- N, N, N', N'-Tetramethylethylenediamine-Enabled Photoredox-Catalyzed C-H Methylation of N-Heteroarenes
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Aiming at the valuable methylation process, readily available and inexpensive N,N,N′,N′-tetramethylethylenediamine (TMEDA) was first identified as a new methyl source in photoredox-catalyzed transformation in this work. By virtue of this simple methylating reagent, a facile and practical protocol for the direct C-H methylation of N-heteroarenes was developed, featuring mild reaction conditions, broad substrate scope, and scalability. Mechanistic studies disclosed that a sequential photoredox, base-assisted proton shift, fragmentation, and tautomerization process was essentially involved.
- Liu, Fang,Ye, Zhi-Peng,Hu, Yuan-Zhuo,Gao, Jie,Zheng, Lan,Chen, Kai,Xiang, Hao-Yue,Chen, Xiao-Qing,Yang, Hua
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- Electro-oxidative C-H alkylation of quinoxalin-2(1: H)-ones with organoboron compounds
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Radical cleavage of C-B bonds to accomplish C-H functionalization is synthetically appealing but practically challenging. We report herein a mild electro-oxidative method for efficient C-H alkylation of quinoxalin-2(1H)-ones by means of radical addition reactions of alkyl boronic acids and esters and alkyl trifluoroborates to afford C-C coupled products. This journal is
- Niu, Kaikai,Hao, Yanke,Song, Lingyun,Liu, Yuxiu,Wang, Qingmin
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supporting information
p. 302 - 306
(2021/01/28)
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- Electro-oxidative C-H azolation of quinoxalin-2(1H)-ones
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We have developed a practical, general protocol for direct C-H azolation reactions of quinoxalin-2(1H)-ones by electro-oxidative cross-coupling. These mild reactions proceed under metal-, oxidant-, and reagent-free conditions to provide synthetically useful azolated quinoxalin-2(1H)-ones. Furthermore, the reactions can be carried out with a pencil lead as an electrode and a 3 V battery as a power source, revealing the remarkable flexibility of this protocol.
- Ding, Ling,Hao, Yanke,Liu, Yuxiu,Niu, Kaikai,Song, Hongjian,Wang, Qingmin,Zhou, Pan
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supporting information
p. 3246 - 3249
(2021/05/21)
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- Electrochemical chlorination and bromination of electron-deficient C[sbnd]H bonds in quinones, coumarins, quinoxalines and 1,3-diketones
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The electrochemistry-promoted chlorination and bromination of electron-deficient C[sbnd]H bonds was developed, using quinones, coumarins, quinoxalines and 1,3-diketones. This protocol features readily available and safe halogen sources (hydrochloric acid and KBr), high site-selectivity and mild reaction conditions. It could provide an efficient access to a series of chlorinated and brominated quinones, coumarins, quinoxalines and 1,3-diketones.
- Yu, Dan,Ji, Ruixue,Sun, Zhihui,Li, Wenjie,Liu, Zhong-Quan
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supporting information
(2021/11/16)
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- K2S2O8-catalyzed highly regioselective amidoalkylation of diverse N-heteroaromatics in water under visible light irradiation
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A K2S2O8-catalyzed versatile C(sp2)-C(sp3) bond formation with N-heteroaromatics and γ-lactams/amides was developed. Quinoxalin-2(1H)-one, quinoline, isoquinoline, phthalazine, and benzothiazole reacted with γ-lactams/amides to give the corresponding C(sp2)-H amidoalkylation products in moderate to good yields with high regioselectivity. This visible-light-induced photocatalyst-free reaction was conducted in H2O at ambient temperature, which comply with the principles of "green chemistry". The new K2S2O8 catalytic mechanism was investigated with control experiments.
- Chen, Zhi,Li, Jianjun,Ren, Quanlei,Song, Shengjie,Wang, Chaodong,Xu, Ning,Zhou, Jiadi
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supporting information
p. 5753 - 5758
(2021/08/23)
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- Visible Light-Promoted Radical Relay Cyclization/C-C Bond Formation of N-Allylbromodifluoroacetamides with Quinoxalin-2(1 H)-ones
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A visible light-promoted radical relay of N-allylbromodifluoroacetamide with quinoxalin-2(1H)-ones was developed in which 5-exo-trig cyclization and C-C bond formation were involved. This protocol was performed under mild conditions to facilely offer a variety of hybrid molecules bearing both quinoxalin-2(1H)-one and 3,3-difluoro-γ-lactam motifs. These prepared novel skeletons would expand the accessible chemical space for structurally complex heterocycles with potential biological activities.
- Ye, Zhi-Peng,Liu, Fang,Duan, Xin-Yu,Gao, Jie,Guan, Jian-Ping,Xiao, Jun-An,Xiang, Hao-Yue,Chen, Kai,Yang, Hua
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p. 17173 - 17183
(2021/11/18)
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- Electrochemically C-H/S-H Oxidative Cross-Coupling between Quinoxalin-2(1 H)-ones and Thiols for the Synthesis of 3-Thioquinoxalinones
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An electrochemical method for the C(sp2)-H thioetherification of quinoxalin-2(1H)-ones with primary, secondary, and tertiary thiols has been reported. Various quinoxalin-2(1H)-ones underwent this thioetherification smoothly under metal- A nd chemical oxidant-free conditions, affording 3-alkylthiol-substituted quinoxalin-2(1H)-ones in moderate to good yields.
- Zhou, Jiadi,Li, Zhonghui,Sun, Zexu,Ren, Quanlei,Zhang, Qiwei,Li, Hu,Li, Jianjun
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p. 4365 - 4372
(2020/04/10)
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- Electrochemical decarboxylative C3 alkylation of quinoxalin-2(1: H)-ones with N -hydroxyphthalimide esters
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We have developed a protocol for electrochemical decarboxylative C3 alkylation of a wide range of quinoxalin-2(1H)-ones under metal- and additive-free conditions. N-Hydroxyphthalimide esters derived from chain, cyclic, primary, secondary, and tertiary carboxylic acids with a broad scope proved to be suitable substrates. This operationally simple protocol performed in an undivided cell under constant-current conditions is suitable for late-stage functionalization of quinoxalin-2(1H)-ones. The reactions can even be carried out with a 3 V battery as a power source, which demonstrates that organic electrosynthesis can be accomplished without the need for specialized equipment.
- Niu, Kaikai,Song, Lingyun,Hao, Yanke,Liu, Yuxiu,Wang, Qingmin
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supporting information
p. 11673 - 11676
(2020/10/20)
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- SUBSTITUTED 2-AZABICYCLO[3.1.1]HEPTANE AND 2-AZABICYCLO[3.2.1]OCTANE DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
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There is provided a compound of formula (I), wherein L1 to L3, R1 to R4, X, A and B have meanings given in the description, and pharmaceutically acceptable salts, solvates and prodrugs thereof, which compounds are useful as antagonists of the orexin-1 and orexin-2 receptors or as selective antagonists of the orexin-1 receptor, and thus, in particular, in the treatment or prevention of inter alia substance dependence, addiction, anxiety disorders, panic disorders, binge eating, compulsive disorders, impulse control disorders, cognitive impairment and Alzheimer's disease.
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Page/Page column 130
(2019/03/17)
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- Construction of C(sp2)?C(sp3) Bond between Quinoxalin-2(1H)-ones and N-Hydroxyphthalimide Esters via Photocatalytic Decarboxylative Coupling
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A novel visible-light-driven decarboxylative coupling of alkyl N-hydroxyphthalimide esters (NHP esters) with quinoxalin-2(1H)-ones has been developed. This C(sp2)?C(sp3) bond-forming transformation exhibits excellent substrate generality with respect to both the coupling partners. Of note, a series of 3-primary alkyl-substituted quinoxalin-2(1H)-ones that were difficult to synthesize by previous methods could be obtained in moderate to excellent yields. Additionally, the mild conditions, easy availability of substrates, wide functional group tolerance and operational simplicity make this protocol practical in the synthesis of 3-alkylated quinoxalin-2(1H)-ones.
- Yan, Zhiyang,Sun, Bin,Zhang, Xun,Zhuang, Xiaohui,Yang, Jin,Su, Weike,Jin, Can
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p. 3344 - 3349
(2019/09/06)
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- Electrochemical Cross-Coupling of C(sp2)?H with Aryldiazonium Salts via a Paired Electrolysis: an Alternative to Visible Light Photoredox-Based Approach
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Photoredox-based C?H bond functionalization constitutes one of the most powerful and atom-economical approaches to organic syntheses. During this type of reaction, single electron transfer takes place between the photocatalyst (PC) and redox- active substrates. Electrosynthesis also involves electron transfer between substrates and electrodes. In this paper, we focus upon electrochemical cross-coupling of C(sp2)?H with aryldiazonium salts and have developed an efficient electrochemical approach to the Minisci-type arylation reaction. The constant current paired electrosynthesis proceeds in a simple undivided cell without external supporting electrolyte, features a wide range of substrates and is easy to scale-up. These results demonstrate that photoredox-based cross-coupling of C(sp2)?H with aryldiazonium salts can also proceed successfully under paired electrolysis conditions, thereby contributing to understanding of the parallels between photosynthesis and electrosynthesis. (Figure presented.).
- Jiang, Yang-ye,Dou, Gui-yuan,Zhang, Luo-sha,Xu, Kun,Little, R. Daniel,Zeng, Cheng-chu
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supporting information
p. 5170 - 5175
(2019/11/13)
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- Nickel-catalyzed electrochemical reductive decarboxylative coupling of: N -hydroxyphthalimide esters with quinoxalinones
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Herein the first example of electrochemically enabled, NiCl2-catalyzed reductive decarboxylative coupling of N-hydroxyphthalimide (NHP) esters with quinoxalinones is reported. A range of primary, secondary, tertiary aliphatic carboxylic acids and amino acid-derived esters were tolerated well. This decarboxylative coupling allows access to structurally diverse 3-alkylated quinoxalinones in up to 91% yields.
- Lian, Fei,Xu, Kun,Meng, Wei,Zhang, Haonan,Tan, Zhoumei,Zeng, Chengchu
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supporting information
p. 14685 - 14688
(2019/12/11)
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- Electrochemically dehydrogenative C-H/P-H cross-coupling: Effective synthesis of phosphonated quinoxalin-2(1: H)-ones and xanthenes
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An efficient electrochemical approach for the C(sp2)-H phosphonation of quinoxalin-2(1H)-ones and C(sp3)-H phosphonation of xanthenes has been developed. The chemistry was performed in an undivided cell under constant current conditions and features a wide range of substrates, up to 99% yield and it is free of transition-metal catalysts- A nd external oxidants, thereby providing a straightforward approach for dehydrogenative C-H/P-H cross-coupling. In addition, control experiments disclose that some of the reactions may involve a radical pathway.
- Li, Ke-Jing,Jiang, Yang-Ye,Xu, Kun,Zeng, Cheng-Chu,Sun, Bao-Guo
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supporting information
p. 4412 - 4421
(2019/08/21)
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- Diarylureaquinoxaline derivative with antitumor activity and synthesis method thereof
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The invention discloses a diarylureaquinoxaline derivative with antitumor activity and a synthesis method thereof. According to the technical scheme, the diarylureaquinoxaline derivative is a derivative obtained by taking quinoxaline as a matrix and carrying out appropriate structural modification, and concretely, o-phenylenediamine is taken as a starting material and four steps of reactions arecarried out for substitution and further for adding a fluorine atom and diarylurea, so that the diarylureaquinoxaline derivative with antitumor activity is synthesized. The derivative is an importantheterocyclic compound and has good biological activity. The structural formula of the derivative is shown in the description.
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Paragraph 0025; 0027
(2018/06/15)
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- SUBSTITUTED QUINOXALINE DERIVATIVES AS PEST CONTROL AGENT
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The invention relates to novel compounds of the formula (I) in which R1, R2, R3, R4, R5, R6, Y1 and Y2 have the meanings given above, to a plurality of processes and intermediates for their preparation and to their use as acaricides and/or insecticides for controlling animal pests. The compounds of the formula (I) are also suitable as nematicides for plant-damaging pests and/or anthelminthics for endoparasites in humans and animals.
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Paragraph 0442; 0443; 0444; 0445; 0446
(2016/09/06)
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- Discovery of Highly Potent Dual Orexin Receptor Antagonists via a Scaffold-Hopping Approach
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Starting from suvorexant (trade name Belsomra), we successfully identified interesting templates leading to potent dual orexin receptor antagonists (DORAs) via a scaffold-hopping approach. Structure–activity relationship optimization allowed us not only to improve the antagonistic potency on both orexin 1 and orexin 2 receptors (Ox1 and Ox2, respectively), but also to increase metabolic stability in human liver microsomes (HLM), decrease time-dependent inhibition of cytochrome P450 (CYP) 3A4, and decrease P-glycoprotein (Pgp)-mediated efflux. Compound 80 c [{(1S,6R)-3-(6,7-difluoroquinoxalin-2-yl)-3,8-diazabicyclo[4.2.0]octan-8-yl}(4-methyl-[1,1′-biphenyl]-2-yl)methanone] is a potent and selective DORA that inhibits the stimulating effects of orexin peptides OXA and OXB at both Ox1 and Ox2. In calcium-release assays, 80 c was found to exhibit an insurmountable antagonistic profile at both Ox1 and Ox2, while displaying a sleep-promoting effect in rat and dog models, similar to that of the benchmark compound suvorexant.
- Heidmann, Bibia,Gatfield, John,Roch, Catherine,Treiber, Alexander,Tortoioli, Simone,Brotschi, Christine,Williams, Jodi T.,Bolli, Martin H.,Abele, Stefan,Sifferlen, Thierry,Jenck, Fran?ois,Boss, Christoph
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p. 2132 - 2146
(2016/10/25)
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- Fluorine-containing 6,7-dialkoxybiaryl-based inhibitors for phosphodiesterase 10 A: Synthesis and in vitro evaluation of inhibitory potency, selectivity, and metabolism
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Based on the potent phosphodiesterase 10 A (PDE10A) inhibitor PQ-10, we synthesized 32 derivatives to determine relationships between their molecular structure and binding properties. Their roles as potential positron emission tomography (PET) ligands were evaluated, as well as their inhibitory potency toward PDE10A and other PDEs, and their metabolic stability was determined in vitro. According to our findings, halo-alkyl substituents at position 2 of the quinazoline moiety and/or halo-alkyloxy substituents at positions 6 or 7 affect not only the compounds′ affinity, but also their selectivity toward PDE10A. As a result of substituting the methoxy group for a monofluoroethoxy or difluoroethoxy group at position 6 of the quinazoline ring, the selectivity for PDE10A over PDE3A increased. The same result was obtained by 6,7-difluoride substitution on the quinoxaline moiety. Finally, fluorinated compounds (R)-7-(fluoromethoxy)-6-methoxy-4-(3-(quinoxaline-2-yloxy)pyrrolidine-1-yl) quinazoline (16 a), 19 a-d, (R)-tert-butyl-3-(6-fluoroquinoxalin-2-yloxy) pyrrolidine-1-carboxylate (29), and 35 (IC50 PDE10A 11-65 nM) showed the highest inhibitory potential. Further, fluoroethoxy substitution at position 7 of the quinazoline ring improved metabolic stability over that of the lead structure PQ-10. Fluor your health: Phosphodiesterase 10 A (PDE10A) has emerged as an attractive target for the development of 18F-labelled brain imaging agents for positron emission tomography. A series of fluorinated dialkoxybiaryl compounds were synthesized and evaluated as PDE10A inhibitors, assisted by QSAR docking studies. The 7-fluoromethoxy derivative appears to be a promising candidate for further development.
- Schwan, Gregor,Barbar Asskar, Ghadir,Hoefgen, Norbert,Kubicova, Lenka,Funke, Uta,Egerland, Ute,Zahn, Michael,Nieber, Karen,Scheunemann, Matthias,Straeter, Norbert,Brust, Peter,Briel, Detlef
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supporting information
p. 1476 - 1487
(2014/07/21)
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- Substituted diazepan orexin receptor antagonists
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The present invention is directed to substituted diazepan compounds which are antagonists of orexin receptors, and which are useful in the treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which orexin receptors are involved.
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Page/Page column 19
(2008/12/05)
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- DERIVATIVES AND ANALOGS OF N-ETHYLQUINOLONES AND N-ETHYLAZAQUINOLONES
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Bicyclic nitrogen containing compounds and their use as antibacterials.
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Page/Page column 95
(2008/06/13)
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- COMPOUNDS FOR THE TREATMENT OF MULTI-DRUG RESISTANT BACTERIAL INFECTIONS
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The present invention relates to compounds that demonstrate antibacterial activity, processes for their preparation, pharmaceutical compositions containing them as the active ingredient, to their use as medicaments and to their use in the manufacture of medicaments for use in the treatment of bacterial infections in warm-blooded animals such as humans. In particular this invention relates to compounds useful for the treatment of bacterial infections in warm-blooded animals such as humans, more particularly to the use of these compounds in the manufacture of medicaments for use in the treatment of bacterial infections in warm-blooded animals such as humans.
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Page/Page column 136
(2010/11/25)
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- Quinoxaline chemistry. Part XVII. Methyl [4-(substituted 2-quinoxalinyloxy) phenyl] acetates and ethyl N-{[4-(substituted 2-quinoxalinyloxy) phenyl] acetyl} glutamates analogs of methotrexate: Synthesis and evaluation of in vitro anticancer activity
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Fourteen out of 21 quinoxaline derivatives described in the present paper were selected at NCI for evaluation of their in vitro anticancer activity. Preliminary screening showed that some derivatives exhibited a moderate to strong growth inhibition activity on various tumor panel cell lines between 10-5 and 10-4 M concentrations. Interesting selectivities were also recorded between 10-8 and 10-6 M for the compounds 9 and 13.
- Piras, Sandra,Loriga, Mario,Paglietti, Giuseppe
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p. 185 - 194
(2007/10/03)
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