolocarbazol-ium structure. Metastable ion transitions and exact mass measurements support most of the proposed fragmentation pathways and structural assignments.     

Research on nitrogen heterocyclic compounds. XII. Synthesis of 5H-pyrrolo[1,2-b][2]benzazepine derivatives

Several routes to the synthesis of the unknown 5H-pyrrolo[1,2-b][2]benzazepine ring system have been explored. 1-(2-Cyanobenzyl)pyrrole was useful as starting material to obtain 1-(2-earboxymelhylbenzyl)pyrrole and 1-(2-chloromethylbenzyl)-2-pyrrolecarboxaldehyde. Poly-phosphoric acid catalyzed intramolecular cyclization of the former substance and treatment of the latter compound with potassium cyanide led to 11-oxo-10,11-dihydro-5H-pyrrolo[1,2-b]-[2]benzazepine and to 10-cyano-5H-pyrrolo[1,2-b][2]benzazepine, respectively. Starting from these materials the synthesis of the parent nucleus 5H-pyrrole[1,2-b][2]benzazepine and its 10,11-dihydro- and 1,2,3,10,11,11a-hexahydroderivatives has been realized.     

Synthesis of 1,2-dihydroindolo [1,7-AB] [1,5] benzodiazepines and related structures. A new heterocyclic ring system

The synthesis of the novel 1,2-dihydroindolo [1,7-ab][1,5]benzodiazepine ring system 4 is described. Condensation of 2-fluoronitrobenzene with indoline provided the starting material for the synthesis, 1-(2-nitrophenyl)indoline (1a) in high yield. The nitro group was reduced catalytically and the resulting amino function was acylated to afford the heterocycle percursor amide 3. Refluxing this amide in phosphorus oxychloride brought about a Bischler-Napieralski type cyclodehydration to form the target 1,2-dihydroindolo[1,7-ab][1,5]benzodiazepine ring system. Dehydrogenation of the latter led to the fully aromatic indolo[1,7-ab][1,5]benzodiazepine structure 5, while reduction with sodium borohydride provided the 1,2,6,7-tetrahydroindolo[1,7-ab]-[1,5]benzodiazepine tetracycle 6.     

Polycyclic N-heterocyclic compounds. XLI. Synthesis of 4-substituted 6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepines, 1,2,5,6-tetrahydro-4H-imidazo[1′,2′:1,6]pyrimido[5,4-d][1]benzazepines and their related compounds as a series of potential blood platelet aggregation inhibitors

As a series of polyheterocyclic compounds for exploitation as anti-platelet agents, tricyclic heterocyclic compounds, 4-substituted 6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepines 3–6, 9, 12–14 , and 16–26 , having nitrogen, oxygen, or sulfur containing functional groups at the 4-position, were prepared. In addition, tetra-cyclic heterocyclic compounds, 3-methyl-1,2,5,6-tetrahydro-4H-imidazo[1′,2′:1,6]pyrimido[5,4-d][1]benzaze-pinium chloride ( 7 ), 1,2,5,6-tetrahydro-4H-imidazo[1′,2′:1,6]pyrimido[5,4-d][1]benzazepines 10a-e , 2,3,6,7-tetrahydro-1H 5H-pyrimido[1′,2′:1,6]pyrimido[5,4-d][1]benzazepine ( 11 ), and 1,2,5,6-tetrahydro-4H-thiazolo-[3′,2′:1,6]pyrimido[5,4-d][1]benzazepinium chloride ( 15 ) via ring closure of 4-(hydroxyalkylamino)- 6, 9a-e , and 3c , and 4-(2-hydroxyethylthio)-6,7-dihydro-5H-pyrimido[5,4-d][1]benzazepine ( 14 ) with phosphoryl chloride or thionyl chloride, respectively, were also prepared. Their inhibitory activities against collagen-induced aggregation of rabbit blood platelets in vitro were investigated. Among them, compound 5 having a morpholino group at the 4-position on the tricyclic nucleus, which enhanced the activity more than 14-fold as compared with aspirin, was found to have the most satisfactory in inhibitory activity.     

Synthesis of [1]benzothienonaphthyridines

3-Chlorobenzo[b]thiophene-2-carbonyl chloride reacted readily with 2-amino-, 3-amino-, or 4-aminopyridine to give the corresponding amides. Photocyclization of the amides afforded the following lactams: [1]ben-zothieno[2,3-c][1,5]naphthyridin-6(5H)-one ( 14 ), [1]benzothieno[2,3-c][1,6]naphthyridin-6(5H)-one ( 7 ), [1]benzo-thieno[2,3-c][1,7]naphthyridin-6(5H)-one ( 11 ), and [1]benzothieno[2,3-c][1,8]naphthyridin-6(5H)-one ( 3 ). These lactams have been converted to other derivatives including in two instances the unsubstituted ring system.     

Galanthamine analogs: 6H-benzofuro[3a,3,2,-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3]benzazepine

The known cholinesterase inhibitory capability of the Amarylidaceae alkaloid galanthamine prompted preparation of analogs in which the position of the nitrogen within the azepine ring is altered. The analogs 6H-benzofuro[3a,3,2-e,f][1]benzazepine and 6H-benzofuro[3a,3,2-e,f][3]benzazepine were prepared in 19 and 2.5%, respectively, following Kametani and Shimizu approaches, respectively. The aniline derivative 6H-benzofuro[3a,3,2-e,f][1]benzazepine failed to undergo most of the reactions typical for galanthamine. Thus, it neither oxidized to the analogous narwedine, nor epimerized to the analogous epigalanthamine, nor reduced to the lycoramine analog, under the conditions used for galanthamine.     

A facile one-pot regioselective synthesis of functionalized novel benzo[f]chromeno[4,3-b][1,7]naphthyridines and benzo[f][1,7]naphthyridines via an imino Diels-Alder reaction

A novel series of functionalized 13H-benzo[f]chromeno[4,3-b][1,7]naphthyridines and 1,3-diphenylbenzo[f][1,7]naphthyridines have been synthesized by an efficient regioselective one-pot multicomponent synthesis through intra and intermolecular imino Diels-Alder reaction. In this method, we have achieved complete regioselectivity and atom economy with polysubstituted core motifs in moderate to good yields. The proposed mechanism of this reaction has also discussed.     

Facile synthesis and antifungal activity of 3-substituted 4-amino-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazines and pyrazolo[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepines

The reactions of the pyrazole-5-diazonium salt 3 with malononitrile and ethyl cyanoacetate gave 4-amino-3-cyano-8-ethoxycarbonylpyrazolo[5,1-c][1,2,4]triazine 7 and 4-amino-3,8-bisethoxycarbonylpyrazolo[5,1-c]-[1,2,4]triazine 8 , whose reactions with p-chloroaniline hydrochloride afforded 4-amino-8-ethoxycarbonyl-3-(p-chlorophenyl)amidinopyrazolo[5,1-c][1,2,4]triazine 9 and 4-amino-8-ethoxycarbonyl-3-(p-chlorophenyl)car-bamoylpyrazolo[5,1-c][1,2,4]triazine 10 , respectively. The reactions of 7 and 8 with o-phenylenediamine di-hydrochloride provided 9-ethoxycarbonyl-13H-spiro[benzimidazole-2′(3′H),6(5H)-pyrazolo[1,5′:3,4][1,2,4]tri-azino[5,6-b][1,5]benzodiazepine] hydrochloride 11a and 9-ethoxycarbonyl-6-oxo-13H-5,6-dihydropyrazolo-[1′,5′:3,4][1,2,4]triazino[5,6-b][1,5]benzodiazepine 12 , respectively. The antifungal activity of the above compounds was described.     

Tricyclic heteroaromatic systems. 5H-1,2,3-triazolo[5,1-c][1,4]benzodiazepine

The synthesis of the new tricyclic system 5H-1,2,3-triazolo[5,1-c][1,4]benzodiazepine, diaza-analogue of 5H-pyrrolo[2,1-c][1,4]benzodiazepine, which is the common feature of some antitumor antibiotics, is reported. The structure of the new tricyclic system and of some of its key intermediates is assigned by means of a ¹³C nmr study.     

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.     

A comparison of electron impact mass spectrometry of isomeric pyranocoumarins (pyrano[3,2-c][1]benzopyran-5-ones) and pyranochromones (pyrano[2,3-b][1]benzopyran-5-ones)

The mass spectrometric behaviour of two pairs of isomeric 2,2-dimethylpyrano[3,2-c][1]benzopyran-5-ones (pyranocoumarins) and 2,2-dimethylpyrano[2,3-b][1]benzopyran-5-ones (pyranochromones) and four pairs of isomeric 2-hydroxymethyl-2-methylpyrano[3,2-c][1]benzopyran-5-ones (pyranocoumarins) and 2-hydroxymethyl-2-methylpyrano[2,3-b][1] benzopyran-5-ones (pyranochromones) has been studied in detail with the aid of exact mass measurements, linked scans, collisionally activated decompositions and deuterium labelling experiments. The presence in both series of compounds of the same ions derived by structural interconversion of both molecular ions is emphasized, and structural information on the ions [C₇H₅O₂]⁺ (m/z 121), highly characteristic for these classes of compounds, as for 4-hydroxycoumarins, is reported.     

Synthesis of 5-amino-1,2,3,4-tetrahydrobenzo[b][1,7]naphthyridines and 2,3,4,4a,5,6-hexahydrobenzo[c][2,6]naphthyridines

This paper describes the synthesis of some 5-amino-1,2,3,4-tetrahydrobenzo[b][1,7]naphthyridines and 2,3,4,4a,5,6-hexahydrobenzo[c][2,6] naphthyridines starting from anilines and 1-benzyl-4-ethoxycarbonylpiperidin-3-one. The compounds were prepared in order to study their potential acetylcholinesterase inhibitory activity.     

Synthesis of 7-substituted 1H-indolo[3,2-d][1,2]benzoxazepines

The synthesis of the novel 7-substituted 1H-indolo[3,2-d][1,2]benzoxazepine ring system is described. Fischer indolization of 2-fluoroacetophenone phenylhydrazone provided the starting material 2-(2-fluorophenyl)-1H-indole. An acyl group was then introduced at the 3-position of the indole nucleus and the resulting ketone was converted to the ketoxime. Upon treatment with sodium hydride to form the oxanion of the ketoxime, an intramolecular cyclization took place via displacement of fluoride from the adjacent 2-fluorophenylsubstituent. This ring closure completed the construction of the 1H-indolo[3,2-d][1,2]benzoxazepine ring system.     

Synthesis of novel imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines

Several 1 1-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines have been used as starting material to prepare a number of derivatives of 9H-imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and 10H-pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines. The imidazole nucleus was built by reaction of amidines with ethyl bromopyruvate or aminoacetaldehyde dimethylacetal. Several derivatives of imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine have been prepared by formylation of the pyrrole ring followed by formation of thioamides. Condensation of 11-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines with diethyl ethoxymethylenemalonate afforded intermediate diesters which were transformed into the corresponding 10H-pyrimido[1,2-a]pyrrolo[2,1-c]-benzodiazepines.     

The Synthesis of Octahydro-7-phenylpyrazino[2,1-b][3]benzazepines

Octahydro-7-phenylpyrazino[2,1-b][3]benzazepine ( 1a ) was prepared from 1-methyl-3-phenylmethylpiperazine 5a by reaction with styrene oxide followed by sulfuric acid cyclization of the resulting alcohol 6a . The diastereomeric mixture 1a was further separated into the diastereomers 1a′ and 1a″ . Similarly 1-methyl-3-(3-chloro-4-methoxyphenyl)piperazine was reacted with styrene oxide to yield 6c which on cyclization with 1.5 equivalents of sulfuric acid in trifluoroacetic acid gave a 3:7 mixture of phenolic, 1d , and methoxy, 1c , octa-hydropyrazino[2,1-b][3]benzazepines. The reaction of the 2,5-piperazinedione 4c with sodium acetoxyborohydride gave a 49% yield of the 2-piperazinone 7 which was similarly carried on to the corresponding 1(2H)-oxohexahydropyrazino[2,1-b][3]benzazepine 9 .     

Synthesis of 6,7,8,9-tetrahydro-5H-pyrimido-[4,5-b][1,4]diazepine-6,8-diones

The sodium ethoxide catalyzed condensation of 4,5-diaminopyrimidine ( 3 ) with diethyl malonate afforded 6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione ( 4 ). Methylation of 6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione ( 4 ) using sodium hydride and two equivalents of iodomethane gave 5,9-dimethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione ( 5 ) which on further methylation using sodium hydride and one equivalent iodomethane yielded 6,7,8,9-tetrahydro-5,7,9-trimethyl-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione ( 6 ). Reaction of 6,7,8,9-tetrahydro-5H-pyrirnido[4,5-b][1,4]diazepine-6,8-dione ( 4 ) with 4.2 equivalents of sodium hydride and 4.1 equivalents of iodomethane afforded 6,7,8,9-tetrahydro-5,7,7, 9-tetramethyl-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione ( 7 ). 6,7,8,9-Tetrahydro-5,7,7,9-tetramethyl-5H-pyrimido[4,5-b][1,4]diazepine-6,8-dione ( 7 ) exhibited weak anticonvulsant activities in the subcutaneous pentylenetetrazole and maximal electroshock anticonvulsant screens indicating it is a partial bioisostere of the anticonvulsant drug clobazam ( 2 ).     

Synthesis and anticonvulsant activities of 5-(2-Chlorophenyl)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepines

A group of 5-(2-chlorophenyl)-10-(substituted)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepines 7a-c were synthesized by the acid catalyzed reaction of 5-(2-chlorophenyl)-2-hydrazino-3H-pyrido[3,4-e]-[1,4]diazepine ( 6 ) with either trimethyl orthoformate, triethyl orthoacetate or triethyl orthobenzoate, respectively. 5-(2-Chlorophenyl)-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepine ( 7a ) and 5-(2-chlo-rophenyl)-10-methyl-7H-pyrido[4,3-f][1,2,4]triazolo[4,3-a][1,4]diazepine ( 7b ) exhibited good anticonvulsant activity in the subcutaneous metrazol anticonvulsant screen which serves as a model for absence (petit mal) epilepsy.     

The synthesis of novel polycyclic heterocyclic ring systems.. Benzo[e][1]benzothieno[3,2-g][1]benzothiophenes

The novel polycyclic heterocyclic ring system compound, methyl 3-chlorobenzo[e][1]benzothieno-[3,2-g][1]benzothiophene-2-carboxylate was synthesized. The assignment of its ¹H and ¹³C nmr spectra was also accomplished by utilizing two-dimensional nmr methods.