- QUINAZOLINE DERIVATIVES AS TYROSINE KINASE INHIBITOR, COMPOSITIONS, METHODS OF MAKING THEM AND THEIR USE
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The present disclosure relates to new compounds or pharmaceutically acceptable salts or stereoisomers thereof of formula I as inhibitors of receptor tyrosine kinases (RTK), in particular extracellular mutants of ErbB-receptors. The present disclosure also relates to methods of preparation these compounds, compositions comprising these compounds, and methods of using them in the treatment of cancer in mammals (e.g. humans).
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Page/Page column 497
(2020/05/13)
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- Preparation method of 3-aminopropanol
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The invention relates to a preparation method of 3-aminopropanol, wherein the preparation method comprises the following steps: (1) carrying out a reaction on acrylonitrile with benzyl alcohol under the catalysis of a base catalyst, and separating the obtained reaction solution to obtain 3-benzyloxypropionitrile; and (2) in a liquid-phase reaction system in the presence of a hydrogenation catalyst, carrying out a hydrogenation reaction on the 3-benzyloxypropionitrile, separating the obtained reaction liquid to obtain 3-aminopropanol, and recycling the obtained by-product toluene as an extractant in the step (1).
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Paragraph 0040; 0041; 0043; 0044; 0046; 0047; 0049; 0050
(2020/05/05)
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- Formation of a New, Strongly Basic Nitrogen Anion by Metal Oxide Modification
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Development of new hybrid materials having unique and unprecedented catalytic properties is a challenge for chemists, and heterogeneous-homogeneous hybrid catalysts have attracted much attention because of the preferable and exceptional properties that are highly expected to result from combination of the components. Base catalysts are widely used in organic synthesis as key materials, and a new class of base catalysts has made a large impact from academic and industrial viewpoints. Here, a principle for creating a new strong base by hybridization of homogeneous and heterogeneous components is presented. It is based on the modification of organic compounds with metal oxides by using the acid-base property of metal oxides. Based on kinetic and DFT studies, combination of CeO2 and 2-cyanopyridine drastically enhanced the basicity of 2-cyanopyridine by a factor of about 109 (~9 by pKa (in CH3CN)), and the pKa was estimated to be ~21, which locates it in the superbase category. 2-Cyanopyridine and CeO2 formed a unique adsorption complex via two interaction modes: (i) coordinative interaction between the Ce atom of CeO2 and the N atom of the pyridine ring in 2-cyanopyridine, and (ii) covalent interaction between the surface O atom of CeO2 and the C atom of the CN group in 2-cyanopyridine by addition of the lattice oxygen of CeO2 to the CN group of 2-cyanopyridine. These interactions established a new, strongly basic site of N- over the CeO2 surface.
- Tamura, Masazumi,Kishi, Ryota,Nakayama, Akira,Nakagawa, Yoshinao,Hasegawa, Jun-Ya,Tomishige, Keiichi
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p. 11857 - 11867
(2017/09/08)
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- PARTIALLY SATURATED NITROGEN-CONTAINING HETEROCYCLIC COMPOUND
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There are provided compounds having a superior PHD2 inhibitory effect that are represented by general formula (I'): (in the above-mentioned general formula (I'), W, Y, R2, R3, R4, and Y4 are as described hereinabove), or pharmaceutically acceptable salts thereof.
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Paragraph 0279; 0280
(2015/06/17)
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- Organocatalytic conjugate addition of cyclopropylacetaldehyde derivatives to nitro olefins: En route to β- and γ-amino acids
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Cyclopropane-containing amino acids are important pharmaceuticals and biologically active compounds. A new organocatalytic asymmetric Michael reaction has been developed. This allows the one-step introduction of the cyclopropane ring, as well as two different nitrogen-containing functional groups (tert-butoxycarbonylamino and nitro) into the target compounds. All the products were isolated in good yields with moderate to excellent enantio- and diastereoselectivities.
- Kaasik, Mikk,Noole, Artur,Reitel, K?rt,J?rving, Ivar,Kanger, T?nis
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p. 1745 - 1753
(2015/05/27)
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- Chemoselective catalytic conjugate addition of alcohols over amines
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A highly chemoselective conjugate addition of alcohols in the presence of amines is described. The cooperative nature of the catalyst enabled chemoselective activation of alcohols over amines, allowing the conjugate addition to soft Lewis basic α,β-unsaturated nitriles. Divergent transformation of the nitrile functionality highlights the utility of the present catalysis. The cooperative nature of a copper catalyst enabled the highly chemoselective activation of alcohols in the presence of amines and thus the conjugate addition of the hydroxy group to soft Lewis basic α,β-unsaturated nitriles. The presented method proceeds under proton-transfer conditions, reverses the innate reactivity of the OH and NH groups, and does not require protecting groups. dppe=1,2-bis(diphenylphosphino) ethane, MeSal=3-methylsalicylate. Copyright
- Uesugi, Shuhei,Li, Zhao,Yazaki, Ryo,Ohshima, Takashi
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supporting information
p. 1611 - 1615
(2014/03/21)
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- Benzylation of hydroxy groups with tertiary amine as a base
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The benzylation of hydroxy groups in the presence of tertiary amines is described. A mixture of an alcohol and a benzyl halide afforded the corresponding benzyl ether in good to excellent yields in the presence of diisopropylethylamine. The importance of solventless conditions was observed. The reaction showed high tolerance to many functional groups including benzoate, even at a reaction temperature of 150 °C. Sodium iodide was found to be an efficient catalyst to accelerate the reaction.
- Gathirwa, Jeremiah W.,Maki, Toshihide
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experimental part
p. 370 - 375
(2012/01/14)
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- Hydroamination and alcoholysis of acrylonitrile promoted by the pincer complex {κP,κC,κP-2,6- (Ph2PO)2C6H3}Ni(OSO 2CF3)
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This report describes the catalytic activity of the pincer-type complex {κP,κC,κP-2,6-(Ph 2PO)2C6H3}Ni(OSO2CF 3) (1) in the anti-Markovnikov addition of aliphatic and aromatic amines and alcohols to acrylonitrile, crotonitrile, and methacrylonitrile. The influence of additives on the catalytic activities was investigated, and it was found that substoichiometric quantities of water promoted the C-N bond forming reactions catalyzed by 1, especially the reactions involving aromatic amines; in comparison, NEt3 had a less dramatic impact. The opposite pattern was observed for the alcoholysis of acrylonitrile promoted by 1: water had no beneficial effect on these reactions, while NEt3 proved to be a potent promoter. Another important difference between these reactions is that hydroamination works better with more nucleophilic amines, whereas the alcoholysis reactions work well with ArOH, CF3CH2OH, and ArCH2OH but not at all with the more nucleophilic aliphatic alcohols methanol, ethanol, and 2-propanol. Both hydroamination and alcoholysis proceed much better with acrylonitrile in comparison to its Me-substituted derivatives crotonitrile and methacrylonitrile. Under optimized conditions, precatalyst 1 promotes conjugate additions to acrylonitrile with catalytic turnover numbers of up to 100 (hydroamination) or higher (alcoholysis). Spectroscopic studies have established that the main Ni-containing species in the hydroamination reactions is a cationic adduct in which the olefinic substrate is bound to the Ni center via its nitrile moiety; this binding activates the double bond toward an outer-sphere nucleophilic attack by the amine (Michael addition). The solid-state structures of the cationic nitrile adducts [{κP, κC,κP-2,6-(Ph2PO)2C 6H3}Ni(NCR)][OSO2CF3] (R = Me (2a), CH2CH2N(H)Ph (2e)), which can be regarded as model complexes for the species involved in the hydroamination catalysis, have been elucidated. Also reported are the solid-state structures of the charge-neutral compound {κP,κC,κP-2,6-(i- Pr2PO)2C6H3}Ni(OSO 2CF3) and an octahedral Ni(II) species resulting from the aerobic/hydrolytic oxidation of 1.
- Salah, Abderrahmen B.,Offenstein, Caroline,Zargarian, Davit
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experimental part
p. 5352 - 5364
(2011/12/13)
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- Solid sodium stannate as a high-efficiency superbase catalyst for anti-Markovnikov hydroamination and hydroalkoxylation of electron-deficient olefins under mild conditions
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A solid superbase with H- above 26.5 has been obtained through thermal treatment of sodium stannate hydrate. It was found to be an efficient catalyst for anti-Markovnikov hydroamination and hydroalkoxylation of electron-deficient olefins under mild conditions.
- Zhang, Shuguo,Wei, Yudan,Yin, Shuangfeng,Au, Chak-Tong
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p. 712 - 716
(2013/01/09)
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- Monomeric and dimeric nickel complexes derived from a pincer ligand featuring a secondary amine donor moiety
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Reaction of NiBr2(CH3CN)x with the unsymmetrical pincer ligand m-(i-Pr2PO)(CH2NHBn)C 6H4 (Bn = CH2Ph) gives the complex (R,S)-κP,κC,κN-{2-(i-Pr 2PO),6-(CH2NHBn)-C6H3}Ni IIBr, 1, featuring an asymmetric secondary amine donor moiety. Deprotonation of the latter with methyl lithium gave a dark brown compound that could not be characterized directly, but fully characterized derivatives prepared from this compound indicate that it is the LiBr adduct of the 14-electron amido species [κP,κC, κN-{2-(i-Pr2PO),6-(CH2NBn)-C 6H3}Ni], 2. Thus, 2·LiBr reacts with water to regenerate 1, while reaction with excess benzyl or allyl bromide gave the POCN-type pincer complexes 3 and 4, respectively, featuring tertiary amine donor moieties. On the other hand, heating 2·LiBr at 60 °C led to loss of LiBr and dimerization to generate the orange crystalline compound [μN;κP,κC,κN- {2-(i-Pr2PO),6-(CH2NBn)-C6H3}Ni] 2, 5. Solid state structural studies show that 1, 3, and 4 are monomeric, square planar complexes involving one Ni?N interaction, whereas complex 5 is a C2-symmetric dimer involving four Ni?N interactions and a Ni2N2 core featuring a short Ni?Ni distance (2.51 A). Preliminary reactivity tests have shown that 5 is stable toward weak nucleophiles such as acetonitrile but reacts with strong nucleophiles such as CO or 2,6-Me2(C6H3)NC. Reactions with protic reagents showed that phthalimide appears to break the dimer to generate a monomeric species, whereas alcohols appear to leave the dimer intact, giving rise instead to adducts through N...H...O interactions. These ROH adducts of 5 were found to be active precatalysts for the alchoholysis of acrylonitrile with up to 2000 catalytic turnover numbers.
- Spasyuk, Denis M.,Zargarian, Davit
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experimental part
p. 6203 - 6213
(2010/08/21)
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- Gold-catalyzed substitution reaction with ortho-alkynylbenzoic acid alkyl ester as an efficient alkylating agent
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ortho-Alkynylbenzoic acid alkyl esters behave as alkylating agents in combination with gold catalysts. The reaction with alcohols occurs smoothly in the presence of catalytic amounts of Ph3PAuCl and AgOTf under mild conditions to produce the corresponding ether products in high yields. The protocol is also useful for Friedel-Crafts alkylation and N-alkylation of sulfonamides. The reaction likely proceeds through the gold-induced in situ construction of leaving groups and subsequent nucleophilic attack of nucleophiles, such as alcohols, aromatic compounds, and sulfonamides.
- Aikawa, Haruo,Tago, Sakie,Umetsu, Kazuteru,Haginiwa, Naomichi,Asao, Naoki
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experimental part
p. 1774 - 1784
(2009/06/20)
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- Formal total synthesis of neopeltolide
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A concise synthesis of the core structure of the macrolide neopeltolide was develop featuring a Prins cyclization to fashion the pyran ring. Key steps in the synthesis of aldehyde 16 were a Leiqhton allylation and a Feringa-Minnaard asymmetric methyl cuprate addition to an unsaturated thioester. For lactonization, a classical Yamaguchin macrolactonization was used. The longest linear sequence consists of 17 steps providing lactone 26 with an overall yield of 23%.
- Vintonyak, Viktor V.,Maier, Martin E.
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body text
p. 1239 - 1242
(2009/04/12)
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- Gold-catalyzed etherification and friedel - Crafts alkylation using ortho-alkynylbenzoic acid alkyl ester as an efficient alkylating agent
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A gold-catalyzed alkylation of alcohols and aromatic compounds is described. The reaction of ortho-alkynylbenzoic acid alkyl esters with alcohols or aromatic compounds occurs in the presence of catalytic amounts of Ph 3PAuCl and AgOTf under mild conditions to produce corresponding ethers or Friedel-Crafts alkylation products in good to high yields. The reaction likely proceeds through the gold-induced in situ construction of leaving groups and subsequent nucleophilic attack of alcohols or aromatic compounds.
- Asao, Naoki,Aikawa, Haruo,Tago, Sakie,Umetsu, Kazuteru
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p. 4299 - 4302
(2008/02/12)
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- FUNGICIDAL HETEROCYCLIC COMPOUNDS
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A compound which can specifically or selectively expresses an antifungal activity with a broad spectrum, based on the functional mechanism of 1,6-β-glucan synthesis inhibition, is provided, and an antifungal agent which comprises such a compound, a salt thereof or a solvate thereof is provided. A compound represented by the following formula (I), a salt thereof or a solvate thereof.
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Page/Page column 60
(2010/11/24)
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- Synthesis of Poly(propyl ether imine) Dendrimers and Evaluation of Their Cytotoxic Properties
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In this paper, we report the synthesis of several poly(propyl ether imine) dendrons and dendrimers. These dendrons and dendrimers were constructed by involving an ether as the linker component and an imine as the branching component. The divergent syntheses of dendrons and dendrimers were established with the aid of two alternate Michael addition reactions and two alternate reduction reactions in a four-step iterative synthetic sequence. Dendrons up to three generations were synthesized and some of the dendrons were attached to a benzenoid core so as to obtain dendrimers up to two generations containing 12 carboxylic acids at the periphery. Divergent synthesis involving ether as the core was found to be more facile, and dendrimers up to three generations having 16 carboxylic acids at the periphery were achieved in good to excellent yields in each individual step. The adopted synthetic sequence allows us to install either alcohol, an amine, or a carboxylic acid at their peripheries. The carboxylic acid-terminated dendrons and dendrimers were evaluated as to their cytotoxic properties, and while most dendrons and dendrimers did not exhibit any measurable cytotoxicity, even up to 100/μg/mL, the second-generation dendrimer with the benzenoid core exhibited a mild toxicity at concentrations above 30/μg/mL.
- Krishna, Thatavarathy Rama,Jayaraman, Narayanaswamy
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p. 9694 - 9704
(2007/10/03)
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- Synthesis and evaluation of a novel bleomycin A2 analogue: Continuing assessment of the linker domain
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The synthesis and evaluation of a bithiazole ester analogue of deglycobleomycin A2 that addresses the importance of the bithiazole-L-threonine amide for efficient DNA cleavage is described. (C) 2000 Elsevier Science Ltd.
- Boger,Aquila,Tse,Searcey
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p. 9493 - 9498
(2007/10/03)
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- PREPARATION OF β-HYDROXYPROPIONYL-GLUTAMATE AND β-HYDROXYPROPIONYL-ORNITHINE FOR STUDIES ON CLAVULANIC ACID BIOSYNTHESIS
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The synthesis of β-hydroxypropionyl-glutamate and of β-hydroxypropionyl-ornithine "dipeptides" in L- and DL-configuration required for studies on the biosynthesis of clavulanic acid is described.
- Gutman, Arie L.,Meyer, Elazar,Boltanski, Aviv
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p. 1311 - 1322
(2007/10/02)
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