- Pd-Catalyzed ipso, meta-Dimethylation of ortho-Substituted Iodoarenes via a Base-Controlled C-H Activation Cascade with Dimethyl Carbonate as the Methyl Source
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A methyl group can have a profound impact on the pharmacological properties of organic molecules. Hence, developing methylation methods and methylating reagents is essential in medicinal chemistry. We report a palladium-catalyzed dimethylation reaction of ortho-substituted iodoarenes using dimethyl carbonate as a methyl source. In the presence of K2CO3 as a base, iodoarenes are dimethylated at the ipso- and meta-positions of the iodo group, which represents a novel strategy for meta-C-H methylation. With KOAc as the base, subsequent oxidative C(sp3)-H/C(sp3)-H coupling occurs; in this case, the overall transformation achieves triple C-H activation to form three new C-C bonds. These reactions allow expedient access to 2,6-dimethylated phenols, 2,3-dihydrobenzofurans, and indanes, which are ubiquitous structural motifs and essential synthetic intermediates of biologically and pharmacologically active compounds.
- Wu, Zhuo,Wei, Feng,Wan, Bin,Zhang, Yanghui
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supporting information
p. 4524 - 4530
(2021/05/04)
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- NEW COMPOUND HAVING FGFR INHIBITORY ACTIVITY AND PREPARATION AND APPLICATION THEREOF
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The present invention relates to a new compound having an FGFR inhibitory activity and preparation and application thereof. In particular, the compound according to the present invention has a structure as shown in formula I, wherein each group and substituent are as defined in the description. Also disclosed in the present invention are a preparation method for the compound and a use thereof in preparation of a drug for treating and/or preventing a tumor-related disease and/or an FGFR-related disease.
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- Decarboxylative Suzuki-Miyaura coupling of (hetero)aromatic carboxylic acids using iodine as the terminal oxidant
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A novel methodology for the decarboxylative Suzuki-Miyaura-type coupling has been established. This process uses iodine or a bromine source as both the decarboxylation mediator and the terminal oxidant, thus avoiding the need for stoichiometric amounts of transition metal salts previously required. Our new protocol allows for the construction of valuable biaryl architectures through the coupling of (hetero)aromatic carboxylic acids with arylboronic acids. The scope of this decarboxylative Suzuki reaction has been greatly diversified, allowing for previously inaccessible non-ortho-substituted aromatic acids to undergo this transformation. The procedure also benefits from low catalyst loadings and the absence of stoichiometric transition metal additives.
- Quibell, Jacob M.,Duan, Guojian,Perry, Gregory J.P.,Larrosa, Igor
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supporting information
p. 6445 - 6448
(2019/06/07)
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- Transition-Metal-Free Decarboxylative Iodination: New Routes for Decarboxylative Oxidative Cross-Couplings
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Constructing products of high synthetic value from inexpensive and abundant starting materials is of great importance. Aryl iodides are essential building blocks for the synthesis of functional molecules, and efficient methods for their synthesis from chemical feedstocks are highly sought after. Here we report a low-cost decarboxylative iodination that occurs simply from readily available benzoic acids and I2. The reaction is scalable and the scope and robustness of the reaction is thoroughly examined. Mechanistic studies suggest that this reaction does not proceed via a radical mechanism, which is in contrast to classical Hunsdiecker-type decarboxylative halogenations. In addition, DFT studies allow comparisons to be made between our procedure and current transition-metal-catalyzed decarboxylations. The utility of this procedure is demonstrated in its application to oxidative cross-couplings of aromatics via decarboxylative/C-H or double decarboxylative activations that use I2 as the terminal oxidant. This strategy allows the preparation of biaryls previously inaccessible via decarboxylative methods and holds other advantages over existing decarboxylative oxidative couplings, as stoichiometric transition metals are avoided.
- Perry, Gregory J. P.,Quibell, Jacob M.,Panigrahi, Adyasha,Larrosa, Igor
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supporting information
p. 11527 - 11536
(2017/08/30)
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- Mild and selective organocatalytic iodination of activated aromatic compounds
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We describe an organocatalytic iodination of activated aromatic compounds using 1,3-diiodo-5,5-dimethylhydantoin (DIH) as the iodine source with thiourea catalysts in acetonitrile. The protocol is applicable to a number of aromatic substrates with significantly different steric and electronic properties. The iodination is generally highly regioselective and provides high yields of isolated products. NMR kinetic investigations conducted in THF-d 8indicate the role of sulfur in the thiourea motif as a nucleophile that is assisted by H-bonding in the key steps of the reaction. Georg Thieme Verlag Stuttgart . New York.
- Jakab, Gergely,Hosseini, Abolfazl,Hausmann, Heike,Schreiner, Peter R.
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supporting information
p. 1635 - 1640
(2013/07/27)
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- Ortho vs ipso: Site-selective pd and norbornene-catalyzed arene c-h amination using aryl halides
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A Pd and norbornene-catalyzed ortho-arene amination via Catellani-type C-H functionalization is reported. Aryl halides are used as substrates; N-benzoyloxyamines and isopropanol are employed as the amine source (oxidant) and reductant respectively. Exampl
- Dong, Zhe,Dong, Guangbin
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supporting information
p. 18350 - 18353
(2014/01/06)
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- Mild arming and derivatization of natural products via an In(OTf) 3-catalyzed arene iodination
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Figure presented Iodination of arene-containing natural products employing N-iodosuccinimide catalyzed by In(OTf)3 at ambient temperature is reported as a versatile and mild method for natural product derivatization amenable to small scale. This process facilitates natural product derivatization of arene moieties for SAR studies, homo- and heterodimerization of natural products, and also conjugation with reporters such as biotin via subsequent metal-mediated coupling reactions.
- Zhou, Cong-Ying,Li, Jing,Peddibhotla, Satyamaheshwar,Romo, Daniel
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supporting information; experimental part
p. 2104 - 2107
(2010/09/15)
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- The synthesis and SAR of 2-arylsulfanylphenyl-1-oxyalkylamino acids as GlyT-1 inhibitors
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Elevation of glycine levels by inhibition of the glycine transporter-1 (GlyT-1) and activation of the NMDA receptor is a potential strategy for the treatment of schizophrenia. A novel series of 2-arylsulfanylphenyl-1-oxyalkyl amino acids have been identif
- Smith, Garrick,Mikkelsen, Gitte,Eskildsen, Jorgen,Bundgaard, Christoffer
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p. 3981 - 3984
(2007/10/03)
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- HETEROCYCLIC KINASE INHIBITORS
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Compounds having the formula (I) are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.
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- Cation Radicals as Intermediates in Aromatic Halogenation with Iodine Monochloride: Solvent and Salt Effects on the Competition between Chlorination and Iodination
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Three distinct classes of substitutional reactivity can be discerned in the halogenation of a series of methyl-substituted methoxybenzenes (ArH) with iodine monochloride (ICl), namely, exclusive iodination, exclusive chlorination, and mixed iodination/chlorination.Spectral studies establish the prior formation of the charge-transfer complex which suffers electron transfer to afford the reactive triad .+,I.,Cl(-)> according to Scheme 1.Separate reactivity studies show that chlorination and iodination can result from the quenching of the aromatic cation radical by chloride and iodine (atom), respectively.Iodination versus chlorination thus represents the competition between radical-pair and ion-pair collapse from the reactive triad, and it is predictably modulated by solvent polarity and added salt.
- Hubig, S. M.,Jung, W.,Kochi, J. K.
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p. 6233 - 6244
(2007/10/02)
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