- Cobalt-catalyzed ring-opening addition of azabenzonorbornadienes: Via C(sp3)-H bond activation of 8-methylquinoline
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The first ring-opening addition of a benzylic C(sp3)-H bond to azabenzonorbornadienes is demonstrated. The reaction proceeded under the catalytic system of [Cp?CoI2(CO)], AgSbF6 and Fe(OAc)2 in PhOMe. The methodology showed a good substrate scope with up to 96 yield. The relative configuration of the product was determined as cis-configuration by X-ray crystallography.
- Tan, Heng,Khan, Ruhima,Xu, Dandan,Zhou, Yongyun,Zhang, Xuexin,Shi, Guangrui,Fan, Baomin
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- Cp*Rh(III)-Catalyzed Regioselective C(sp3)-H Methylation of 8-Methylquinolines with Organoborons
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Rh(III)-catalyzed highly regioselective methylation of the unactivated C(sp3)-H bond of 8-methylquinolines with bench stable organoboron reagents is described. A variety of substituted 8-methylquinolines provided the highly regioselective monom
- Kumar, Rakesh,Sharma, Ritika,Kumar, Rohit,Sharma, Upendra
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- Design and development of photoswitchable DFG-Out RET kinase inhibitors
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REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase that is required for development of multiple human tissues, but which is also an important contributor to human cancers. RET activation through rearrangement or point mutations occurs in thyroid and lung cancers. Furthermore, activation of wild type RET is an increasingly recognized mechanism promoting tumor growth and dissemination of a much broader group of cancers. RET is therefore an attractive therapeutic target for small-molecule kinase inhibitors. Non-invasive control of RET signaling with light offers the promise of unveiling its complex spatiotemporal dynamics in vivo. In this work, photoswitchable DFG-out RET kinase inhibitors based on heterocycle-derived azobenzenes were developed, enabling photonic control of RET activity. Based on the binding mode of DFG-out kinase inhibitors and using RET kinase as the test model, we developed a photoswitchable inhibitor with a quinoline “head” constituting the azoheteroarene. This azo compound was further modified by three different strategies to increase the difference in biological activity between the E-isomer and the light enriched Z-isomer. Stilbene-based derivatives were used as model compounds to guide in the selection of substituents that could eventually be introduced to the corresponding azo compounds. The most promising quinoline-based compound showed more than a 15-fold difference in bioactivity between the two isomers in a biochemical assay. However, the same compound showed a decreased Z/E (IC50) ratio in the cellular assay, tentatively assigned to stability issues. The corresponding stilbene compound gave a Z/E (IC50) ratio well above 100, consistent with that measured in the biochemical assay. Ultimately, a 7-azaindole based photoswitchable DFG-out kinase inhibitor was shown to display more than a 10-fold difference in bioactivity between the two isomers, in both a biochemical and a cell-based assay, as well as excellent stability even under reducing conditions.
- Andréasson, Joakim,Andreasson, M?ns,Carrasco, Marta P.,Fleming, Cassandra,Gao, Chunxia,Gr?tli, Morten,H?versen, Liliana,Lundb?ck, Thomas,Xu, Yongjin
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- Non-electronic aromatic ring activation by simple steric repulsion between substituents in 1-methylquinolinium salt systems
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A systematic study of non-electronic activation of an aromatic ring was performed using a series of 8-substituted 1-methylquinolinium salts. As the 8-substituent became bulkier, the quinoline framework was distorted by steric repulsion between substituents at the 1- A nd 8-positions. This was accompanied by lack of coplanarity, which brought about dearomatization. Consequently, quinolinium ions possessing a bulky 8-substituent exhibited high reactivity undergoing nucleophilic addition at the 2-position efficiently. We demonstrate that the activation was achieved sterically and not electronically.
- Iwai, Kento,Yokoyama, Soichi,Asahara, Haruyasu,Nishiwaki, Nagatoshi
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- Cp*RhIII-Catalyzed Sterically Controlled C(sp3)?H Selective Mono- and Diarylation of 8-Methylquinolines with Organoborons
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Herein, the RhIII-catalyzed selective monoarylation and diarylation (symmetrical and unsymmetrical) of 8-methylquinolines with organoboron reagents are disclosed. The selective monoarylation of primary C(sp3)?H bonds is achieved by using 7-substituted 8-methylquinolines or by changing the quantity of the aryl boronic acids. The method is also applicable for the arylation of 2-ethylpyridines, and the heteroarylation with thiophene-2-ylboronic acids. Symmetrical and unsymmetrical diarylation of 8-methylquinolines have been carried out in one-pot and sequential manner, respectively. Late-stage monoarylation of oxime derivatives and gram-scale synthesis of monoarylated products has also been carried out. A mechanistic study revealed that the current reaction is first order with respect to both reactants and a five-membered rhodacycle intermediate may be involved in the catalytic cycle.
- Chandra, Devesh,Dhiman, Ankit Kumar,Gupta, Shiv Shankar,Kumar, Rakesh,Parmar, Diksha,Sharma, Upendra
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supporting information
(2020/03/23)
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- Cobalt-catalysed C–H methylation for late-stage drug diversification
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The magic methyl effect is well acknowledged in medicinal chemistry, but despite its significance, accessing such analogues via derivatization at a late stage remains a pivotal challenge. In an effort to mitigate this major limitation, we here present a strategy for the cobalt-catalysed late-stage C–H methylation of structurally complex drug molecules. Enabling broad applicability, the transformation relies on a boron-based methyl source and takes advantage of inherently present functional groups to guide the C–H activation. The relative reactivity observed for distinct classes of functionalities were determined and the sensitivity of the transformation towards a panel of common functional motifs was tested under various reaction conditions. Without the need for prefunctionalization or postdeprotection, a diverse array of marketed drug molecules and natural products could be methylated in a predictable manner. Subsequent physicochemical and biological testing confirmed the magnitude with which this seemingly minor structural change can affect important drug properties. [Figure not available: see fulltext.]
- Ackermann, Lutz,Friis, Stig D.,Johansson, Magnus J.
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p. 511 - 519
(2020/06/05)
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- Pd-Catalyzed Alkylation of (Iso)quinolines and Arenes: 2-Acylpyridine Compounds as Alkylation Reagents
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The first Pd-catalyzed alkylation of (iso)quinolines and arenes is reported. The readily available and bench-stable 2-acylpyridine compounds were used as an alkylation reagent to form the structurally versatile alkylated (iso)quinolines and arenes. The method affords a convenient pathway for the introduction of alkyl groups into organic molecules.
- Wu, Qingsong,Han, Shuaijun,Ren, Xiaoxiao,Lu, Hongtao,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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supporting information
p. 6345 - 6348
(2018/10/20)
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- Cp?Rh(III)-Catalyzed Mild Addition of C(sp3)-H Bonds to α,β-Unsaturated Aldehydes and Ketones
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A Rh(III)-catalyzed addition of benzylic C(sp3)-H bond to α,β-unsaturated ketones/aldehydes has been realized, leading to efficient synthesis of γ-aryl ketones/aldehydes. This atom-economic reaction proceeded under mild and redox-neutral conditions with a broad substrate scope. Besides benzylic C-H, allylic C-H bonds are also applicable when assisted by O-methyl ketoxime directing groups.
- Liu, Bingxian,Hu, Panjie,Zhou, Xukai,Bai, Dachang,Chang, Junbiao,Li, Xingwei
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supporting information
p. 2086 - 2089
(2017/04/28)
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- Synthesis of quinolines by iron-catalyzed reaction of anilines with propane-1,3-diol
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Quinoline and its derivatives were synthesized by cyclocondensation of anilines with propane-1,3-diol in 57-96% yield in the presence of iron-containing catalysts in carbon tetrachloride.
- Khusnutdinov,Bayguzina,Aminov
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p. 2725 - 2727
(2016/02/18)
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- Reduction of nitroarenes followed by propanol group transfer from tris(3-hydroxypropyl)- amine and cyclization leading to quinolines under heterogeneous Pd-C catalysis
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Nitroarenes having electron-donating or -withdrawing substituents are reduced to anilines and cyclized with tris(3- hydroxypropyl)amine in the presence of a catalytic amount of Pd-C along with tin(II) chloride and isopropanol in dioxane-H2O medium to give the corresponding quinolines in good to excellent yields. Copyright
- Cho, Chan Sik,Kim, Tae Gyun,Yoon, Nam Sik
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experimental part
p. 291 - 293
(2010/08/04)
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- Gold-catalyzed highly regioselective oxidation of C-C triple bonds without acid additives: Propargyl moieties as masked α,β-unsaturated carbonyls
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Gold-catalyzed intermolecular oxidations of internal alkynes have been achieved with high regioselectivities using 8-alkylquinoline N-oxides as oxidants and in the absence of acid additives. Synthetically versatile α,β-unsaturated carbonyls are obtained in good to excellent yields and with excellent E-selectivities. A range of functional groups such as THP, MOMO, N3, OTBS, and N-Boc are tolerated. This reaction allows α,β-unsaturated carbonyls to be masked as propargyl moieties, thus offering a practical solution to compatibility issues with these functional groups likely encountered in syntheses of complex structures.
- Lu, Biao,Li, Chaoqun,Zhang, Liming
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supporting information; experimental part
p. 14070 - 14072
(2011/01/04)
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- QUINOLYNYLMETHYLIMIDIZOLES AS THERAPEUTIC AGENTS
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Disclosed herein are methods for treating a disorder associated with selective subtype modulation of alpha 2B and alpha 2C adrenergic receptors. Such methods can be performed, for example, by administering to a subject in need thereof a pharmaceutical com
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- QUINOLYNYLMETHYLIMIDIZOLES AS THERAPEUTIC AGENTS
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Disclosed herein is a compound of the formula (I): (I). Therapeutic methods, compositions and medicaments related thereto are also disclosed.
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Page/Page column 15
(2008/12/07)
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- TRANSITION METAL-CATALYZED ALKYLATION OF C-H BONDS WITH ORGANOBORON REAGENTS
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One aspect of the present invention relates to methods for functionalization of 2-arylpyridine and arylpyrazoles with organoboron reagents in the presence of a transition metal catalyst to furnish alkylated arylpyridines and arylpyrazoles via regioselective functionalization of sp2 -hybridized C-H bonds at a position ortho to the point of attachment of the pyridine or pyrazole ring to the aromatic nucleus, hi other embodiments, the present invention provides for alkylation of sp3-hybridized C-H bonds in alkylpyridines.
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Page/Page column 9; 62-63; 74
(2008/06/13)
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- Palladium-catalyzed alkylation of sp2 and sp3 C-H bonds with methylboroxine and alkylboronic acids: Two distinct C-H activation pathways
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Palladium-catalyzed alkylations of sp2 and sp3 C-H bonds with either methylboroxine or alkylboronic acids were developed. Ag2O or AgCO3 is used as a crucial oxidant and promoter for the transmetalation step. Ether, ester, alcohol, and alkene functional groups are tolerated. A new C-H activation pathway differing from the cyclometalation process is elucidated using methylboroxine as the coupling partner. Copyright
- Chen, Xiao,Goodhue, Charles E.,Yu, Jin-Quan
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p. 12634 - 12635
(2008/02/05)
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- Rhodium(I) Complexes of 8-Methyl-, 8-Ethyl-, and 8-Isopropyl-quinolines and Realated 2-Substituted Derivatives
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The complexes have been prepared from on adding unidentate L (8-methyl-, -ethyl-, or -isopropyl-quinoline) or bidentate L (1,10-phenantroline or quinoline-2-carboxaldehide-N-methylimine). 8-Alkyl-substitution of the latter ligand gives the complexes as isomers with uni- and bi-dentate L respectively with relative stabilities of the unidentate form depending on the 8-substituent in the order Pri > Et > Me.Unidentate L is also favoured by replacing PPh3 by P(C6H11)3 but bidentate co-ordination is found using AsPh3 or PMe2Ph.Equilibrium constants for chloro-bridge cleavage of by 8-substituted and 2,8-disubstituted quinolines are reduced by increasing the size of the 8-susbtituent and even more by further introduction of a 2-methyl group.The contributions of distortions in the co-ordination to these changes in equilibrium constants are discussed.
- Deeming, Antony J.,Rothwell, Ian P.
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p. 1259 - 1264
(2007/10/02)
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