- A Green Aerobic Oxidative Synthesis of Pyrrolo[1,2-a]quinoxalines from Simple Alcohols without Metals and Additives
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A practical and concise protocol for the efficient preparation of pyrrolo[1,2-a]quinoxalines through a cascade of alcohol oxidation/imine formation/intramolecular cyclization/oxidative dehydrogenation has been established. A series of substituted pyrrolo[1,2-a]quinoxaline derivatives were constructed readily in yields of 53-93% from the cheap primary alcohols by using dioxygen as the terminal oxidant. Remarkably, the fact that no extra metals and additives were necessary makes this unprecedented aerobic oxidation process highly step- and atom-economical. The usefulness of this transformation was further demonstrated with the gram-scale synthesis of compound 3aa under standard conditions.
- Li, Jixing,Zhang, Jinlong,Yang, Huameng,Gao, Zeng,Jiang, Gaoxi
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- Transition-metal-free N-arylation: A general approach to aza-fused poly-heteroaromatics
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A new and efficient method for the synthesis of various aza-fused poly-hetero aromatics has been described. This protocol includes an intermolecular condensation followed by metal-free base-promoted intramolecular C―N coupling reaction. The advantage of this one-pot transformation lies in the use of simple cyclic amidines-like compounds without prefunctionalization of the starting heterocycles.
- Annareddygari, Srikanth,Kasireddy, Venkateshwer Reddy,Reddy, Jayachandra
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- Efficient copper-catalyzed annulation of 2-formylazoles with 2-haloanilines for the synthesis of pyrrole- and imidazole-fused quinoxalines
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Promoted by CuI/2-hydroxybenzohydrazide catalytic system, a variety of pyrrole- and imidazole-fused quinoxalines have been efficiently one-pot synthesized from pyrrole-/imidazole-2-carboxaldehyde and 2-haloanilines in moderate to excellent yields. 2-Hydroxybenzohydrazide-promoted CuI-catalyzed one-pot annulation of pyrrole-/imidazole-2-carboxaldehyde with 2-haloanilines for the synthesis of pyrrolo[1,2-α]- and imidazo[1,2-α]quinoxalines under relatively mild conditions is described.
- Li, Zihao,Yan, Nannan,Xie, Jianwei,Liu, Ping,Zhang, Jie,Dai, Bin
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- Synthesis method of pyrrole[1,2-a]quinoxaline derivative
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The invention relates to a synthesis method of a pyrrole [1,2a] quinoxaline derivative. The method comprises the steps: dissolving a cuprous complex, 2-bromoaniline, a pyrrole formaldehyde compound and an alkali in an organic solvent, carrying out a reaction, and carrying out separation and purification to obtain the pyrrole[1,2a] quinoxaline derivative, wherein the molar ratio of the cuprous complex to the 2-bromoaniline to the pyrrole formaldehyde compound to the alkali is (0.01-0.03): 1.0: 1.0: 1.5, the reaction temperature is 50-65 DEG C, and the reaction time is 6-8 hours. Compared with the prior art, the method has the advantages of mild reaction conditions, high yield, high substrate universality, less waste and the like.
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Paragraph 0055-0058
(2021/03/11)
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- PEG-400 as a carbon synthon: Highly selective synthesis of quinolines and methylquinolines under metal-free conditions
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A metal-free, peroxide-free, and efficient procedure for the highly selective synthesis of quinolines and methylquinolines was reported. The main feature of this method was that the same substrate can produce quinolines and methylquinolines, respectively, under different reaction conditions. PEG-400 was used as both a reactant and solvent in this reaction. The utility of the designed procedure was also demonstrated by the derivatization of the products to bioactive compounds. This journal is
- Ding, Chengcheng,Feng, Kaili,Li, Shichen,Ma, Chen
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p. 5542 - 5548
(2021/08/16)
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- N,N-Dimethylformamide as Carbon Synthons for the Synthesis ofN-Heterocycles: Pyrrolo/Indolo[1,2-a]quinoxalines and Quinazolin-4-ones
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N,N-dimethylformamide (DMF) as synthetic precursors contributing especially the methyl, acyl, and amino groups has played a significant role in heterocycle syntheses and functionalization. In this protocol, a wide range of pyrrolo/indolo[1,2-a]quinoxalines and quinazolin-4-ones were obtained in moderate to good yields by using elemental iodine without any metal or peroxides. We considered thatN-methyl andN-acyl of DMF participate and complete the reaction separately through different mechanisms, which displayed potential still to be explored of DMF.
- Ding, Chengcheng,Li, Shichen,Ma, Chen,Ren, Jianing,Wang, Yishou
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p. 16848 - 16857
(2021/12/06)
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- α-Hydroxy acid as an aldehyde surrogate: metal-free synthesis of pyrrolo[1,2-a]quinoxalines, quinazolinones, and other N-heterocyclesviadecarboxylative oxidative annulation reaction
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A metal-free and efficient procedure for the synthesis of pyrrolo[1,2-a]quinoxalines, quinazolinones, and indolo[1,2-a]quinoxaline has been developed. The key features of our method include thein situgeneration of aldehyde from α-hydroxy acid in the presence of TBHP (tert-butyl hydrogen peroxide), and further condensation with various amines, followed by intramolecular cyclization and subsequent oxidation to afford the corresponding quinoxalines, quinazolinones derivatives in moderate to high yields.
- Jung, Chanhyun,Jung, Jae-Kyung,Lee, Heesoon,Lee, Kiho,Lee, Seohu,Park, Yunjeong,Sim, Jaeuk,Viji, Mayavan,Vishwanath, Manjunatha
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p. 37202 - 37208
(2020/10/28)
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- Pyrrolo[1,2-a]quinoxalines: Insulin Mimetics that Exhibit Potent and Selective Inhibition against Protein Tyrosine Phosphatase 1B
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PTP1B dephosphorylates insulin receptor and substrates to modulate glucose metabolism. This enzyme is a validated therapeutic target for type 2 diabetes, but no current drug candidates have completed clinical trials. Pyrrolo[1,2-a]quinoxalines substituted at positions C1–C4 and/or C7–C8 were found to be nontoxic to cells and good inhibitors in the low- to sub-micromolar range, with the 4-benzyl derivative being the most potent inhibitor (0.24 μm). Some analogues bearing chlorine atoms at C7 and/or C8 kept potency and showed good selectivity compared to TCPTP (selectivity index '40). The most potent inhibitors behaved as insulin mimetics by increasing glucose uptake. The 4-benzyl derivative inhibited insulin receptor substrate 1 and AKT phosphorylation. Molecular docking and molecular dynamics simulations supported a putative binding mode for these compounds to the allosteric α3/α6/α7 pocket, but inconsistent results in enzyme inhibition kinetics were obtained due to the high tendency of these inhibitors to form stable aggregates. Computational calculations supported the druggability of inhibitors.
- García-Marín, Javier,Griera, Mercedes,Sánchez-Alonso, Patricia,Di Geronimo, Bruno,Mendicuti, Francisco,Rodríguez-Puyol, Manuel,Alajarín, Ramón,de Pascual-Teresa, Beatriz,Vaquero, Juan J.,Rodríguez-Puyol, Diego
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p. 1788 - 1801
(2020/09/15)
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- Terminal methyl as a one-carbon synthon: Synthesis of quinoxaline derivatives: Via radical-type transformation
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An iron-promoted method for the construction of pyrrolo[1,2-a]quinoxaline derivatives has been developed. Ferric chloride served as a promoter and as a Lewis acid in the reaction. Solvents provided the corresponding carbon sources simultaneously. The majority of solvents with terminal methyl groups, including ethers, amines and dimethyl sulfoxide, were reactive in the synthesis of quinoxaline derivatives at a certain yield via C-H(sp3) amination/C-O or C-N (C-S) cleavage. This method was applicable to a wide range of pyrrolo[1,2-a]quinoxaline and indolo[1,2-a]quinazoline substrates.
- Wang, Xinfeng,Liu, Huanhuan,Xie, Caixia,Zhou, Feiyu,Ma, Chen
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p. 2465 - 2470
(2020/02/20)
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- N-arylation method in aqueous phase system with substituted quinoline or isoquinoyl hydrazide pyridine-N-oxide as ligand
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The invention relates to an N-arylation method in an aqueous phase system with substituted quinoline or isoquinoyl hydrazide pyridine-N-oxide as a ligand. The N-arylation method in the aqueous phase system with the substituted quinoline or isoquinoyl hydrazide pyridine-N-oxide as the ligand comprises the following steps of: adding a catalyst, the ligand, a raw material, alkali, a phase transferring catalyst and a solvent into a reactor, heating and stirring, after the reaction is ended, separating and purifying a reaction solution to obtain an N-arylation product, wherein the raw material is aryl halide and a nitrogen-containing nucleophilic reagent, the solvent is a mixed solution of water and ethanol, and the catalyst is metal copper, or a copper oxide, or monovalent copper salt, or bivalent copper salt. The N-arylation method in the aqueous phase system with substituted quinoline or isoquinoyl hydrazide pyridine-N-oxide as the ligand has the characteristics of simplicity in operation, wide substrate application range, simplicity and easiness in separating products, high yield, economical process, environmental protection and the like.
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Paragraph 0100; 0101; 0102; 0103
(2019/03/28)
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- Cu2O/1-(2-methylhydrazine-1-carbonyl)-isoquinoline 2-oxide catalyzed C-N cross-coupling reaction in aqueous media
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An experimentally simple, efficient, and inexpensive catalyst system was developed for the N-arylation of imidazole, indole, pyrrole, alkyl alcohol amines, and alkyl amines with aryl iodides and bromides. The reaction proceeds in water-ethanol media at 120 °C for 12 h with Cu2O as the catalyst, 1-(2-methylhydrazine-1-carbonyl)-isoquinoline 2-oxide (L2) as the ligand, NaOH as the base to generate a wide range of N-arylated products in moderate to excellent yields. Aqueous medium, ease of operation, and broad substrate scope give the process a benign environmental profile.
- Xie, Jian-Wei,Yao, Zhen-Bin,Wang, Xiao-Chuang,Zhang, Jie
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p. 3788 - 3792
(2019/06/08)
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- Unexpected activated carbon-catalyzed pyrrolo[1,2-a]quinoxalines synthesis in water
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An interesting and recyclable activated carbon/water catalytic system for efficient synthesis of pyrrolo[1,2-a]quinoxaline derivatives was developed. The intramolecular C–N and C–C bond can be easily constructed in water under mild condition. This reaction features a broad substrate scope, a good tolerance to water and air, metal-free, additive-free and redox reagent-free.
- Sun, Qi,Liu, Liyan,Yang, Yu,Zha, Zhenggen,Wang, Zhiyong
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p. 1379 - 1382
(2019/05/04)
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- Optimization of Drug Candidates That Inhibit the D-Loop Activity of RAD51
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RAD51 is the central protein in homologous recombination (HR) repair, where it first binds ssDNA and then catalyzes strand invasion via a D-loop intermediate. Additionally, RAD51 plays a role in faithful DNA replication by protecting stalled replication forks; this requires RAD51 to bind DNA but may not require the strand invasion activity of RAD51. We previously described a small-molecule inhibitor of RAD51 named RI(dl)-2 (RAD51 inhibitor of D-loop formation #2, hereafter called 2 h), which inhibits D-loop activity while sparing ssDNA binding. However, 2 h is limited in its ability to inhibit HR in vivo, preventing only about 50 % of total HR events in cells. We sought to improve upon this by performing a structure–activity relationship (SAR) campaign for more potent analogues of 2 h. Most compounds were prepared from 1-(2-aminophenyl)pyrroles by forming the quinoxaline moiety either by condensation with aldehydes, then dehydrogenation of the resulting 4,5-dihydro intermediates, or by condensation with N,N′-carbonyldiimidazole, chlorination, and installation of the 4-substituent through Suzuki–Miyaura coupling. Many analogues exhibited enhanced activity against human RAD51, but in several of these compounds the increased inhibition was due to the introduction of dsDNA intercalation activity. We developed a sensitive assay to measure dsDNA intercalation, and identified two analogues of 2 h that promote complete HR inhibition in cells while exerting minimal intercalation activity.
- Budke, Brian,Tueckmantel, Werner,Miles, Kelsey,Kozikowski, Alan P.,Connell, Philip P.
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p. 1031 - 1040
(2019/04/30)
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- Dimethyl Sulfoxide Involved One-Pot Synthesis of Quinoxaline Derivatives
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An efficient, green, and novel method for the synthesis of N-heterocycle-fused quinoxalines is reported herein. Dimethyl sulfoxide was used as both a reactant and a solvent in this reaction. A wide range of products in moderate to excellent yields were obtained, including pyrrolo[1,2-a]quinoxalines, indolo[1,2-a]quinoxalines, 1H-pyrrolo[3,2-c]quinolines, and benzo[4,5]imidazo[1,2-c]quinazolines.
- Xie, Caixia,Zhang, Zeyuan,Li, Danyang,Gong, Jian,Han, Xushuang,Liu, Xuan,Ma, Chen
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p. 3491 - 3499
(2017/04/11)
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- Synthesis of pyrrolo[1,2-: A] quinoxalines via copper or iron-catalyzed aerobic oxidative carboamination of sp3C-H bonds
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An aerobic oxidative carboamination of sp3C-H bonds with 2-(1H-pyrrol-1-yl)anilines has been developed. The oxidative carboamination processes utilized simple and readily available starting materials to produce pyrrolo[1,2-a]quinoxalines in good to moderate yields. The transformations also featured inexpensive metal catalysts (copper or iron) and a green oxidant (O2).
- Dai, Chenshu,Deng, Siqi,Zhu, Qiuhua,Tang, Xiaodong
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p. 44132 - 44135
(2017/09/26)
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- Iron-Catalyzed Intramolecular C(sp2)-N Cyclization of 1-(N-Arylpyrrol-2-yl)ethanone O-Acetyl Oximes toward Pyrrolo[1,2-a]quinoxaline Derivatives
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An efficient and convenient iron-catalyzed protocol has been developed for the synthesis of substituted pyrrolo[1,2-a]quinoxalines from 1-(N-arylpyrrol-2-yl)ethanone O-acetyl oximes through N-O bond cleavage and intramolecular directed C-H arylation reactions in acetic acid.
- Zhang, Zhiguo,Li, Junlong,Zhang, Guisheng,Ma, Nana,Liu, Qingfeng,Liu, Tongxin
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p. 6875 - 6884
(2015/10/06)
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- 4,5-Dihydropyrrolo[1,2-a]quinoxalines: A tunable and regenerable biomimetic hydrogen source
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A series of tunable and regenerable biomimetic hydrogen sources, 4,5-dihydropyrrolo[1,2-a]quinoxalines, have been synthesized and applied in biomimetic asymmetric hydrogenation of 3-aryl-2H-benzo[b][1,4]oxazines and 1-alkyl-3-aryl-quinoxalin-2(1H)-ones, providing the chiral amines with up to 92% and 89% ee, respectively.
- Chen, Zhang-Pei,Chen, Mu-Wang,Guo, Ran-Ning,Zhou, Yong-Gui
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supporting information
p. 1406 - 1409
(2014/04/03)
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- One-pot synthesis of pyrrolo[1,2-a]quinoxaline derivatives via iron-promoted aryl nitro reduction and aerobic oxidation of alcohols
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Here, we describe a new one-pot method to synthesize 4,7-substituted pyrrolo[1,2-a]quinoxalines and related heterocyles through a cascade of redox reactions/imine formation/intramolecular cyclization. This procedure tolerates readily available substituted 1-(2-nitrophenyl)pyrrole derivatives and aliphatic or benzylic alcohols as starting materials using iron powder and acidic conditions. This is the first example of constructing N-heterocycles via iron-mediated aryl nitro reduction and aerobic oxidation of alcohols in one pot.
- De Fatima Pereira, Maria,Thiery, Valerie
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supporting information
p. 4754 - 4757,4
(2012/12/12)
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- Copper-catalyzed annulation of 2-formylazoles with o-aminoiodoarenes
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(Chemical Equation Presented) In the presence of catalytic CuI and sparteine, 2-formylpyrroles can be annulated with o-aminoiodoarenes to give substituted pyrrolo[1,2-a]quinoxalines and related heterocycles. The reaction also works for annulation of 2-formylindoles, 2-formylimidazole, 2-formylbenzimidazole, and a 3-formylpyrazole.
- Reeves, Jonathan T.,Fandrick, Daniel R.,Tan, Zhulin,Song, Jinhua J.,Lee, Heewon,Yee, Nathan K.,Senanayake, Chris H.
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supporting information; experimental part
p. 992 - 994
(2010/05/19)
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- Expeditious synthesis of imidazole-and pyrrole-fused benzodiazocines
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A straightforward strategy for the synthesis of imidazolefused benzodiazocine from 1-(2-nitrophenyl)-1H-imidazole2-carbaldehyde via Morita-Baylls-Hillman reaction followed by reductive intramolecular cyclization is described. Alternatively the Horner-Wads
- Mishra, Amita,Batra, Sanjay
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scheme or table
p. 4832 - 4840
(2010/10/21)
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- Synthesis of pyrrolo[1,2-a]quinoxaline derivatives by lewis acid-catalyzed reactions of 1-(2-isocyanophenyl)pyrroles
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1-(2-Isocyanophenyl)pyrroles have been prepared. They react in moderate to good isolated yields with aldehydes (or ketones), oxiranes, and acetals in the presence of catalytic amounts of diethyl ether-boron trifluoride to give pyrrolo [1,2-a]quinoxalines carrying an oxyalkyl substituent, such as α-hydroxyalkyl, β-hydroxyalkyl, or α-alkoxyalkyl, at the 4-position.
- Kobayashi,Irisawa,Matoba,Matsumoto,Yoneda,Morikawa,Konishi
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p. 1109 - 1114
(2007/10/03)
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- Synthesis of pyrrolo[1,2-a]quinoxaline and its 4-(1-hydroxyalkyl) derivatives by Lewis acid-catalyzed reactions of 1-(2-isocyanophenyl)pyrrole
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When 1-(2-isocyanophenyl)pyrrole was treated with a catalytic amount of boron trifluoride, pyrrolo[1,2-a]quinoxaline was obtained almost quantitatively. The reaction in the presence of aldehydes or ketones gave the corresponding 4-(1-hydroxyalkyl)pyrrolo[1,2-a]quinoxalines in moderate to good isolated yields.
- Kobayashi, Kazuhiro,Matoba, Takeshi,Irisawa, Susumu,Matsumoto, Takashi,Morikawa, Osamu,Konishi, Hisatoshi
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p. 551 - 552
(2007/10/03)
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- Synthesis of the novel pyrrolo[2,1-d][1,2,5]benzotriazepine, pyrrolo[2,1-e][1,3,6]benzotriazocine and pyrrolo[1,2-a]tetrazolo[1,5-d][1,4]benzodiazepine ring systems. A new route to pyrrolo[1,2-a]quinoxaline via transamination of in situ generated 1-(2-aminophenyl)-2-iminomethylpyrroles
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Selective reduction of 2-azidomethyl-1-(2-nitrophenyl)pyrrole 5 afforded 2-aminomethyl-1-(2-nitrophenyl)pyrrole 10. Pyrrolo[1,2-a]quinoxaline 15 is obtained by treating aminoester 12 with formaldehyde. Diamine 8 reacts with either formaldehyde or benzaldehyde to give pyrrolo[1,2-a]quinoxaline 19. Compound 10 was reductively cyclised to pyrrolo[2,1-d][1,2,5]benzotriazepine 22. Intramolecular coupling of diamine 8 with triphosgene or carbon disulfide yields pyrrolo[2,1-e][1,3,6]benzotriazocine 23 and 24, respectively. Intramolecular 1,3-dipolar cycloaddition of cyanoazide 6 gives pyrrolo[1,2-a]tetrazolo[1,5-d][1,4]benzodiazepine 25.
- Korakas, Demetrios,Kimbaris, Athanasios,Varvounis, George
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p. 10751 - 10760
(2007/10/03)
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