- Deaminative chlorination of aminoheterocycles
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Selective modification of heteroatom-containing aromatic structures is in high demand as it permits rapid evaluation of molecular complexity in advanced intermediates. Inspired by the selectivity of deaminases in nature, herein we present a simple methodology that enables the NH2 groups in aminoheterocycles to be conceived as masked modification handles. With the aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)?NH2 can be converted into C(sp2)?Cl bonds. The method is characterized by its wide functional group tolerance and substrate scope, allowing the modification of >20 different classes of heteroaromatic motifs (five- and six-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH2 into Cl in a late-stage fashion enables practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals or highly oxidizing and unselective chlorinating agents. [Figure not available: see fulltext.]
- Ghiazza, Clément,Faber, Teresa,Gómez-Palomino, Alejandro,Cornella, Josep
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- Discovery of 9,10-dihydrophenanthrene derivatives as SARS-CoV-2 3CLpro inhibitors for treating COVID-19
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The epidemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has now spread worldwide and efficacious therapeutics are urgently needed. 3-Chymotrypsin-like cysteine protease (3CLpro) is an indispensable protein in viral replication and represents an attractive drug target for fighting COVID-19. Herein, we report the discovery of 9,10-dihydrophenanthrene derivatives as non-peptidomimetic and non-covalent inhibitors of the SARS-CoV-2 3CLpro. The structure-activity relationships of 9,10-dihydrophenanthrenes as SARS-CoV-2 3CLpro inhibitors have carefully been investigated and discussed in this study. Among all tested 9,10-dihydrophenanthrene derivatives, C1 and C2 display the most potent SARS-CoV-2 3CLpro inhibition activity, with IC50 values of 1.55 ± 0.21 μM and 1.81 ± 0.17 μM, respectively. Further enzyme kinetics assays show that these two compounds dose-dependently inhibit SARS-CoV-2 3CLpro via a mixed-inhibition manner. Molecular docking simulations reveal the binding modes of C1 in the dimer interface and substrate-binding pocket of the target. In addition, C1 shows outstanding metabolic stability in the gastrointestinal tract, human plasma, and human liver microsome, suggesting that this agent has the potential to be developed as an orally administrated SARS-CoV-2 3CLpro inhibitor.
- Zhang, Jian-Wei,Xiong, Yuan,Wang, Feng,Zhang, Fu-Mao,Yang, Xiaodi,Lin, Guo-Qiang,Tian, Ping,Ge, Guangbo,Gao, Dingding
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- Selective Halogenation of Pyridines Using Designed Phosphine Reagents
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Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochemicals, and ligands for metal complexes, but strategies to selectively halogenate pyridine C-H precursors are lacking. We designed a set of heterocyclic phosphines that are installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. Computational studies indicate that C-halogen bond formation occurs via an SNAr pathway, and phosphine elimination is the rate-determining step. Steric interactions during C-P bond cleavage account for differences in reactivity between 2- and 3-substituted pyridines.
- Alegre-Requena, Juan V.,Levy, Jeffrey N.,Liu, Renrong,McNally, Andrew,Paton, Robert S.
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supporting information
p. 11295 - 11305
(2020/07/13)
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- Palladium-catalyzed c-4 selective coupling of 2,4-dichloropyridines and synthesis of pyridine-based dyes for live-cell imaging
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An alternative process of Pd-catalyzed C-4 selective coupling of 2,4-dichloropyridines with boronic esters was developed, which afforded 24 examples of C-4 coupled pyridines in moderate to good yields. After further arylation, 21 examples of C-2, C-4 diarylated pyridines with a significant photophysical property were obtained, which were applied as pyridine-based dyes into live-cell imaging with good biocompatibility and low toxicity.
- Chen, Jing,Ding, Yechun,He, Chen,Hu, Xin,Huang, Qitong,Kuang, Ying,Liu, Jinbiao,Yang, Min
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p. 6498 - 6508
(2020/06/09)
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- Small organic molecules with tailored structures: Initiators in the transition-metal-free C-H arylation of unactivated arenes
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Simple, small organic molecules containing nitrogen and oxygen atoms in their structures have been disclosed to catalyze transition-metal-free C-H arylation of unactivated arenes with aryl iodides in the presence of tBuOK. In this article, an optimized catalytically active molecule, (2-(methylamino)phenyl)methanol, was designed. A broad range of aryl iodides could be converted into the corresponding arylated products at 100 °C over 24 h with good to excellent yields. Mechanistic experiments verified that radicals participated in this catalytic transformation and that the cleavage of the aromatic C-H bond was not the rate determining step. A K+ capture experiment by 18-crown-6 emphasized the significance of the cation species of the strong base. Fourier transform infrared spectroscopy proved that the catalytic system was activated by the hydrogen bonds between small organic molecules and tBuOK. Also, a clear mechanism was proposed. This transition-metal-free method affords a promising system for efficient and inexpensive synthesis of biaryls via a user-friendly approach, as confirmed by scale-up experiments.
- Chen, Suqing,Chen, Wenjun,Chen, Yu,Liu, Zhenghui,Mu, Tiancheng,Wang, Peng,Yan, Zhenzhong
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p. 14500 - 14509
(2020/04/27)
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- Red to blue emitting cationic iridium complexes with 2-phenyl-4-dimethylaminopyridine as the cyclometalating ligand: Synthesis, characterization and electroluminescent devices
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2-Phenyl-4-dimethylaminopyridine (dmappy) with high 3π-π? triplet energy is, for the first time, employed as the cyclometalating ligand for constructing cationic iridium complexes with tunable emission properties. Three complexes, na
- Meng, Xianwen,Bai, Rubing,Wang, Xiaoxiang,Pan, FangFang,He, Lei
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p. 458 - 466
(2019/03/13)
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- C6-Selective Direct Arylation of 2-Phenylpyridine via an Activated N-methylpyridinium Salt: A Combined Experimental and Theoretical Study
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An elegant pre-activation strategy, based on the formation of N-methylpyridinium iodide salts for C6-selective direct arylation of 2-phenylpyridines using Pd/Cu cooperative catalysis, has been developed. By this methodology, a wide range of unsymmetrical 2, 6-diarylpyridines were synthesized with high reactivity and regioselectivity as well as good functional group tolerance. In particular, challenging substrates bearing electron donating groups (EDGs), such as OMe, NMe2, were also successfully employed in this reaction. Deuterium incorporation studies revealed that the C?H bond acidity is improved significantly in N-methylpyridinium salts compared with their N-Oxide and N-iminopyridinium ylide counterparts, thus solving the long-standing problem associated with previous strategies for the synthesis of diaryl pyridines. Finally, the control experiments and DFT calculations supported a Pd-catalyzed and Cu-mediated mechanism in which a carbenoid copper species that is formed in-situ from N-methylpyridinium salts, participates in a Pd-catalyzed arylation followed by an iodide-promoted N-demethylation process. (Figure presented.).
- Yin, Changzhen,Zhong, Kangbao,Li, Wenjing,Yang, Xiao,Sun, Rui,Zhang, Chunchun,Zheng, Xueli,Yuan, Maolin,Li, Ruixiang,Lan, Yu,Fu, Haiyan,Chen, Hua
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supporting information
p. 3990 - 3998
(2018/09/12)
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- Transition-Metal-Free Decarboxylative Arylation of 2-Picolinic Acids with Arenes under Air Conditions
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A facile, transition-metal-free, and direct decarboxylative arylation of 2-picolinic acids with simple arenes is described. The oxidative decarboxylative arylation of 2-picolinic acids with arenes proceeds readily via N-chloro carbene intermediates to afford 2-arylpyridines in satisfactory to good yields under transition-metal-free conditions. This new type of decarboxylative arylation is operationally simple and scalable and exhibits high functional-group tolerance. Various synthetically useful functional groups, such as halogen atoms, methoxycarbonyl, and nitro, remain intact during the decarboxylative arylation of 2-picolinic acids.
- Zhang, Xitao,Feng, Xiujuan,Zhou, Chuancheng,Yu, Xiaoqiang,Yamamoto, Yoshinori,Bao, Ming
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supporting information
p. 7095 - 7099
(2018/11/23)
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- ORGANOMETALLIC COMPLEX, LIGHT-EMITTING ELEMENT, LIGHT-EMITTING DEVICE, ELECTRONIC APPARATUS, AND LIGHTING DEVICE
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PROBLEM TO BE SOLVED: To provide a novel organometallic complex that emits phosphorescence with high color purity. SOLUTION: An organometallic complex, represented by general formula (G1), comprises iridium and a plurality of ligands each having a 2-phenylpyridine skeleton. In the organometallic complex, one or two of the ligands have a carbazole skeleton at a 4-position of the 2-phenylpyridine skeleton. (R1 to R8 and R9 to R23 are an alkyl group, an aryl group or the like). SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
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Paragraph 0304; 0306; 0307
(2018/05/09)
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- Non-transition metal-catalyzed 2-phenylpyridine compound synthesis method
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The invention relates to a pharmaceutical and chemical intermediate preparation method, in particular to a non-transition metal-catalyzed 2-phenylpyridine compound synthesis method. A 2-phenylpyridine compound serves as an important component of a plurality of pharmacologically active molecules and bioactive molecules, has important application value in the fields of organic synthesis, pharmaceutical chemistry and the like, and is broad in market prospect. According to the non-transition metal-catalyzed 2-phenylpyridine compound synthesis method, namely a non-transition metal-catalyzed 2-phenylpyridine derivative synthesis method, pyridine-2-formic acid and benzene are adopted as raw materials; and under the presence of one or more alkalis and free radical initiators, the 2-phenylpyridine compound is synthesized in the mild condition. The non-transition metal-catalyzed 2-phenylpyridine compound synthesis method provided by the invention has the advantages that the steps are simple, the raw materials are easy to obtain, the reaction condition is mild, as well as the use value and the social and economic benefits are relatively great.
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Paragraph 0040; 0041; 0042
(2017/07/04)
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- α-Halo carbonyls enable: Meta selective primary, secondary and tertiary C-H alkylations by ruthenium catalysis
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A catalytic meta selective C-H alkylation of arenes is described using a wide range of α-halo carbonyls as coupling partners. Previously unreported primary alkylations with high meta selectivity have been enabled by this methodology whereas using straight chain alkyl halides affords ortho substituted products. Mechanistic analysis reveals an activation pathway whereby cyclometalation with a ruthenium(ii) complex activates the substrate molecule and is responsible for the meta selectivity observed. A distinct second activation of the coupling partner allows site selective reaction between both components.
- Paterson, Andrew J.,Heron, Callum J.,McMullin, Claire L.,Mahon, Mary F.,Press, Neil J.,Frost, Christopher G.
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supporting information
p. 5993 - 6000
(2017/07/25)
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- Modular synthesis of simple cycloruthenated complexes with state-of-the-art performance in p-type DSCs
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A modular approach based on Suzuki-Miyaura cross coupling and Miyaura borylation has been used to prepare two cyclometallated [Ru(N N)2(C N)]+ complexes which possess either a carboxylic or phosphonic acid group attached via a phenylene spacer to the 4-position of the pyridine ring in the C N ligand. The key intermediate in the synthetic pathway is [Ru(bpy)2(1)]+ where bpy = 2,2′-bipyridine and H1 is 4-chloro-2-phenylpyridine. The crystal structure of [Ru(bpy)2(1)][PF6] is presented. Reaction of [Ru(bpy)2(1)][PF6] with 4-carboxyphenylboronic acid leads to [Ru(bpy)2(H6)][PF6], while the phosphonic acid analogue is isolated as the zwitterion [Ru(bpy)2(H5)]. The cyclometallated complexes have been characterized by mass spectrometry, multinuclear NMR spectroscopy, absorption spectroscopy and electrochemistry. [Ru(bpy)2(5)] adsorbs onto NiO FTO/NiO electrodes (confirmed by solid-state absorption spectroscopy) and its performance in p-type dye-sensitized solar cells (DSCs) has been compared to that of the standard dye P1; two-screen printed layers of NiO give better DSC performances than one layer. Duplicate DSCs containing [Ru(bpy)2(H5)] achieve short-circuit current densities (JSC) of 3.38 and 3.34 mA cm-2 and photoconversion efficiencies (η) of 0.116 and 0.109%, respectively, compared to values of JSC = 1.84 and 1.96 mA cm-2 and η = 0.057 and 0.051% for P1. Despite its simple dye structure, the performance of [Ru(bpy)2(H5)] parallels the best-performing cyclometallated ruthenium(ii) dye in p-type DSCs reported previously (He et al., J. Phys. Chem. C, 2014, 118, 16518) and confirms the effectiveness of a phosphonic acid anchor in the dye and the attachment of the anchoring unit to the pyridine (rather than phenyl) ring of the cyclometallating ligand.
- Brunner, Felix,Marinakis, Nathalie,Wobill, Cedric,Willgert, Markus,Ertl, Cathrin D.,Kosmalski, Tatjana,Neuburger, Markus,Bozic-Weber, Biljana,Glatzel, Thilo,Constable, Edwin C.,Housecroft, Catherine E.
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p. 9823 - 9833
(2016/11/02)
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- HETEROLEPTIC IRIDIUM COMPLEXES AS DOPANTS
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Novel phosphorescent heteroleptic iridium complexes with phenylpyridine and dibenzo-containing ligands are provided. Alkyl substitution at specific positions on the ligands gives rise to compounds with improved OLED properties, including saturated green emission.
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Page/Page column 93
(2016/10/27)
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- Recent developments in the chemistry of heteroaromatic N -oxides
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Selected developments in the chemistry of heteroaromatic N-oxides since 2001 are presented in this review. The use of these N-oxides, both in late-transition-metal-catalyzed oxidations of carbon-carbon triple bonds and in regioselective C-H functionalizations of the heteroarene, are contemporary topics of interest and the focus of the discussion. 1 Introduction 2 Synthesis of Heteroaromatic N-Oxides 2.1 Direct Oxidation of Hindered Heteroarenes 2.2 Through Construction of Heteroaromatic Rings 3 Heteroaromatic N-Oxides as Oxidants 3.1 Alkyne Oxidation 3.2 Allene Oxidation 3.3 Carbene Oxidation 4 Heteroaromatic N-Oxides as Substrates 4.1 Deoxygenative ortho-C-H Functionalization with Prior Activation 4.2 Deoxygenative ortho-C-H Functionalization with Nonstabilized Carbanions 4.3 Nondeoxygenative C-H Functionalization 4.3.1 ortho-C-H Functionalization 4.3.2 N-Oxide Directed ortho-Alkyl C-H Functionalization 4.3.3 N-Oxide Directed Remote C-H Functionalization 4.4 1,3-Dipolar Cycloaddition 5 Conclusion and Outlook.
- Wang, Youliang,Zhang, Liming
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- Chemoselective chromium(II)-catalyzed cross-coupling reactions of dichlorinated heteroaromatics with functionalized aryl Grignard reagents
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Chromium(II) chloride catalyzes the chemoselective cross-coupling reaction of dichloropyridines with a range of functionalized (hetero)aromatic Grignard reagents at room temperature. Functional groups, such as esters and acetals, are well tolerated in this transformation. Previously challenging substrates, quinolines and isoquinolines, participate in the selective Cr-catalyzed cross-coupling in cyclopentyl methyl ether (CPME) as the solvent. The effective purging of Cr salts is demonstrated by using various solid supports.
- Steib, Andreas K.,Kuzmina, Olesya M.,Fernandez, Sarah,Malhotra, Sushant,Knochel, Paul
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supporting information
p. 1961 - 1965
(2015/01/30)
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- Cross-coupling study of iodo/chloropyridines and 2-chloroquinoline with atom-economic triarylbismuth reagents under Pd-catalysis
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This study describes the palladium-catalyzed couplings of iodopyridines, chloropyridines, and chloroquinoline with atom-economic BiAr3 reagents in sub-stoichiometric loadings. Mono-arylations of iodo and chloropyridines produced arylpyridines i
- Rao, Maddali L.N.,Dhanorkar, Ritesh J.
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p. 338 - 349
(2015/03/04)
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- PHOSPHORESCENT MATERIALS
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Novel organic compounds containing a twisted aryl group are provided. In particular, the compounds provided contain a 2-phenylpyridine ligand having a twisted aryl group on the pyridine portion of the ligand. The compounds may be used in organic light emitting devices, particularly as emitting dopants. Devices comprising the compounds containing twisted aryl may demonstrate improved color, efficiency, stability and manufacturing. Additionally, methods are provided for making homoleptic Ir (III) compounds which may contain a twisted aryl.
- -
-
Paragraph 0239; 0240
(2015/11/16)
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- Scope and limitation for FeSO4-mediated direct arylation of heteroarenes with arylboronic acids and its synthetic applications
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FeSO4-mediated direct arylation of heteroarenes with arylboronic acids in the presence of K2S2O8 has been developed. A slow addition of an aqueous solution of an iron complex was crucial in the arylation. Scope and limitation of the heteroarenes and arylboronic acids are discussed. Furthermore, the direct arylation was applied to the formal total synthesis botryllazine B and sodium channel inhibitor.
- Komeyama, Kimihiro,Nagao, Yuya,Abe, Manabu,Takaki, Ken
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p. 301 - 313
(2014/03/21)
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- Ligand-dependent site-selective suzuki cross-coupling of 3,5-dichloropyridazines
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General methods for the highly site-selective Suzuki monocoupling of 3,5-dichloropyridazines have been discovered. By changing the ligand employed, the preferred coupling site can be switched from the 3-position to the 5-position, typically considered the less reactive C-X bond. These conditions are applicable to the coupling of a wide variety of aryl-, heteroaryl-, and vinylboronic acids with high selectivities, thus enabling the rapid construction of diverse arrays of diarylpyradazines in a modular fashion.
- Dai, Xing,Chen, Yonggang,Garrell, Stephanie,Liu, Hong,Zhang, Li-Kang,Palani, Anandan,Hughes, Gregory,Nargund, Ravi
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p. 7758 - 7763
(2013/09/02)
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- Iron-catalyzed cross-coupling of electron-deficient heterocycles and quinone with organoboron species via innate C-H functionalization: Application in total synthesis of pyrazine alkaloid botryllazine A
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Here, we report an iron-catalyzed cross-coupling reaction of electron-deficient heterocycles and quinone with organoboron species via innate C-H functionalization. Iron(II) acetylacetonate along with oxidant (K 2S2O8) and phase-transfer catalyst (TBAB) under open flask conditions efficiently catalyzed the cross-coupling of pyrazine with arylboronic acids and gave monoarylated products in good to excellent yields. Optimized conditions also worked for other heterocylces such as quinoxalines, pyridines, quinoline, and isoquinoline as well as quinones. In addition, we demonstrated as a first example its application for the synthesis of anticancer marine pyrazine alkaloid botryllazine A.
- Singh, Parvinder Pal,Aithagani, Sravan Kumar,Yadav, Mahipal,Singh, Varun Pratap,Vishwakarma, Ram A.
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p. 2639 - 2648
(2013/04/24)
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- HETEROLEPTIC IRIDIUM COMPLEXES AS DOPANTS
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Novel phosphorescent heteroleptic iridium complexes with phenylpyridine and dibenzo-containing ligands are provided. Alkyl substitution at specific positions on the ligands gives rise to compounds with improved OLED properties, including saturated green emission.
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Page/Page column
(2013/03/26)
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- GREEN LUMINESCENT MATERIALS
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There is provided a compound having Formula I In the formula: R1 can be aryl, alkyl, silyl, or deuterated analogs thereof; R2 can be aryl, alkyl, silyl, or deuterated analogs thereof; R3 can be H, D, alkyl, silyl, deuterat
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Page/Page column 31; 32
(2013/10/08)
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- HIGH EFFICIENCY YELLOW EMITTERS FOR OLED APPLICATIONS
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Novel heteroleptic iridium complexes are described. These iridium compounds contain alkyl substituted phenylpyridine ligands, which provide these compounds with beneficial properties when the iridium complexes are incorporated into OLED devices.
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Page/Page column 59
(2012/12/13)
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- Efficient, mild and completely regioselective synthesis of substituted pyridines
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Addition of Grignard reagents to pyridine N-oxides in THF at low temperature (-78 to -20 °C) and treatment with TFAA provides an efficient general procedure for synthesis of substituted pyridines. The method is compatible with a range of functional groups such as esters, halogens and nitriles.
- Andersson, Hans,Sainte-Luce Banchelin, Thomas,Das, Sajal,Olsson, Roger,Almqvist, Fredrik
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supporting information; experimental part
p. 3384 - 3386
(2010/07/06)
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- Synthesis of 2-substituted pyridines via a regiospecific alkylation, alkynylation, and arylation of pyridine N-oxides
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Figure presented Sequential addition of Grignard reagents to pyridine N-oxides in THF at room temperature followed by treatment with acetic anhydride at 120°C afforded 2-substituted pyridines in good to high yields. Furthermore, by exchanging acetic anhydride for DMF in the second step, 2-substituted pyridine N-oxides were obtained, as intermediates suitable for addition of a second Grignard reagent for the synthesis of 2,6-disubstituted pyridines.
- Andersson, Hans,Almqvist, Fredrik,Olsson, Roger
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p. 1335 - 1337
(2008/01/03)
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- Thiazoles and thiopyridines: Novel series of high affinity h5HT 7 ligands
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A series of thiazole based 5HT7 ligands has been identified from screening. Optimisation of the pendent aryl group and modification of the core gave a related series of high affinity, selective thiopyridine based 5HT7 ligands, the most active of which behaves as a partial agonist.
- Thomson, Christopher G.,Beer, Margaret S.,Curtis, Neil R.,Diggle, Helen J.,Handford, Emma,Kulagowski, Janusz J.
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p. 677 - 680
(2007/10/03)
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