- Electro-reductive C-H cyanoalkylation of quinoxalin-2(1H)-ones
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Herein, we report a practical electro-reductive protocol for the direct C–H cyanoalkylation of quinoxalin-2(1H)-ones via iminyl radical-mediated ring opening. These mild reactions proceed under metal-, reductant-, and reagent-free conditions to provide synthetically useful cyanoalkylated quinoxalin-2(1H)-ones.
- Ding, Ling,Liu, Yuxiu,Niu, Kaikai,Wang, Qingmin
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supporting information
(2022/01/24)
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- Synthesis of (E)-Quinoxalinone Oximes through a Multicomponent Reaction under Mild Conditions
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Herein, a novel method for the gram-scale synthesis of (E)-quinoxalinone oximes through a multicomponent reaction under mild conditions is described. Such a transformation was performed under transition-metal-free conditions, affording (E)-oximes in a moderate-to-good yield through recrystallization. Our methodology demonstrates a successful combination of a Mannich-type reaction and radical coupling, providing a green and practical approach for the synthesis of potentially bioactive quinoxalinone-containing molecules.
- Xu, Jun,Yang, Huiyong,He, Lei,Huang, Lin,Shen, Jiabin,Li, Wanmei,Zhang, Pengfei
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supporting information
p. 195 - 201
(2021/01/13)
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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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- 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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- 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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p. 11905 - 11914
(2021/08/24)
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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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- 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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- Persulfate-promoted oxidative C-N bond coupling of quinoxalinones and: NH -sulfoximines
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The persulfate-meditated oxidative C-N bond coupling of the C-H bond of quinoxalinones and the N-H bond of NH-sulfoximines is reported. The reaction proceeds smoothly under transition metal-free conditions and provides good to excellent yields of sulfoximidoyl-functionalized quinoxalinone products under mild conditions. The optimized conditions were found to be suitable for a range of sulfoximine and quinoxalinone substrates. This reaction offers a new and convenient strategy to directly install the sulfoximine moiety into the C3 position of quinoxalinone.
- Sumunnee, Ladawan,Pimpasri, Chaleena,Noikham, Medena,Yotphan, Sirilata
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supporting information
p. 2697 - 2704
(2018/04/27)
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- Rationalization of benzazole-2-carboxylate versus benzazine-3-one/ benzazine-2,3-dione selectivity switch during cyclocondensation of 2-aminothiophenols/phenols/anilines with 1,2-biselectrophiles in aqueous medium
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The cyclocondensation reaction of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyoxalate and diethyl oxalate in aqueous medium leads to the formation of benzothiazole-2-carboxylates via the 5-endo-trig process contrary to Baldwin's rule. On the other hand, the reaction of 2-aminophenols/anilines produced the corresponding benzazine-3-ones or benzazine-2,3-diones via the 6-exo-trig process in compliance with Baldwin's rule. The mechanistic insights of these cyclocondensation reactions using the hard-soft acid-base principle, quantum chemical calculations (density functional theory), and orbital interaction studies rationalize the selectivity switch of benzothiazole-2-carboxylates versus benzazine-3-ones/ benzazine-2,3-diones. The presence of water facilitates these cyclocondensation reactions by lowering of the energy barrier.
- Dhameliya, Tejas M.,Chourasiya, Sumit S.,Mishra, Eshan,Jadhavar, Pradeep S.,Bharatam, Prasad V.,Chakraborti, Asit K.
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p. 10077 - 10091
(2018/05/31)
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- HETEROCYCLIC COMPOUNDS
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The present invention provides a compound represented by the formula (I) wherein each symbol is as defined in the specification, or a salt thereof has an BET family protein inhibitory action, and is useful as an agent for the prophylaxis or treatment of autoimmune diseases and/or inflammatory diseases (e.g., rheumatoid arthritis, multiple sclerosis, idiopathic pulmonary fibrosis, psoriasis, atopic dermatitis, inflammatory bowel disease, Sjogren's syndrome, Behcet's disease, systemic lupus erythematosus etc.), cancer and the like.
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Paragraph 0287
(2016/12/26)
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- The discovery of potent nonstructural protein 5A (NS5A) inhibitors with a unique resistance profile - Part 1
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Nonstructural protein 5A (NS5A) represents a novel target for the treatment of hepatitis C virus (HCV). Daclatasvir, recently reported by Bristol-Myers-Squibb, is a potent NS5A inhibitor currently under investigation in phase 3 clinical trials. While the performance of daclatasvir has been impressive, the emergence of resistance could prove problematic and as such, improved analogues are being sought. By varying the biphenyl-imidazole unit of daclatasvir, novel inhibitors of HCV NS5A were identified with an improved resistance profile against mutant strains of the virus while retaining the picomolar potency of daclatasvir. One compound in particular, methyl ((S)-1-((S)-2-(4-(4-(6-(2-((S)-1-((methoxycarbonyl)-L-valyl)pyrrolidin-2-yl) -1H-imidazol-5-yl)quinoxalin-2-yl)phenyl)-1H-imidazol-2-yl)pyrrolidin-1-yl) -3-methyl-1-oxobutan-2-yl)carbamate (17), exhibited very promising activity and showed good absorption and a long predicted human pharmacokinetic half-life. This compound represents a promising lead that warrants further evaluation. Resisting resistance: An investigation into the anti-hepatitis C virus (HCV) replicon activity of a series of biaryl-linked pyrrolidine NS5A inhibitors explored a diverse range of core structure modifications as key determinants of antiviral activity and susceptibility to common resistance mutations. Further evaluation of several core structure designs identified a compound with excellent pharmacokinetics, suitable for once daily dosing.
- Tran, Thien Duc,Wakenhut, Florian,Pickford, Chris,Shaw, Stephen,Westby, Mike,Smith-Burchnell, Caroline,Watson, Lesa,Paradowski, Michael,Milbank, Jared,Brimage, Rebecca A.,Halstead, Rebecca,Glen, Rebecca,Wilson, Craig P.,Adam, Fiona,Hay, Duncan,Chiva, Jean-Yves,Nichols, Carly,Blakemore, David C.,Gardner, Iain,Dayal, Satish,Pike, Andrew,Webster, Rob,Pryde, David C.
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p. 1378 - 1386
(2014/07/21)
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- HEPATITIS C VIRUS INHIBITORS
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The present invention relates to compounds of the formula (I) and pharmaceutically acceptable salts thereof, to compositions containing such compounds and to the use of such compounds as inhibitors of HCV replication.
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Page/Page column 106
(2011/02/24)
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- SUBSTITUTED BENZOTRIAZINES AND QUINOXALINES AS INHIBITORS OF P7OS6 KINASE
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The invention provides compounds of the formula (1): or salts or tautomers thereof; wherein X1 is N or N+(O ); X2 is N or CH; Q is a C1-3 alkylene group; R1 is selected from hydrogen, C1-4 hydrocarbyl and hydroxy-C2-4 hydrocarbyl; R2, R3 and R4 are the same or different and each is selected from hydrogen, fluorine, chlorine and methyl; Ar1 is an optionally substituted monocyclic 5 or 6-membered aryl or heteroaryl ring containing 0, 1 or 2 heteroatom ring members selected from O, N and S, or a naphthyl ring and Ar2 is an optionally substituted monocyclic 5 or 6-membered heteroaryl ring containing 1, 2 or 3 heteroatom ring members selected from O, N and S. The compounds of formula (1) are inhibitors of p70S6 kinase and are useful in the treatment of proliferative diseases.
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Page/Page column 46; 47
(2010/12/26)
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- ANTI-INFECTIVE PYRIMIDINES AND USES THEREOF
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This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
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Page/Page column 185
(2009/04/25)
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- TRICYCLIC INHIBITORS OF 5-LIPOXYGENASE
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Described herein are compounds and pharmaceutical compositions containing such compounds, which inhibit the activity of 5-lipoxygenase (5-LO). Also described herein are methods of using such 5-LO inhibitors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions, diseases, or disorders.
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Page/Page column 84
(2010/11/28)
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- The facile one pot synthesis of 6-substituted 2(1H)-quinoxalinones
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Facile one pot synthesis of 6-substituted 2(1H)-quinoxalinones and these reaction mechanisms are described.The intramolecular cyclization reaction of 4'-substituted 2'-nitroacetoacetanilides in aqueous basic medium and the reduction of 6-substituted 2(1H)-quinoxalinone-4-oxide wit sodium borohydride or sodium hydrogensulfite were studied in detail
- Sakata, Gozyo,Makino, Kenzi,Morimoto, Katsushi
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p. 143 - 151
(2007/10/02)
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