4634-14-4Relevant academic research and scientific papers
Nickel-Catalyzed Reductive 2-Pyridination of Aryl Iodides with Difluoromethyl 2-Pyridyl Sulfone
Miao, Wenjun,Ni, Chuanfa,Xiao, Pan,Jia, Rulong,Zhang, Wei,Hu, Jinbo
, p. 711 - 715 (2021/01/26)
A novel nickel-catalyzed reductive cross-coupling between aryl iodides and difluoromethyl 2-pyridyl sulfone (2-PySO2CF2H) enables C(sp2)-C(sp2) bond formation through selective C(sp2)-S bond cleavage, which demonstrates the new reactivity of 2-PySO2CF2H reagent. This method employs readily available nickel catalyst and sulfones as cross-electrophile coupling partners, providing facile access to biaryls under mild reaction conditions without pregeneration of arylmetal reagents.
Start Selective and Rigidify: The Discovery Path toward a Next Generation of EGFR Tyrosine Kinase Inhibitors
Engelhardt, Harald,B?se, Dietrich,Petronczki, Mark,Scharn, Dirk,Bader, Gerd,Baum, Anke,Bergner, Andreas,Chong, Eugene,D?bel, Sandra,Egger, Georg,Engelhardt, Christian,Ettmayer, Peter,Fuchs, Julian E.,Gerstberger, Thomas,Gonnella, Nina,Grimm, Andreas,Grondal, Elisabeth,Haddad, Nizar,Hopfgartner, Barbara,Kousek, Roland,Krawiec, Mariusz,Kriz, Monika,Lamarre, Lyne,Leung, Joyce,Mayer, Moriz,Patel, Nitinchandra D.,Simov, Biljana Peric,Reeves, Jonathan T.,Schnitzer, Renate,Schrenk, Andreas,Sharps, Bernadette,Solca, Flavio,Stadtmüller, Heinz,Tan, Zhulin,Wunberg, Tobias,Zoephel, Andreas,McConnell, Darryl B.
, p. 10272 - 10293 (2019/11/21)
The epidermal growth factor receptor (EGFR), when carrying an activating mutation like del19 or L858R, acts as an oncogenic driver in a subset of lung tumors. While tumor responses to tyrosine kinase inhibitors (TKIs) are accompanied by marked tumor shrinkage, the response is usually not durable. Most patients relapse within two years of therapy often due to acquisition of an additional mutation in EGFR kinase domain that confers resistance to TKIs. Crucially, oncogenic EGFR harboring both resistance mutations, T790M and C797S, can no longer be inhibited by currently approved EGFR TKIs. Here, we describe the discovery of BI-4020, which is a noncovalent, wild-type EGFR sparing, macrocyclic TKI. BI-4020 potently inhibits the above-described EGFR variants and induces tumor regressions in a cross-resistant EGFRdel19 T790M C797S xenograft model. Key was the identification of a highly selective but moderately potent benzimidazole followed by complete rigidification of the molecule through macrocyclization.
α-Halo carbonyls enable: Meta selective primary, secondary and tertiary C-H alkylations by ruthenium catalysis
Paterson, Andrew J.,Heron, Callum J.,McMullin, Claire L.,Mahon, Mary F.,Press, Neil J.,Frost, Christopher G.
supporting information, p. 5993 - 6000 (2017/07/25)
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.
Direct ortho-Arylation of Pyridinecarboxylic Acids: Overcoming the Deactivating Effect of sp2-Nitrogen
Johnston, Adam J. S.,Ling, Kenneth B.,Sale, David,Lebrasseur, Nathalie,Larrosa, Igor
supporting information, p. 6094 - 6097 (2016/12/09)
Direct arylations of pyridines are challenging transformations due to the high Lewis basicity of the sp2-nitrogen. The use of carboxylates as directing groups is reported, facilitating the Pd-catalyzed C-H arylation of this difficult class of substrates. This methodology allows regioselective C3/C4 arylation, without the need to use solvent quantities of the pyridine, and using low-cost chloro- and bromoarenes as coupling partners. Furthermore, carboxylates could be employed as traceless directing groups through a one-pot C-H arylation/Cu(I)-mediated decarboxylation sequence, thereby accessing directing-group-free pyridine biaryls.
Design and synthesis of non-symmetric phenylpyridine type ligands. Experimental and theoretical studies of their corresponding iridium complexes
Iturbe,Loeb,Barrera,Brito,Ca?ete
, p. 159 - 170 (2016/09/13)
In this work three non-symmetric phenylpyridine type ligands, L1, L2 and L3, were designed, and their corresponding Iridium complexes, C1, C2 and C3, synthetized, in order to understand the effect of ligand asymmetry on the properties of the complexes, and to explore their potentiality in devices. The complexes were structurally characterized by NMR experiments and by X-ray Diffraction, and physicochemically by technics as UV/Vis and cyclic voltammetry. Theoretical DFT calculations of the energy and electronic density of the frontier orbitals of the complexes under study were also performed. The energy of the HOMO and LUMO correlated well with the experimental electrochemical data, and supported the understanding of the processes observed.
Lewis acid-catalyzed borono-minisci reactions of arylboronic acids and heterocycles
Biaco, Joyce L.,Jones, Savannah L.,Barker, Timothy J.
, p. 1687 - 1697 (2016/10/12)
A Lewis acid-catalyzed Minisci reaction between arylboronic acids and heterocycles has been developed. This radical-coupling reaction was demonstrated employing several different heterocycles as well as electron-rich arylboronic acids. Quinoline substrates afforded modest regioselectivity for substitution at the 4-position under the reaction conditions, in contrast to previously reported Br?nsted acid-mediated reactions with quinoline substrates that favored substitution at the 2-position.
Recent developments in the chemistry of heteroaromatic N -oxides
Wang, Youliang,Zhang, Liming
, (2015/02/19)
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.
Scope and limitation for FeSO4-mediated direct arylation of heteroarenes with arylboronic acids and its synthetic applications
Komeyama, Kimihiro,Nagao, Yuya,Abe, Manabu,Takaki, Ken
, p. 301 - 313 (2014/03/21)
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.
Iron-catalyzed direct C-H arylation of heterocycles and quinones with arylboronic acids
Deb, Arghya,Manna, Srimanta,Maji, Arun,Dutta, Uttam,Maiti, Debabrata
supporting information, p. 5251 - 5256 (2013/09/02)
The arylation of C-H bonds to generate heteroaryl-aryl (Het-Ar) and arylated quinone (Quin-Ar) compounds has received great attention to achieve sustainable goals in synthetic chemistry. Despite significant advances, arylation of a broad range of Het-Ar and Quin-Ar derivatives remains a challenging task. Herein, a variety of heterocycles are arylated by using arylboronic acids in the presence of catalytic amounts of inexpensive Fe(NO 3)3. The C-arylated quinone compounds can be prepared by reacting arylboronic acids with either quinone or hydroquinone. The present method is operationally simple, scalable, does not require prefunctionalization of the heterocycle or quinone, and can tolerate a wide variety of functional groups in the coupling partners. These qualities are expected to render this method attractive for academic and industrial use. Direct C-H arylation of a variety of heterocycles and quinones with arylboronic acids has been developed. An inexpensive iron catalyst, Fe(NO3)3, and a co-oxidant, persulfate, were used in air. The protocol is applicable for large-scale synthesis and is expected to find application as a result of its operational simplicity. Copyright
Synthesis and properties of a dendritic FRET donor-acceptor system with cationic iridium(iii) complex core and carbazolyl periphery
Li, Yanfang,Liu, Yang,Zhou, Ming
experimental part, p. 2582 - 2591 (2012/05/04)
In order to enhance the photoluminescence of cyclometalated iridium(iii) complexes, which are potentially useful for biolabeling and bioimaging, a series of benzyl ether branched dendritic moieties with carbazolyl termini were introduced to the cyclometal
