- Synthesis of 14C-labeled 4-hydroxyindole as an intermediate for the preparation of (S)-2-14-12-13-(indol-2-[14C]-4-yloxy)-2-hydroxypropylaminol -2-methylpropyl]- phenoxylpyridine-5-carboxamide (LY368842-[indole-14C]) glyco
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Synthesis of 4-hydroxyindole labeled with 14C at the 2-position was accomplished based on the vicarious nucleophilic substitution reaction of benzyl-protected 3-nitrophenol with p-chlorophenoxyacetonitrile-[1-14C]. This was followed
- Czeskis, Boris A.,Clodfelter, Dean K.,Wheeler, William J.
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Read Online
- Preparation method of M-aminophenol
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The invention discloses a preparation method of m-aminophenol. The preparation method comprises the following steps: 1, using m-dinitrobenzene and benzyl alcohol as raw materials, adding an organic solvent 1, inorganic alkali and a phase transfer catalyst, stirring and heating to 60-150 DEG C, reacting for 3-8 hours, and cooling and concentrating the reaction product to obtain an m-nitrobenzyl ether intermediate product; 2, putting the m-nitrobenzyl ether intermediate product into an organic solvent 2, under the action of a hydrogenation reduction catalyst, hydrogen, hydrazine hydrate or ammonium formate is used as a hydrogen source, a reduction reaction is carried out, after the reaction is completed, the hydrogenation reduction catalyst is filtered and recovered, filtrate is subjected toconcentration, alkali liquor treatment and toluene extraction separation to recover a solvent, a water phase is subjected to acid neutralization to separate out a product, and recrystallization, filtration and vacuum drying are carried out to obtain an m-aminophenol target product. The method is mild in reaction condition and high in yield; high-temperature operation in the production process isavoided; the catalyst and the solvent can be recycled; subsequent treatment environmental protection pressure is low.
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Paragraph 0023; 0025; 0027; 0029; 0031
(2020/12/14)
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- A inter-b-aminophenol preparation method
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The invention belongs to organic synthesis and chemical raw material preparation technical field, and in particular relates to inter-b-aminophenol and intermediate preparation method, inter-b-aminophenol of the preparation method, comprises the steps of: (1) dinitrobenzene substituted benzyl alcohol generated by the reaction with 1 - benzyloxy - 3 - nitrophenyl; (2) 1 - benzyloxy - 3 - nitrobenzene with acetaldehyde in the foaming PH to acid substituted in the reaction solution, or 1 - benzyloxy - 3 - nitrobenzene with acetaldehyde to replace after the recovery of the solvent of the reaction solution dissolved in the dissolving of the re-dissolved solution in organic solvent, by reducing amination and catalytic debenzylation of hydrogenation generating inter-b-aminophenol. 1 - Benzyloxy - 3 - nitrophenyl without separation and purification, directly with the aldehyde and hydrogen reduction amination and debenzylation of hydrogenation reaction. The method is simple, mild condition, equipment strength requirement is low, not produce waste, environment friendly, easily available raw materials, high yield, is suitable for the large-scale generation.
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Paragraph 0052-0054
(2019/07/01)
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- A preparation method of the m-aminophenol
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The invention belongs to organic synthesis and chemical raw material preparation technology field, in particular to m-aminophenol of preparation method and its intermediate, m-aminophenol of the preparation method, comprises the steps of: (1) dinitrobenzene substituted with benzyl alcohol produced by the reaction of 1 - benzyloxy - 3 - nitrophenyl; (2) 1 - benzyloxy - 3 - nitrobenzene for filtering of the alkaline inorganic salt the substitution reaction of the liquid catalytic hydrogenation generating m-aminophenol; or, 1 - benzyloxy - 3 - nitrophenyl replace alkaline inorganic salt and filtered out of the reaction solution after the recovery of the solvent is soluble in the organic solvent and then re-dissolved in the solution of the, generated by the catalytic hydrogenation of m-aminophenol. Without intermediate separation and purification processes, direct catalytic hydrogenation "one-pot" process for preparing m-aminophenol; then the re-crystallization or reduced pressure distillation purification of m-aminophenol. The method is simple, mild reaction conditions, equipment strength requirement is low, not generate intermediate waste, environment-friendly, high yield, is suitable for industrial generation.
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Paragraph 0014; 0038-0041
(2019/07/08)
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- [Cp?RhCl2]2-catalyzed alkyne hydroamination to 1,2-dihydroquinolines
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[Cp?RhCl2]2 catalyzes the formation of 1,2-dihydroquinolines from the reaction of two terminal alkynes and an aniline. This reaction is believed to proceed via an alkyne hydroamination followed by an alkyne insertion.
- Kumaran, Elumalai,Leong, Weng Kee
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p. 1779 - 1782
(2015/05/20)
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- Copper MOF: Scope and limitation in catalytic hydroxylation and nitration of aryl halides
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The potential catalytic application of MOFs like [Cu3(btc) 2] (btc=1,3,5-benzenetricarboxylate), [Cu(bdc)] (bdc=1,4- benzenedicarboxylate), [Cu(pymo)2] (pymo=2-hydroxypyrimidinalote) and [Cu(im)2] (im=imidazolate) was explored in the hydroxylation and nitration of aryl halides. Cu3(btc)2 was found to be superior for both the reactions furnishing good to excellent yields of the respective products. The studies demonstrated that MOFs are not recyclable, attributable to their instability in the highly polar and basic conditions demanded for these reactions. Complete transformation of MOFs to copper oxide nanoparticles occurred in hydroxylation, whereas significant alteration in frameworks was observed for the recovered catalyst in nitration.
- Priyadarshini,Amal Joseph,Kantam, M. Lakshmi,Sreedhar
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p. 6409 - 6414
(2013/07/26)
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- Synthesis and biological evaluation of direct thrombin inhibitors bearing 4-(piperidin-1-yl)pyridine at the P1 position with potent anticoagulant activity
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The design and synthesis of a new class of nonpeptide direct thrombin inhibitors, built on the structure of 1-(pyridin-4-yl)piperidine-4-carboxamide, are described. Starting from a strongly basic 1-amidinopiperidine derivative (6) showing poor thrombin (fIIa) and factor Xa (fXa) inhibition activities, anti-fIIa activity and artificial membrane permeability were considerably improved by optimizing the basic P1 and the X-substituted phenyl P4 binding moieties. Structure-activity relationship studies, usefully complemented with molecular modeling results, led us to identify compound 13b, which showed excellent fIIa inhibition (Ki = 6 nM), weak anti-Xa activity (K i = 5.64 μM), and remarkable selectivity over other serine proteases (e.g., trypsin). Compound 13b showed in vitro anticoagulant activity in the low micromolar range and significant membrane permeability. In mice (ex vivo), 13b demonstrated anticoagulant effects at 2 h after oral dosing (100 mg·kg-1), with a significant 43% prolongation of the activated partial thromboplastin time (aPTT), over controls (P 0.05).
- De Candia, Modesto,Fiorella, Filomena,Lopopolo, Gianfranco,Carotti, Andrea,Romano, Maria Rosaria,Lograno, Marcello Diego,Martel, Sophie,Carrupt, Pierre-Alain,Belviso, Benny D.,Caliandro, Rocco,Altomare, Cosimo
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p. 8696 - 8711
(2013/12/04)
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- Synthesis of novel 5-substituted isoxazole-3-carboxamide derivatives and cytotoxicity studies on lung cancer cell line
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A series of novel 5-substituted isoxazole-3-carboxamide derivatives 6 have been prepared by coupling of 5-substituted isoxazole-3-carboxylic acids 3 with substituted-3-benzyloxyaniline 5 using DCC/HOBT as coupling agent. The products 6 have been evaluated for cytotoxicity on A549 lung cancer cell line and compounds 6a, 6b, 6e, 6j are found to show moderate proliferative activity and low cytotoxicity.
- Veeraswamy,Kurumurthy,Santhosh Kumar,Sambasiva Rao,Thelakkat, Kavya,Kotamraju, Srigiridhar,Narsaiah
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p. 1369 - 1375
(2012/11/13)
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- Copper catalyzed ipso-nitration of iodoarenes, bromoarenes and heterocyclic haloarenes under ligand-free conditions
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A catalytic protocol for the conversion of haloarenes into the corresponding nitroarenes is presented using copper salts under ligand-free conditions. The method was effectively utilized for the ipso-nitration of a broad variety of haloarenes that includes iodoarenes, bromoarenes, and heterocyclic haloarenes.
- Amal Joseph,Priyadarshini,Lakshmi Kantam,Maheswaran
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supporting information; experimental part
p. 1511 - 1513
(2012/03/27)
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- Synthesis and adrenolytic activity of 1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol and its enantiomers. Part 1
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The synthesis of (2RS)-1-(1H-indol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol ((RS)-9) and its enantiomers has been described and tested for electrocardiographic, antiarrhythmic, hypotensive and spasmolytic activities as well as for α1-, α2- and β1-adrenoceptors' binding affinities. All compounds significantly decrease systolic and diastolic blood pressure, and possess antiarrhythmic activity and affinity to α1-, α2- and β1-adrenoceptors. The results suggest that the antiarrhythmic and hypotensive effects of these compounds are related to their adrenolytic but not spasmolytic properties.
- Groszek, Grazyna,Bednarski, Marek,Dybala, Malgorzata,Filipek, Barbara
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scheme or table
p. 809 - 817
(2009/09/05)
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- Fluorinated benzyloxyphenyl piperidine-4-carboxamides with dual function against thrombosis: Inhibitors of factor xa and platelet aggregation
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A series of benzyloxy anilides of nipecotic (5, 6) and isonipecotic (7, 8) acids were synthesized and assayed in vitro as inhibitors of ADP-induced platelet aggregation and the blood coagulation enzymes factor Xa (FXa) and thrombin (Flla). An exploration of effects of the amidine group attached at the piperidine nitrogen, position and substitution (F, phenyl) of the benzyloxy group, and addition of fluorine/s on the second (distal) phenyl ring, led us to single out some promising isonipecotamide derivatives 7. Addition of meta-F and para-CF3 on the distal phenyl ring resulted in a 6-to-18-fold enhancement of the FXa potency and in 2-to- 4-fold increase of the antiplatelet potency, the last depending to a large extent upon lipophilicity. Two congeners of N-{[3-(1,1′-biphenyl-4-yl)methoxy]phenyljpiperidine-4-carboxamide (7m and 7p) proved to be potent FXa-selective inhibitors (Ki = 130 and 57 nM, respectively) and antiplatelet agents and were identified as leads for developing new dual function antithrombotic drugs.
- De Candia, Modesto,Liantonio, Francesco,Carotti, Andrea,De Cristofaro, Raimondo,Altomare, Cosimo
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experimental part
p. 1018 - 1028
(2009/12/24)
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- Counterattack mode differential acetylative deprotection of phenylmethyl ethers: Applications to solid phase organic reactions
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A counterattack protocol for differential acetylative cleavage of phenylmethyl ether has been developed. The phenylmethyl moiety is liberated as benzyl bromide that is isolated and reused providing advantages in terms of waste minimization/utilization and atom economy. The applicability of this methodology has been extended for solid phase organic reactions with the feasibility of reuse of the solid support.
- Chakraborti, Asit K.,Chankeshwara, Sunay V.
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supporting information; experimental part
p. 1367 - 1370
(2009/07/04)
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- Design, synthesis, and anti-HCV activity of thiourea compounds
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A series of thiourea derivatives were synthesized and their antiviral activity was evaluated in a cell-based HCV subgenomic replicon assay. SAR studies revealed that the chain length and the position of the alkyl linker largely influenced the in vitro anti-HCV activity of this class of potent antiviral agents. Among this series of compounds synthesized, the thiourea derivative with a six-carbon alkyl linker at the meta-position of the central phenyl ring (10) was identified as the most potent anti-HCV inhibitor (EC50 = 0.047 μM) with a selectivity index of 596.
- Kang, Iou-Jiun,Wang, Li-Wen,Lee, Chung-Chi,Lee, Yen-Chun,Chao, Yu-Sheng,Hsu, Tsu-An,Chern, Jyh-Haur
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scheme or table
p. 1950 - 1955
(2009/11/30)
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- Aromatic 2-chloroethyl urea derivatives and bioisosteres. Part 2: Cytocidal activity and effects on the nuclear translocation of thioredoxin-1, and the cell cycle progression
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Recently, a subset of N-phenyl-N′-(2-chloroethyl)ureas (CEU) was found abrogating the nuclear translocation of thioredoxin-1 and arresting the cell cycle in G0/G1 phase. Several derivatives were prepared to assess their effect on cell cycle progression and on the intracellular location of Trx-1. Compounds 1-20, 21-40, and 41-60 exhibited GI50 between 1 and 80 μM. Immunocytochemistry analysis showed compounds 4, 6, 8, 10, 11, 23, 24, 26-31, 34, 37, 41, 44, 46-51, 53, 56, and 57 inhibiting the nuclear translocation of Trx-1. Our results suggest that increasing the electrophilic character of these molecules might enhance the antiproliferative activity at the expense of the selectivity toward thioredoxin-1 and the G0/G1 phase arrest.
- Fortin, Jessica S.,Cote, Marie-France,Lacroix, Jacques,Petitclerc, Eric,C.-Gaudreault, Rene
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p. 7477 - 7488
(2008/12/22)
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- SOLUBLE EPOXIDE HYDROLASE INHIBITORS
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Disclosed are urea and thiourea compounds and compositions that inhibit soluble epoxide hydrolase (sEH), methods for preparing the compounds and compositions, and methods for treating patients with such compounds and compositions. The compounds, compositions, and methods are useful for treating a variety of sEH mediated diseases, including hypertensive, cardiovascular, inflammatory, and diabetic-related diseases.
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Page/Page column 89
(2008/12/07)
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- Solvent-free Williamson synthesis: An efficient, simple, and convenient method for chemoselective etherification of phenols and bisphenols
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Etherification of phenols with dimethyl- and diethylsulfates and benzyl chloride was performed efficiently in the presence of a suitable solid base, NaHCO3 or K2CO3, under solvent-free conditions. The reaction proceeded rapidly at low temperature, and the corresponding ethers were obtained with high purity and excellent yield. Selective etherification of electron-poor phenols in the presence of electron-rich ones and also selective mono-etherification of bisphenols are the noteworthy advantages of this method. This method is environmentally friendly. Copyright Taylor & Francis Group, LLC.
- Massah, Ahmad R.,Mosharafian, Masumeh,Momeni, Ahamad R.,Aliyan, Hamid,Naghash, H. Javaherian,Adibnejad, Mohamad
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p. 1807 - 1815
(2008/02/02)
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- Oligomeric benzylsulfonium salts: Facile benzylation via high-load ROMP reagents
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(Chemical Equation Presented) The development of high-load, oligomeric benzylsulfonium salts, generated via ring-opening metathesis polymerization, and their utility in facile benzylations of various nucleophiles is reported. These oligomeric sulfonium salts exist as free-flowing powders and are stable at room temperature. After the benzylation event, purification is attained via simple dry load/filtration, followed by solvent removal to deliver products in excellent yield and purity.
- Zhang, Mianji,Flynn, Daniel L.,Hanson, Paul R.
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p. 3194 - 3198
(2008/02/04)
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- Fluorescent Dyes and Complexes
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A fluorescent dye comprising a xanthene-derived fluorophore having the formula (I) wherein R1, R2, R3, R4, R5 and R6 are independently selected from H, alkyl, alkoxy, alcohol, ether, alkenyl, alkenoxy, aryl, alkaryl, aralkyl and amido, except that R1, R4 and/or R5 is not H when bonded to Y, Y1 or Y2, respectively; X is either O? or S?; and at least one of Y, Y1, Y2, Y3, Y4 and Y5 is a group for covalently bonding the dye, optionally through. the use of a coupling agent, to a target molecule, and is otherwise H. The dye may be covalently attached to a target molecule to form a complex, and the dye and/or complex finds use in cell analysis techniques, particularly pH measurement and analysis of kinetics of migration.
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Page/Page column 8
(2008/06/13)
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- Surfactant-mediated solvent-free dealkylative cleavage of ethers and esters and trans-alkylation under neutral conditions
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A simple, surfactant-mediated, one-pot, solvent-free dealkylative cleavage of aryl ethers and esters followed by subsequent optional trans-alkylation under essentially neutral conditions has been developed.
- Bhattacharya, Apurba,Patel, Nitin C.,Vasques, Tomas,Tichkule, Ritesh,Parmar, Gaurang,Wu, Jiejun
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p. 565 - 567
(2007/10/03)
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- SUBSTITUTED ARYLTHIOUREA DERIVATIVES USEFUL AS INHIBITORS OF VIRAL REPLICATION
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Substituted arylthiourea compounds of Formula I, and the pharmaceutically acceptable salts of such compounds, useful as antiviral agents, are provided herein. Certain substituted arylthioureas disclosed herein are potent and/ or selective inhibitors of viral replication, particularly Hepatitis C virus replication. Pharmaceutical compositions containing one or more substituted arylthiourea compounds and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein. Such pharmaceutical compositions may contain a substituted arylthiourea as the only active agent or may contain a combination of a substituted arylthiourea derivative and one or more other pharmaceutically active agents. Methods of treating Hepatitis C viral infections in mammals are also provided herein.
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Page/Page column 35-36
(2010/02/10)
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- The α-Effect in Benzyl Transfers from Benzylphenylmethyl Sulfonium Salts to N-Methylbenzohydroxamate Anions
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The investigation of the occurrence of the α-effect in group transfers from phenyldialkyl sulfonium ions where one alkyl group is benzyl allows an assay of the effect of changing the nature of the C atom being transferred. The size of the α-effect responds to increasing electron demand, as methyl transfers do. Quantitative relationships between the size of the α-effect are established from both the nucleophilic side and the leaving group side of the SN2 transition state.
- Fountain,Tad-y, Darlene B.,Paul, Timothy W.,Golynskiy, Mikhail V.
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p. 6547 - 6553
(2007/10/03)
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- Nucleophilic Substitution of Nitrite in Nitrobenzenes, Nitrobiphenyls and Nitronaphthalenes
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Aromatic compounds, accessible only by multistep procedures, can be synthesized easily by nucleophilic substitution of nitrite in nitrobenzenes, nitrobiphenyls, and nitronaphthalines.Thus, meta-substituted phenols 3, 4, and 7 are obtained from 1,3-dinitrobenzene (1) and meta-substituted nitrobenzenes 6, as well as 3,5-disubstituted phenols 10 and 5-substituted resorcinol derivatives 11 from 3,5-disubstituted nitrobenzenes 9.The unsymmetrically substituted nitrobiphenyls 13, 15, 17, 19, 23, 24, and 26 are also available by nitrite exchange from the corresponding easily accessible dinitrobiphenyls 16, 18, 20, 22, and 25.A nitrite exchange with nucleophiles is easily possible in the 1,5-disubstituted naphthalenes 29, 34, while in the case of the 1,8-disubstituted naphthalenes 31, 36 only the chloro derivative 36 undergoes this exchange under much stronger conditions in low yield.
- Effenberger, Franz,Koch, Markus,Streicher, Willi
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p. 163 - 173
(2007/10/02)
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- Reactions of Organic Anions, 147.- Simple and General Synthesis of Hydroxy- and Methoxyindoles via Vicarious Nucleophilic Substitution of Hydrogen
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A simple synthesis of 4-, 5-, 6-, and 7-hydroxy- and -methoxyindoles via cyanoalkylation of O-protected nitrophenols by vicarious nucleophilic substitution of hydrogen, followed by catalytic hydrogenation of the (2-nitroaryl)acetonitriles obtained is described.
- Makosza, Mieczyslaw,Danikiewicz, Witold,Wojciechowski, Krzysztof
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p. 203 - 208
(2007/10/02)
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