- Direct formation of 4,5-disubstituted carbazolesviaregioselective dilithiation
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Carbazoles are widely exploited for their interesting photophysical and electronic properties, however bay (4,5-) functionalization is challenging, and previously inaccessible through carbazole C-H activation. We report a simple methodology which introduces a range of versatile 4,5-functionality, enabling the wider investigation of ring annulation and close proximity effects on carbazole properties.
- Pocock, Ian A.,Alotaibi, Alya M.,Jagdev, Kesar,Prior, Connor,Burgess, Gregory R.,Male, Louise,Grainger, Richard S.
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Read Online
- A 4 - hydroxy-carbazole new synthesis method (by machine translation)
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The invention belongs to the field of organic synthesis, in particular to a 4 - hydroxy-carbazole new synthesis method. The the new synthesis method to bromo nitrobenzene and neighbouring iodine anisole as raw material 3 step by the reaction of 4 - hydroxy-carbazole. The invention uses a 4 - hydroxy-carbazole new synthesis method, can significantly speed up the reaction rate and to improve the yield, not only reduces the cost, the protection of the environment, and the operation is simple, after treatment is convenient, and is suitable for industrial production. (by machine translation)
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- Synthesis of Glycoborine, Glybomine A and B, the Phytoalexin Carbalexin A and the β-Adrenoreceptor Antagonists Carazolol and Carvedilol
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We describe a regioselective synthesis of 4- or 5-substituted carbazoles by oxidative cyclisation of meta-oxygen-substituted N-phenylanilines. Using the regiodirecting effect of a pivaloyloxy group, we prepared 4-hydroxycarbazole, a precursor for the enantiospecific synthesis of the β-adrenoreceptor antagonists (?)-(S)-carazolol (5) and (?)-(S)-carvedilol (6). Regioselective palladium(II)-catalysed cyclisation of different diarylamines led to total synthesis of glycoborine (7) and the first total syntheses of the phytoalexin carbalexin A (8), glybomine A (9) and glybomine B (10). For glybomine B (10), a 5-hydroxycarbazole was converted into the corresponding triflate and utilized for introduction of a prenyl substituent.
- Brütting, Christian,Hesse, Ronny,J?ger, Anne,Kataeva, Olga,Schmidt, Arndt W.,Kn?lker, Hans-Joachim
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p. 16897 - 16911
(2016/11/17)
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- Recyclable copper catalyzed nitrogenation of biphenyl halides: A direct approach to carbazoles
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A novel A21-CuI catalyzed direct nitrogenation of biphenyl halides for the direct synthesis of carbazoles via a direct C-H amination process has been developed. A recyclable and inexpensive Cu-catalyst was successfully employed in N-heterocyclic compound synthesis via tandem azidation and C-H amination, which makes this protocol very practical and easy to handle.
- Ou, Yang,Jiao, Ning
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supporting information
p. 3473 - 3475
(2013/05/22)
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- COMPOUNDS AND METHODS FOR CARBAZOLE SYNTHESIS
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Compounds having bi-cyclic structure comprising a partially unsaturated 6-carbon first cyclic moiety interconnected to a 6-carbon second cyclic moiety second via a divalent linking moiety are provided. The compounds can be used as intermediates compounds in methods for the synthesis of carbazoles and derviatives thereof, including carvedilol, and tricyclic alkylhydroxamates, which do not require Fischer indole synthetic steps. Method of preparing the compounds having bi-cyclic structure are also provided.
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Page/Page column 30
(2008/06/13)
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- Method of producing 3,4,5,7,8,9-hexahydro-2h-dibenzofuran-1-one
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Disclosed is a process of producing 3,4,5,7,8,9-hexahydro-2H-dibenzofuran-1-one, and 1-hydroxydibenzofuran and 4-hydroxycarbazole using 3,4,5,7,8,9-hexahydro-2H-dibenzofuran-1-one as an intermediate. 2-chlorocyclohexanone and 1,3-cyclohexanedione are reacted with each other in a base and organic solvent to form a carbon-carbon bond, and then subject to a cyclization reaction in the presence of an acid solution to produce 3,4,5,7,8,9-hexahydro-2H-dibenzofuran-1-one. 3,4,5,7,8,9-hexahydro-2H-dibenzofuran-1-one as the intermediate is subjected to nitrogen substitution and dehydrogenation reactions to produce 4-hydroxycarbazole. 1-hydroxydibenzofuran is produced by dehydrogenating 3,4,5,7,8,9-hexahydro-2H-dibenzofuran-1-one. The process according to the present invention is advantageous in that a low-priced starting material is used to improve economic efficiency, the reaction is stable in specific base and organic solvent conditions, and 3,4,5,7,8,9-hexahydro-2H-dibenzofuran-1-one is produced at high yield because of the cyclization reaction in the presence of the acid solution. Furthermore, 1-hydroxydibenzofuran and 4-hydroxycarbazole can be stably and economically produced using the above intermediate.
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Page/Page column 8
(2008/06/13)
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- Concise and efficient synthesis of calothrixin B
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A convergent synthesis of the naturally occurring alkaloid Calothrixin B is presented, which used a regioselective hetero-Diels-Alder reaction between a "push-pull" 2-aza-diene and a N-protected 3-bromo-9H-carbazole-1,4- dione to construct the five-ring skeleton of the molecule. Protection of the indole motif with a benzyl group was unattractive for delivery of sufficient target material because the removal of the protecting group had not been high yielding. We therefore elected to temporarily protect the indole motif with a more labile benzyloxycarbonyl group. Accordingly, the synthesis of calothrixin B proceeded in 17% overall yield over 9 steps from the commercially available 1,2,3,9-tetrahydro-4H-carbazol-4-one.
- Sissouma, Drissa,Maingot, Lucie,Collet, Sylvain,Guingant, Andre
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p. 8384 - 8389
(2007/10/03)
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- PROCESS FOR THE PREPARATION OF CARVEDILOL
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A process for the preparation of carvedilol of formula (I) (I) either in enantiomeric substantially pure form, or as an enantiomeric mixture, optionally as a pharmaceutically acceptable salt thereof, which process comprises reacting 2,3-eopxypropoxy carbazole of formula (II) (II) or the R or S enantiomer thereof, with N-[2-(2-methoxy-phenoxy)ethyl]-benzylamine of formula (V) (V) to yield benzyl carvedilol of formula (VI) (VI) which is debenzylated by catalytic hydrogenation to yield carvedilol of formula (I), either in enantiomeric substantially pure form, or as an enantiomeric mixture, and if desired reacting the thus formed carvedilol of formula (I) with an inorganic or organic acid to yield a pharmaceutically acceptable salt thereof, and/or, if desired, separating the enantiomers. The above process is characterised in that reaction of said 2,3-epoxypropoxy carbazole of formula (II) with said N-[2-(2-methoxy-phenoxy)ethyl]-benzylamine of formula (V) is carried out in water as the reaction medium. The present invention further provides carvedilol of formula (I) prepared by a process as described above, and pharmaceutical compositions containing the same and therapeutic uses thereof.
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Page/Page column 14
(2008/06/13)
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- Synthesis of β3 adrenergic receptor agonist LY377604 and its metabolite 4-hydroxycarbazole, labeled with carbon-14 and deuterium
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Synthesis of 14C-radiolabeled 4-hydroxycarbazole was accomplished starting from aniline-[U-14C], based on zinc chloride initiated Fischer cyclization of the phenylhydrazone prepared from phenylhydrazine-[U-14C] and cyclohexane-1,3-dione. The resulting tetrahydrooxocarbazole was subjected to dehydrogenation-aromatization using palladium on carbon. The aromatized 4-hydroxycarbazole-[4b,5,6,7,8,8a- 14C] was then used for the synthesis of 14C-labeled β3 adrenergic receptor agonist LY377604. The introduction of four deuteria in the carbazole fragment of LY377604 accomplished by its initial bromination and subsequent catalytic deuteration of the resulting tetrabromide. A similar approach was used for the conversion of 4-hydroxycarbazole into its tetradeutero-isotopomer. Copyright
- Czeskis, Boris A.,Wheeler, William J.
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p. 407 - 419
(2007/10/03)
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- A synthesis of calothrixin B
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A new short and efficient synthesis of calothrixin B is reported. The key reaction is a hetero-Diels-Alder reaction between 3-bromo-9H-carbazole-1,4-dione and a 'push-pull' 2-aza-1,3-diene.
- Sissouma, Drissa,Collet, Sylvain C.,Guingant, André Y.
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p. 2612 - 2614
(2007/10/03)
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- Synthesis of Carbazole, Acridine, Phenazine, 4H-Benzo[def]carbazole and Their Derivatives by Thermal Cyclization Reaction of Aromatic Amines
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A variety of nitrogen-containing heterocycles were synthesized by passing vapors of aromatic amines over calcium oxide at 450-650 °C under nitrogen carrier gas. Reaction of 2-aminobiphenyl 3a at 560 °C gave carbazole 4 in 80% yield. Reaction of 2,2′-diaminobiphenyl 3b afforded a mixture of carbazole 4 and 4-aminocarbozole 6b. In the case of 2-amino-2′ -nitrobiphenyl 3c, benzo[c]cinnoline 7 was obtained along with carbazole 4. Reaction of 2-amino-2′-methoxybiphenyl 3d gave four products of carbazole 4, 4-hydroxycarbazole 6e, phenanthridine 8 and dibenzofuran 9. Reaction of 2-aminodiphenylmethane 5a afforded acridine 10. In the case of 2-aminobenzophenone 5b, acridone 11 was obtained as a major product. Reaction of 2-aminobenzhydrol 5c gave acridine 10. When 2-aminodiphenylamine 5d was reacted, phenazine 12 was obtained in good yield. In contrast, reaction of 2-aminodiphenyl ether 5e produced only 2-hydroxydiphenylamine 13. Reaction of 4-aminophenanthrene 14 produced 4H-benzo[def]carbazole 15 in 61% yield.
- Horaguchi, Takaaki,Oyanagi, Takako,Creencia, Evelyn Cuevas,Tanemura, Kiyoshi,Suzuki, Tsuneo
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- AMINOALKOXY CARBAZOLES FOR THE TREATMENT OF CNS DISEASES
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The present invention provides aminoalkoxy carbazole derivatives, and more specifically, provides compounds of formula (I) wherein R 1, R 2, R 3, R 4, R 8 and R 9 are described herein. These compounds are 5-HT ligands, and are useful for treating diseases wherein modulation of 5-HT activity is desired.
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- Process for preparing heterocyclic indene analogs
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A process for the preparation heterocyclic indene analogs, especially with the preparation of 4-hydroxycarbazole or N-protected 4-hydroxycarbazole, involves cyclocarbonylation followed by saponification. This process avoids high temperatures and high catalyst loadings.
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- Novel substituted 4-aminomethylpiperidines as potent and selective human β3-agonists. Part 1: Aryloxypropanolaminomethylpiperidines
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The synthesis and SAR of a series of human β3 adrenoreceptor agonists based on a template derived from a common pharmacophore coupled with 4-aminomethylpiperidine is described. Potent and selective agents were identified such as 26 that was in vitro active in CHO cells expressing human β3-AR (EC50=49 nM, IA=1.1), and in vivo active in a transgenic mouse model.
- Steffan, Robert J.,Ashwell, Mark A.,Solvibile, William R.,Matelan, Edward,Largis, Elwood,Han, Stella,Tillet, Jeffery,Mulvey, Ruth
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p. 2957 - 2961
(2007/10/03)
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- Oxygenation reactions of various tricyclic fused aromatic compounds using Escherichia coli and Streptomyces lividans transformants carrying several arene dioxygenase genes.
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Bioconversion (biotransformation) experiments on arenes (aromatic compounds), including various tricyclic fused aromatic compounds such as fluorene, dibenzofuran, dibenzothiophene, carbazole, acridene, and phenanthridine, were done using the cells of Escherichia coli transformants expressing several arene dioxygenase genes. E. coli carrying the phenanthrene dioxygenase (phdABCD) genes derived from the marine bacterium Nocardioides sp. strain KP7 converted all of these tricyclic aromatic compounds, while E. coli carrying the Pseudomonas putida F1 toluene dioxygenase (todC1C2BA) genes or the P. pseudoalcaligenes KF707 biphenyl dioxygenase (bphA1A2A3A4) genes was not able to convert these substrates. Surprisingly, E. coli carrying hybrid dioxygenase (todC1::bphA2A3A4) genes with a subunit substitution between the toluene and biphenyl dioxygenases was able to convert fluorene, dibenzofuran, and dibenzothiophene. The cells of a Streptomyces lividans transformant carrying the phenanthrene dioxygenase genes were also evaluated for bioconversion of various tricyclic fused aromatic compounds. The ability of this actinomycete in their conversion was similar to that of E. coli carrying the corresponding genes. Products converted from the aromatic compounds with these recombinant bacterial cells were purified by column chromatography on silica gel, and identified by their MS and 1H and 13C NMR analyses. Several products, e.g., 4-hydroxyfluorene converted from fluorene, and cis-1,2-dihydroxy-1,2-dihydrophenanthridine, cis-9,10-dihydroxy-9,10-dihydrophenanthridine, and 10-hydroxyphenanthridine, which were converted from phenanthridine, were novel compounds.
- Shindo,Ohnishi,Chun,Takahashi,Hayashi,Saito,Iguchi,Furukawa,Harayama,Horinouchi,Misawa
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p. 2472 - 2481
(2007/10/03)
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