- S -indole benzamide derivative as well as preparation method and application thereof
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S - Indole benzamide derivatives as well as a preparation method and application thereof relate to the technical field of pharmacy. The derivative has a structural formula. The specific preparation method comprises the following steps: taking indole as a starting raw material and performing acylation reaction. Reaction, oxidation reaction, (R)- (+) -tert-butylsulfenamide asymmetric synthesis reaction, hydrolysis reaction and acylation reaction to give the target product. By means of the method, a novel antiviral drug with a development prospect can be obtained, and the yield is high.
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Paragraph 0030; 0034-0036
(2021/09/15)
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- SUBSTITUTED TETRAHYDROPYRANOINDOLES, DERIVATIVES THEREOF, AND THEIR METHODS OF SYNTHESIS AND USE
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Disclosed herein are tetrahydropyranoindole compounds and derivatives thereof, as well as their methods of synthesis and use. The disclosed compounds may be synthesized by methods that utilize a cooperative hydrogen bond donor/Br?nsted acid system. The disclosed compounds may be useful for treating a disease, disorder, or a symptom thereof in a subject in need thereof, such as pain, swelling, and joint stiffness. The disclosed compounds also may be useful for treating cell proliferative diseases and disorders such as cancer.
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Paragraph 0152; 0153; 0197
(2021/01/25)
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- AZEPINO-INDOLES AND OTHER HETEROCYCLES FOR TREATING BRAIN DISORDERS
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The present invention provides azepino-indoles and other heterocycles and methods of using the compounds for treating brain disorders.
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Paragraph 0203
(2020/09/12)
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- Improved and Flexible Synthetic Access to the Spiroindole Backbone of Cebranopadol
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By changing the dimethylamino to a nitro group, a novel synthetic access to the spirocyclic opioid analgesic cebranopadol was developed that is much more efficient compared with the established route. On the basis of the α-acidity of α-nitrotoluene, the two-fold Michael addition to acrylate gave an acyclic precursor compound, which was easily transformed by Dieckmann condensation and decarboxylation to the cyclohexanone derivative needed for the annulation of the indole ring by an oxa-Pictet-Spengler reaction. As an additional benefit, the reduction of the nitro group furnished an amine, which could be late-stage-diversified to carboxamides, sulfonamides, ureas, and N-alkyl congeners. The transformation of the nitro group at the spirocyclic scaffold to the dimethylamino function of the actual title compound was achieved in one step with zinc/formic acid/formaldehyde in 83% yield.
- Christoffers, Jens,Schmidtmann, Marc,Wachtendorf, Daniel
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supporting information
p. 6420 - 6423
(2020/09/02)
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- Synthesis of chiral [2,3]-fused indolines through enantioselective dearomatization inverse-electron-demand Diels-Alder reaction/oxidation of indoles with 2-(2-nitrovinyl)-1,4-benzoquinone
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Enantioselective dearomatization inverse-electron-demand Diels-Alder reaction/oxidation of indoles with 2-(2-nitrovinyl)-1,4-benzoquinone was realised using a chiral bisoxazoline/zinc complex as a catalyst. This transformation allowed for the synthesis of enantioenriched six-membered [2,3]-fused indolines (up to 99% yield and 88% ee).
- Cheng, Shaobing,Liu, Hui,Liu, Min,Yuan, Weicheng,Zhang, Jiayan,Zhang, Xiaomei,Zhao, Sihan
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supporting information
p. 4200 - 4203
(2020/04/22)
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- Tandem Olefin Isomerization/Cyclization Catalyzed by Complex Nickel Hydride and Br?nsted Acid
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We disclose a nickel/Br?nsted acid-catalyzed tandem process consisting of double bond isomerization of allyl ethers and amines and subsequent intramolecular reaction with nucleophiles. The process is accomplished by [(Me3P)4NiH]N(SO2CF3)2 in the presence of triflic acid. The methodology provides rapid access to tetrahydropyran-fused indoles and other oxacyclic scaffolds under very low catalyst loadings.
- Kathe, Prasad M.,Caciuleanu, Alexandru,Berkefeld, Andreas,Fleischer, Ivana
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p. 15183 - 15196
(2020/11/30)
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- Aerobic Dehydrogenation of N-Heterocycles with Grubbs Catalyst: Its Application to Assisted-Tandem Catalysis to Construct N-Containing Fused Heteroarenes
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An aerobic dehydrogenation of nitrogen-containing heterocycles catalyzed by Grubbs catalyst is developed. The reaction is applicable to various nitrogen-containing heterocycles. The exceptionally high functional group compatibility of this method was confirmed by the oxidation of an unprotected dihydroindolactam V to indolactam V. Furthermore, by taking advantage of the oxygen-mediated structural change of the Grubbs catalyst, we integrated ring-closing metathesis and subsequent aerobic dehydrogenation to develop the novel assisted-tandem catalysis using molecular oxygen as a chemical trigger. The utility of the assisted-tandem catalysis was demonstrated by the concise synthesis of N-containing fused heteroarenes including a natural antibiotic, pyocyanine.
- Kawauchi, Daichi,Noda, Kenta,Komatsu, Yoshiyuki,Yoshida, Kei,Ueda, Hirofumi,Tokuyama, Hidetoshi
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supporting information
p. 15793 - 15798
(2020/10/12)
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- Design, synthesis and evaluation of novel (S)-tryptamine derivatives containing an allyl group and an aryl sulfonamide unit as anticancer agents
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A series of (S)-tryptamine derivatives containing an allyl group and an aryl sulfonamide unit were designed, synthesized and evaluated for their potential application as anticancer agents. The structures of the synthesized compounds were characterized by 1H NMR, 13C NMR and ESI-MS spectral analyses. The target compounds were evaluated for their in vitro cytotoxicity against HepG2, HeLa, CNE1 and A549 human cancer cell lines. Some of the synthesized compounds showed moderate to good anticancer activities against four selected cancer cell lines, among of which 6ag was found to be the most active analogue possessing IC50 values 16.5–18.7 μM. Further mechanism studies revealed that compound 6ag could significantly induce HepG2 cell cycle arrest at G1 phase, promote cell apoptosis, and inhibit the colony formation as well.
- Guo, Zhenbo,Xu, Yiming,Peng, Yujie,Haroon ur Rashid,Quan, Wei,Xie, Peng,Wu, Lichuan,Jiang, Jun,Wang, Lisheng,Liu, Xu
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supporting information
p. 1133 - 1137
(2019/03/06)
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- A is by aromatic carboxylic acid non-catalytic reaction of alcohol compound (by machine translation)
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The present invention discloses a non-catalytic reaction of the aromatic carboxylic acid preparation of alcohol compound. In an inert gas atmosphere, after dehydration and deoxidation treatment of the reaction bottle [...] borane and carboxylic acid stirring and mixing, reaction 6 - 12 hours to obtain borate, further hydrolyzed into alcohol; said carboxylic acid is benzoic acid, 4 - bromobenzoic acid, 4 - fluoro benzoic acid, 1 - naphthoic acid, 2 - methoxybenzene formic acid and the like. The invention for the first time in the absence of catalyst under the conditions of high-efficiently using carboxylic acid with borane generating borohydrite reaction, carbonyl compound with borane generating borohydrite reaction preparation borate, further hydrolysis alcohol, provides new programme. (by machine translation)
- -
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Paragraph 0030
(2019/04/17)
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- Iron-Catalyzed β-Alkylation of Alcohols
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β-Branched alkylated alcohols have been prepared in good yields using a double-hydrogen autotransfer strategy in the presence of our diaminocyclopentadienone iron tricarbonyl complex Fe1. The alkylation of some 2-arylethanol derivatives was successfully addressed with benzylic alcohols and methanol as alkylating reagents under mild conditions. Deuterium labeling experiments suggested that both alcohols (2-arylethanol and either methanol or benzyl alcohol) served as hydrogen donors in this cascade process.
- Bettoni, Leó,Gaillard, Sylvain,Renaud, Jean-Luc
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supporting information
p. 8404 - 8408
(2019/10/16)
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- Method for preparing alcoholic compound from anilino lithium compound as catalyst
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The invention relates to an application of an anilino lithium compound, in particular to a method for preparing an alcoholic compound from the anilino lithium compound as a catalyst. The catalyst, borane and carboxylic acid are stirred and mixed uniformly, subjected to a reaction and exposed to air to terminate the reaction, a reacted liquid is subjected to reduced-pressure treatment for solvent removal, silica gel and methanol are added, and the alcoholic compound is obtained by hydrolysis. The anilino lithium compound can perform high-activity catalysis on the reaction between carboxylic acid and borane at room temperature, dose of the catalyst is only 0.8mol% of the mole ratio of carboxylic acid, compared with the conventional catalysis system, the commercial reagent anilino lithium compound is used, reaction conditions are mild, and yield of borate with different substituents under limit conditions can reach 90% or higher.
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-
-
- Based on n-butyl aromatic carboxylic acid preparation of alcohol compound
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The present invention relates to n-butyl application, in particular to based on n-butyl aromatic carboxylic acid preparation of alcohol compound, the catalyst sequentially, borane and carboxylic acid uniformly stirred and mixed, exposed to the air after the reaction terminated in the reaction, the reaction solution under reduced pressure to remove the solvent, then adding silica gel methanol hydrolyzed to obtain the alcohol compound. The invention discloses a butyl lithium can be high activity under the room temperature condition of catalytic carboxylic acid and borane borohydride reaction, the catalyst levels are only the molar amount of carboxylic acid 0.5 μM %, compared with the prior catalytic system, using the commercial reagent is BuLi, mild reaction conditions, in under a limited condition of different substituents of the yield of the ester can reach 90% or more.
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-
- Method used for reduction of tertiary amide into alcohols and/or amines
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The invention discloses a method used for reduction of tertiary amide into alcohols and/or amines. The method comprises following steps: tertiary amide, an alkali metal reagent, and a proton donor agent are added into an organic solvent for a following reaction selectively: when the proton donor agent is a raw material alcohol and/or inorganic salt aqueous solution, the reaction product is an alcohol compound and/or tertiary amine compound. The method is capable of realizing selective reduction of tertiary amide into alcohols and tertiary amine compounds, the yield is high, the suitable rangeis wide, operation is safe and simple, the adopted raw materials are cheap and easily available; no precious metal catalyst, toxic silanes, and flammable and combustible metal hydrides are adopted; notoxic by product is generated; reaction is more friendly to the environment; problems in the prior art that amide compound reducing method operation is complex, conditions are strict, and control ofproducts is difficult are solved.
- -
-
Paragraph 0231-0234
(2019/08/07)
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- Br?nsted acid Catalysed Synthesis of 3-(2-Alkoxyethyl)indoles from α-Arylaminocyclobutanones and Alcohols
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A new Br?nsted acid catalysed solvent-free cascade reaction consisting of a ring closure-ring fission process between α-arylaminocyclobutanones and alcohols has been established, providing highly functionalised 3-(2-alkoxyethyl)indoles in good to excellent yields. (Figure presented.).
- Serusi, Lorenzo,Bonnans, Marie,Luridiana, Alberto,Secci, Francesco,Caboni, Pierluigi,Boddaert, Thomas,Aitken, David J.,Frongia, Angelo
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supporting information
p. 1908 - 1912
(2019/03/13)
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- A convenient synthesis of indole and 1,4-dihydropyridine hybrid macromolecules by dimerization of [2-(1h-indol-3-yl)ethyl]pyridinium salts
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The design and synthesis of a novel type of macrocyclic compounds containing indole and 1,4-dihydropyridine heterocyclic subunits is presented. The key reaction involved in the synthesis was a base-mediated dimerization of [2-(1H-indol-3-yl)ethyl]pyridinium salts. The structure of the macrocycles was unambiguously confirmed by NMR and HRMS spectroscopic and X-ray single crystal diffraction.
- Ling, Gang,Zhang, Jing,Zhang, Rong-Zheng,Han, Fu-She
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-
- Development of the Vinylogous Pictet–Spengler Cyclization and Total Synthesis of (±)-Lundurine A
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A novel vinylogous Pictet–Spengler cyclization has been developed for the generation of indole-annulated medium-sized rings. The method enables the synthesis of tetrahydroazocinoindoles with a fully substituted carbon center, a prevalent structural motif in many biologically active alkaloids. The strategy has been applied to the total synthesis of (±)-lundurine A.
- Nash, Aaron,Qi, Xiangbing,Maity, Pradip,Owens, Kyle,Tambar, Uttam K.
-
supporting information
p. 6888 - 6891
(2018/05/08)
-
- A Cooperative Hydrogen Bond Donor–Br?nsted Acid System for the Enantioselective Synthesis of Tetrahydropyrans
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Carbocations stabilized by adjacent oxygen atoms are useful reactive intermediates involved in fundamental chemical transformations. These oxocarbenium ions typically lack sufficient electron density to engage established chiral Br?nsted or Lewis acid catalysts, presenting a major challenge to their widespread application in asymmetric catalysis. Leading methods for selectivity operate primarily through electrostatic pairing between the oxocarbenium ion and a chiral counterion. A general approach to new enantioselective transformations of oxocarbenium ions requires novel strategies that address the weak binding capabilities of these intermediates. We demonstrate herein a novel cooperative catalysis system for selective reactions with oxocarbenium ions. This new strategy has been applied to a highly selective and rapid oxa-Pictet–Spengler reaction and highlights a powerful combination of an achiral hydrogen bond donor with a chiral Br?nsted acid.
- Maskeri, Mark A.,O'Connor, Matthew J.,Jaworski, Ashley A.,Davies, Anna V.,Scheidt, Karl A.
-
supporting information
p. 17225 - 17229
(2018/12/05)
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- Rapid One-Pot Access to Unique 3,4-Dihydrothiopyrano[3,4-b]indol-1(9H)-imines via Bi(OTf)3-Catalysed Tandem Friedel–Crafts Alkylation/Thia-Michael Addition
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A highly efficient and atom economical one-pot annulation strategy for novel tetrahydrothiopyrano[3,4-b]indoles is presented. This protocol involves a Bi(OTf)3 catalyzed tandem Friedel–Crafts alkylation and intramolecular thia-Michael addition reactions to furnish target molecules in an efficient manner. The method works effectively on substrates with unprotected indoles and also it is successfully employed to make tetrahydrothiepino[3,4-b]indoles. The scaffolds synthesized are diverse and first of the kind. The reaction is practically simple with broad substrate scope and vast functional group compatibility.
- Dethe, Dattatraya H.,Boda, Vijay Kumar,Mandal, Anupam
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supporting information
p. 5417 - 5421
(2018/10/20)
-
- Efficient Synthesis of the Peptide Fragment of the Natural Depsipeptides Jaspamide and Chondramide
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A new method for the synthesis of the tripeptide part of the jaspamide and chondramide alkaloids using a Ugi reaction was developed. The reported approach is considerably shorter than all literature syntheses of the peptide parts of these natural products. A family of peptides with different substituents at the 2-position of the indole moiety was prepared to open up access to analogues of these natural products.
- Zarezin, Danil P.,Shmatova, Olga I.,Kabylda, Adil M.,Nenajdenko, Valentine G.
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p. 4716 - 4722
(2018/09/10)
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- Reduction and Reductive Deuteration of Tertiary Amides Mediated by Sodium Dispersions with Distinct Proton Donor-Dependent Chemoselectivity
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A practical and scalable single electron transfer reduction mediated by sodium dispersions has been developed for the reduction and reductive deuteration of tertiary amides. The chemoselectivity of this method highly depends on the nature of the proton donor. The challenging reduction via C-N bond cleavage has been achieved using Na/EtOH, affording alcohol products, while the use of Na/NaOH/H2O leads to the formation of amines via selective C-O scission. Sodium dispersions with high specific surface areas are crucial to obtain high yields and good chemoselectivity. This new method tolerates a range of tertiary amides. Moreover, the corresponding reductive deuterations mediated by Na/EtOD-d1 and Na/NaOH/D2O afford useful α,α-dideuterio alcohols and α,α-dideuterio amines with an excellent deuterium content.
- Zhang, Bin,Li, Hengzhao,Ding, Yuxuan,Yan, Yuhao,An, Jie
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p. 6006 - 6014
(2018/05/24)
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- Mechanistic Studies on Tryptophan Lyase (NosL): Identification of Cyanide as a Reaction Product
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Tryptophan lyase (NosL) catalyzes the formation of 3-methylindole-2-carboxylic acid and 3-methylindole from l-tryptophan. In this paper, we provide evidence supporting a formate radical intermediate and demonstrate that cyanide is a byproduct of the NosL-catalyzed reaction with l-tryptophan. These experiments require a major revision of the NosL mechanism and uncover an unanticipated connection between NosL and HydG, the radical SAM enzyme that forms cyanide and carbon monoxide from tyrosine during the biosynthesis of the metallo-cluster of the [Fe-Fe] hydrogenase.
- Bhandari, Dhananjay M.,Fedoseyenko, Dmytro,Begley, Tadhg P.
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p. 542 - 545
(2018/01/26)
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- An environmentally friendly protocol for oxidative halocyclization of tryptamine and tryptophol derivatives
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An environmentally friendly and efficient protocol (KX/oxone) for oxidative halocyclization of tryptamine/tryptophol derivatives was developed and demonstrated with 28 examples and concise total synthesis of cyclotryptamine alkaloid protubonines A and B. The distinct advantage of this protocol over all previous methods is that no organic byproduct is generated from a halogenating agent or oxidant, thus greatly reducing the environmental impact of halocyclization and facilitating the post-reaction purification.
- Xu, Jun,Tong, Rongbiao
-
supporting information
p. 2952 - 2956
(2017/07/24)
-
- FUSED THIAZOLOPYRIMIDINE DERIVATIVES AS MNKS INHIBITORS
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The present invention relates to compounds of formulae I and H, or pharmaceutically acceptable salts or esters thereof. Further aspects of the invention relate to pharmaceutical compositions and therapeutic uses of said compounds in the treatment of diseases of uncontrolled cell growth, proliferation and/or survival, inappropriate cellular immune responses, inappropriate cellular inflammatory responses, or neurodegenerative disorders, preferably tauopathies, even more preferably, Alzheimer's disease.
- -
-
Page/Page column 67; 68
(2017/06/12)
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- Reactivity of the nitrogen-centered tryptophanyl radical in the catalysis by the radical SAM enzyme NosL
-
The radical SAM tryptophan (Trp) lyase NosL involved in nosiheptide biosynthesis catalyzes two parallel reactions, converting l-Trp to 3-methyl-2-indolic acid (MIA) and to dehydroglycine and 3-methylindole, respectively. The two parallel reactions diverge from a nitrogen-centered tryptophanyl radical intermediate. Here we report an investigation on the intrinsic reactivity of the tryptophanyl radical using a chemical model study and DFT calculations. The kinetics of the formation and fragmentation of this nitrogen-centered radical in NosL catalysis were also studied in detail. Our analysis explains the intriguing catalytic promiscuity of NosL and highlights the remarkable role this enzyme plays in achieving an energetically highly unfavorable transformation.
- Qianzhu, Haocheng,Ji, Wenjuan,Ji, Xinjian,Chu, Leixia,Guo, Chuchu,Lu, Wei,Ding, Wei,Gao, Jiangtao,Zhang, Qi
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p. 344 - 347
(2017/01/03)
-
- α-Amino Acid-Isosteric α-Amino Tetrazoles
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The synthesis of all 20 common natural proteinogenic and 4 otherα-amino acid-isosteric α-amino tetrazoles has been accomplished, whereby the carboxyl group is replaced by the isosteric 5-tetrazolyl group. The short process involves the use of the key Ugi tetrazole reaction followed by deprotection chemistries. The tetrazole group is bioisosteric to the carboxylic acid and is widely used in medicinal chemistry and drug design. Surprisingly, several of the common α-amino acid-isosteric α-amino tetrazoles are unknown up to now. Therefore a rapid synthetic access to this compound class and non-natural derivatives is of high interest to advance the field.
- Zhao, Ting,Kurpiewska, Katarzyna,Kalinowska-T?us?cik, Justyna,Herdtweck, Eberhardt,D?mling, Alexander
-
supporting information
p. 3009 - 3018
(2016/03/26)
-
- Dearomatization of Indoles via Palladium-Catalyzed Allylic C-H Activation
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The first Pd-catalyzed allylic dearomatization of substituted indoles triggered by C-H bond activation is reported. The presence of a catalytic amount of 2,5-DMBQ is proven to be a key factor for the high yield. This one-pot tandem allylic C-H activation/dearomatization sequence provides a straightforward access to 3,3-disubstituted indolines.
- Zhang, Heng,Hu, Rong-Bin,Liu, Na,Li, Shi-Xia,Yang, Shang-Dong
-
supporting information
p. 28 - 31
(2016/01/15)
-
- Enantioselective Model Synthesis and Progress toward the Putative Structure of Yuremamine
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An enantioselective model synthesis of the 2,3-dihydro-1H-pyrrolo[1,2-a]indole core of the putative structure of yuremamine is reported in 39% overall yield and 96% ee over five steps. The model synthesis leverages enantioselective, rhodium-catalyzed hydroacylation of an N-vinylindole-2-carboxaldehyde as the key step in the installation of the stereochemical triad. An enantioselective synthesis of a densely functionalized dihydropyrroloindolone that maps onto the putative structure of yuremamine is demonstrated in 26% yield and 97% ee over eight steps.
- Ghosh, Avipsa,Bainbridge, David T.,Stanley, Levi M.
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p. 7945 - 7951
(2016/09/12)
-
- Hydroformylation of 2-Alkynylanilines: Toward an Alternative Methodology for the Synthesis of 3-Substituted Indoles
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A potentially viable route for the synthesis of 3-substituted indoles is presented herein. The methodology is based on a regioselective Rh-catalysed hydroformylation of prepared 2-alkyn-1-ylanilines. The requisite 2-alkynylaniline substrates were prepared in high yields (>85 %) using the Pd-catalysed Sonogashira reaction. A catalyst complex that comprises RhI(CO)(PPh3)3 and 1,2-bis(diphenylphosphino)ethane as the ligand allowed the quantitative conversions of the alkynyl substrates with selectivities >75 % for the desired 3-substituted indoles.
- Holzapfel, Cedric,Dasilva, Etelinda,Den Drijver, Laetitia,Bredenkamp, Tyler
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p. 2912 - 2915
(2016/09/28)
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- Novel indole-based sigma-2 receptor ligands: synthesis, structure-affinity relationship and antiproliferative activity
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We report the synthesis and biological evaluation of a series of indole-based σ2 receptor ligands derived from siramesine. In vitro competition binding assays showed that these analogues possessed high to moderate affinity and selectivity for σ2 receptors. Structure-affinity relationship analyses of these indole-based σ2 receptor ligands were performed. In the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, 1a and 1b displayed significant and comparable antiproliferative activity in DU145, MCF7 and C6 cells to siramesine. In cell cycle analyses, compounds 1a, 1b and siramesine were found to induce a G1 phase cell cycle arrest in DU145 cells using flow cytometry. The combination of 5,6-dimethoxyisoindoline scaffold and N-(4-fluorophenyl)indole moiety was identified as a new σ2 receptor ligand deserving further investigation as an antitumor agent.
- Xie, Fang,Kniess, Torsten,Neuber, Christin,Deuther-Conrad, Winnie,Mamat, Constantin,Lieberman, Brian P.,Liu, Boli,Mach, Robert H.,Brust, Peter,Steinbach, J?rg,Pietzsch, Jens,Jia, Hongmei
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p. 1093 - 1103
(2015/06/25)
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- Iridium-catalyzed direct synthesis of tryptamine derivatives from indoles: Exploiting N-protected β-amino alcohols as alkylating agents
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The selective C3-alkylation of indoles with N-protected ethanolamines involving the "borrowing hydrogen" strategy is described. This method provides convenient and sustainable access to several tryptamine derivatives.
- Bartolucci, Silvia,Mari, Michele,Bedini, Annalida,Piersanti, Giovanni,Spadoni, Gilberto
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p. 3217 - 3222
(2015/03/30)
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- Dearomatization of tryptophols via a vanadium-catalyzed asymmetric epoxidation and ring-opening cascade
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An enantioselective epoxidation of tryptophols followed by an intramolecular epoxide opening reaction was realized by chiral vanadium catalysts derived from C2 symmetric bis-hydroxamic acid (BHA) ligands. 3a-Hydroxyfuroindoline derivatives with up to 89% yield and 90% ee were obtained under mild reaction conditions.
- Han, Long,Liu, Chuan,Zhang, Wei,Shi, Xiao-Xin,You, Shu-Li
-
supporting information
p. 1231 - 1233
(2014/02/14)
-
- Synthesis and evaluation of novel 2,3-dihydrobenzo[b][1,4]dioxin- and indolealkylamine derivatives as potential antidepressants
-
A series of 2,3-dihydrobenzo[b][1,4]dioxin- and indolealkylamine derivatives were synthesized and the target compounds were evaluated for their binding affinities at the 5-HT1A receptor and serotonin transporter. Antidepressant-like activities of the compounds were screened using the tail suspension and forced swim tests in mice. Preliminary results indicated that the target compounds exhibited high binding affinities at the 5-HT1A receptor and serotonin transporter, and produced marked antidepressant-like effects. The best example from this study, compound 5, exhibited high binding affinities for the 5-HT1A receptor (Ki = 96 nM) and serotonin transporter (Ki = 9.8 nM). The intrinsic activity of compound 5 showed agonistic property to the 5-HT1A receptor and inhibition of the 5-HT transporter. Furthermore, compound 5 exhibited greater antidepressant efficacy than fluoxetine and showed acceptable pharmacokinetic properties. A series of 3-(2-(4-((2,3-dihydrobenzo[b][1,4]dioxin-3-yl)methyl) piperazin-1-yl)ethyl-1H-indole derivatives were synthesized and the target compounds were evaluated for their antidepressant activities in vitro and in vivo. The compounds described were also evaluated for dual 5-HTT and 5-HT 1A receptor activities.
- Liu, Xin,Wang, Songlin,Chen, Yin,Liu, Xinghua,Xu, Xiangqing,Liu, Bi-Feng,Zhang, Guisen
-
-
- Design, synthesis and evaluation of novel HDAC inhibitors as potential antitumor agents
-
Phenyl imidazolidin-2-one was introduced as the linker for novel HDAC inhibitors. A focused library of 20 compounds was designed and synthesized, among which eight compounds showed equivalent or higher potencies against HDAC1 as compared to vorinostat. In vitro antitumor activity assays in HCT-116, PC-3 and HL-60 cancer cells revealed six compounds with potent antitumor activities, and compound 1o showed 6- to 9-fold higher potencies compared to vorinostat. In an HCT-116 nude mice xenograft model, compound 1o displayed significant antitumor activity in both continuous and intermittent dosing schedules.
- Cheng, Jianjun,Qin, Jihong,Guo, Sihua,Qiu, Hangdeng,Zhong, Yun
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p. 4768 - 4772
(2015/01/09)
-
- Regioselective hydroarylation reactions of C3 electrophilic N-acetylindoles activated by FeCl3: An entry to 3-(Hetero)arylindolines
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A method for the direct and rare umpolung of the 3 position of indoles is reported. The activation of N-acetylindole with iron(III) chloride allows the C-H addition of aromatic and heteroaromatic substrates to the C2-C3 double bond of the indole nucleus to generate a quaternary center at C3 and leads regioselectively to 3-arylindolines. Optimization, scope (50 examples), practicability (gram scale, air atmosphere, room temperature), and mechanistic insights of this process are presented. Synthetic transformations of the indoline products into drug-like compounds are also described.
- Beaud, Rodolphe,Guillot, Regis,Kouklovsky, Cyrille,Vincent, Guillaume
-
supporting information
p. 7492 - 7500
(2014/06/23)
-
- Aluminium chloride hexahydrate (AlCl3.6H2o): An efficient, facile, mild, and highly chemoselective catalytic deprotection of tert-butyldimethylsilyl (tbs) ethers
-
tert-Butyldimethylsilyl (TBS) phenyl / alkyl ethers were cleaved to the corresponding efficiently parent hydroxyl compounds in good yields using catalytic amounts of AlCl3.6H2O by conventional or microwave-assisted heating in methanol or isopropanol solution. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of TBS ethers in the presence of triisopropylsilyl and tert-butyldiphenylsilyl ethers.
- Gonzalez-Calderon, Davir,Benitez-Puebla, Luis J.,Gonzalez-Gonzalez, Carlos A.,Garcia-Eleno, Marco A.,Fuentes-Benitez, Aydee,Cuevas-Yanez, Erick,Corona-Becerril, David,Gonzalez-Romero, Carlos
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p. 1258 - 1265
(2014/04/17)
-
- A novel chemoselective cleavage of (tert-butyl)(dimethyl)silyl (TBS) ethers catalyzed by Ce(SO4)2·4 H2O
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(tert-Butyl)(dimethyl)silyl (tBuMe2Si; TBS) phenyl/alkyl ethers were efficiently cleaved to the corresponding parent hydroxy compounds in good yields using catalytic amounts of Ce(SO4) 2·4 H2O by microwave-assisted or conventional heating in MeOH. Intramolecular and competitive experiments demonstrated the chemoselective deprotection of TBS ethers in the presence of triisopropylsilyl (iPr3Si; TIPS) and (tert-butyl)(diphenyl)silyl ( tBuPh2Si; TBDPS) ethers. Copyright
- González-Calderón, Davir,González-González, Carlos A.,Fuentes-Benítez, Aydeé,Cuevas-Yá?ez, Erick,Corona-Becerril, David,González-Romero, Carlos
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p. 965 - 972
(2014/08/05)
-
- Evaluating a sodium dispersion reagent for the Bouveault-Blanc reduction of esters
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A new sodium dispersion reagent has been evaluated for the reduction of esters. Na-D15, a sodium dispersion with sodium particle size of 5-15 μm, is a nonpyrophoric reagent that can be handled in air. In this study, a broad range of aliphatic ester substrates were reduced to primary alcohols by Na-D15/i-PrOH with good yields. The method compares favorably with modern metal hydride reductions and is much safer and efficient than the traditional Bouveault-Blanc reduction.
- An, Jie,Work, D. Neil,Kenyon, Craig,Procter, David J.
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p. 6743 - 6747
(2014/08/05)
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- Highly chemoselective reduction of amides (primary, secondary, tertiary) to alcohols using SmI2/amine/H2O under mild conditions
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Highly chemoselective direct reduction of primary, secondary, and tertiary amides to alcohols using SmI2/amine/H2O is reported. The reaction proceeds with C-N bond cleavage in the carbinolamine intermediate, shows excellent functional group tolerance, and delivers the alcohol products in very high yields. The expected C-O cleavage products are not formed under the reaction conditions. The observed reactivity is opposite to the electrophilicity of polar carbonyl groups resulting from the nX → πC=O (X = O, N) conjugation. Mechanistic studies suggest that coordination of Sm to the carbonyl and then to Lewis basic nitrogen in the tetrahedral intermediate facilitate electron transfer and control the selectivity of the C-N/C-O cleavage. Notably, the method provides direct access to acyl-type radicals from unactivated amides under mild electron transfer conditions.
- Szostak, Michal,Spain, Malcolm,Eberhart, Andrew J.,Procter, David J.
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supporting information
p. 2268 - 2271
(2014/03/21)
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- A tandem isomerization/prins strategy: Iridium(III)/Bronsted acid cooperative catalysis
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Working together: A mild and efficient isomerization/protonation sequence generates pyran-fused indoles by cooperative catalysis between cationic iridium(III) and Bi(OTf)3. Three distinct cyclization manifolds lead to the corresponding bioactive scaffolds in good yields. In addition, N-substituted indoles can be synthesized enantioselectively in the presence of a chiral phosphate. Copyright
- Lombardo, Vince M.,Thomas, Christopher D.,Scheidt, Karl A.
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supporting information
p. 12910 - 12914
(2014/01/06)
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- Manganese-catalyzed aerobic dehydrogenative cyclization toward ring-fused indole skeletons
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We describe the first example of manganese(iii)-catalyzed aerobic dehydrogenative cyclization producing ring-fused indole skeletons. This catalytic system converts from two C-H bonds of indole and malonate to a C-C bond and produces water as the sole side product. This operationally easy method was extended to an intermolecular cross-dehydrogenative coupling of indole and α-substituted malonate with complete C2-selectivity.
- Oisaki, Kounosuke,Abe, Junpei,Kanai, Motomu
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supporting information
p. 4569 - 4572
(2013/07/26)
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- Direct deamination of primary amines by water to produce alcohols
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Just add water! The title reaction is catalyzed by an acridine-based pincer complex (1, see scheme). This one-step transformation uses water as the only reagent in the absence of additional bases, oxidants, or reductants. Cyclization of 1,4-diaminobutane and 1,6-diaminohexane catalyzed by 1 leads to the formation of pyrrolidine and azepane, respectively. Copyright
- Khusnutdinova, Julia R.,Ben-David, Yehoshoa,Milstein, David
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supporting information
p. 6269 - 6272
(2013/07/19)
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- On the Fischer indole synthesis of 7-ethyltryptophol - Mechanistic and process intensification studies under continuous flow conditions
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7-Ethyltryptophol, a key intermediate in the synthesis of the anti-inflammatory agent etodolac, was produced by Fischer indole synthesis of 2-ethylphenylhydrazine and 2,3-dihydrofuran under continuous flow conditions. The reaction generates several undesired byproducts and therefore product yields could not be improved above 40-50%. The mechanism of this transformation was studied in detail and the structure of the byproducts carefully elucidated. Despite the only moderate product yield, the synthesis of 7-ethyltryptophol by this protocol remains interesting compared to alternative methods and starts from inexpensive reagents. The developed process is executed in an environmentally benign solvent (methanol) and, importantly, the majority of byproducts can be removed from the 7-ethyltryptophol product by a straightforward extraction process.
- Gutmann, Bernhard,Gottsponer, Michael,Elsner, Petteri,Cantillo, David,Roberge, Dominique M.,Kappe, C. Oliver
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p. 294 - 302
(2013/05/08)
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- Fischer indole synthesis in low melting mixtures
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Functionalized indoles are synthezised under mild conditions in a tartaric acid-dimethylurea melt. The melt serves as the solvent and as the catalyst. Under these reaction conditions, sensitive functional groups such as N-Boc, N-Cbz, or azides are stable, and indolenines are obtained regioselectively in excellent yields. The practical use of the method is demonstrated in the synthesis of the hormone melatonin.
- Gore, Sangram,Baskaran, Sundarababu,K?nig, Burkhard
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supporting information
p. 4568 - 4571
(2012/10/30)
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- Preparation of samarium(II) iodide: Quantitative evaluation of the effect of water, oxygen, and peroxide content, preparative methods, and the activation of samarium metal
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Samarium(II) iodide (SmI2) is one of the most important reducing agents in organic synthesis. Synthetic chemistry promoted by SmI2 depends on the efficient and reliable preparation of the reagent. Unfortunately, users can experience difficulties preparing the reagent, and this has prevented realization of the full synthetic potential of SmI2. To provide synthetic chemists with general and reliable methods for the preparation of SmI2, a systematic evaluation of the factors involved in its synthesis has been carried out. Our studies confirm that SmI2 is a user-friendly reagent. Factors such as water, oxygen, and peroxide content in THF have little influence on the synthesis of SmI2. In addition, the use of specialized glovebox equipment or Schlenk techniques is not required for the preparation of SmI2. However, our studies suggest that the quality of samarium metal is an important factor and that the use of low quality metal is the main cause of failed preparations of the reagent. Accordingly, we report a straightforward method for activation of "inactive" samarium metal and demonstrate the broad utility of this protocol through the electron transfer reductions of a range of substrates using SmI2 prepared from otherwise "inactive" metal. An investigation into the stability of SmI2 solutions and an evaluation of commercially available solutions of the reagent is also reported.
- Szostak, Michal,Spain, Malcolm,Procter, David J.
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experimental part
p. 3049 - 3059
(2012/06/01)
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- Electron transfer reduction of carboxylic acids using SmI 2-H2O-Et3N
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The first general method for efficient electron transfer reduction of carboxylic acids has been developed. The protocol using SmI2 - H 2O - Et3N allows for reduction of a variety of carboxylic acids in excellent yields and provides an attractive alternative to processes mediated by reactive alkali metals, lithium aluminum hydride, and boron hydrides. Of broader significance, the method allows acyl radical equivalents to be generated from carboxylic acids under mild reaction conditions.
- Szostak, Michal,Spain, Malcolm,Procter, David J.
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supporting information; experimental part
p. 840 - 843
(2012/04/11)
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- Metabolism and metabolites of dithiocarbamates in the plant pathogenic fungus leptosphaeria maculans
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Synthetic compounds containing a dithiocarbamate group are known to have a variety of biological effects and applications including antifungal, herbicidal, and insecticidal application. Leptosphaeria maculans is a fungal pathogen of crucifers able to detoxify efficiently the only plant natural product containing a dithiocarbamate group, the phytoalexin brassinin. To evaluate the effects of dithiocarbamates on L. maculans, a number of structurally diverse S-methyl dithiocarbamates containing indolyl, biphenyl, and benzimidazolyl moieties were synthesized, and their antifungal activities and metabolism by L. maculans were investigated. All dithiocarbamates were transformed by L. maculans through hydrolysis to the corresponding amines, which were less antifungal than the parent compounds. Two dithiocarbonates were shown to be much less antifungal than the corresponding dithiocarbamates. Results of this investigation indicate that S-methyl dithiocarbamates are not useful inhibitors of L. maculans and that their rates of transformation by L. maculans did not correlate with the antifungal activity of the particular compound.
- Pedras, M. Soledade C.,Sarma-Mamillapalle, Vijay K.
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experimental part
p. 7792 - 7798
(2012/10/08)
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- Electron transfer reduction of unactivated esters using SmI 2-H2O
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The reduction of unactivated esters using samarium diiodide is reported for the first time. The optimised protocol allows for the reduction of primary, secondary and tertiary alkyl esters in excellent yields and is competitive with reductions mediated by metal hydrides and alkali metals.
- Szostak, Michal,Spain, Malcolm,Procter, David J.
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supporting information; experimental part
p. 10254 - 10256
(2011/10/31)
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- Studies towards the total asymmetric synthesis of the pentacyclic indole alkaloid arboflorine: Asymmetric synthesis of a key intermediate
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The synthesis of a plausible key intermediate for a biomimetic asymmetric synthesis of indole alkaloid arboflorine is described. The method featured the use of Ellman's sulfinamide chemistry for the establishment of the first chiral center, and the Polonovski-Potier reaction for the formation of the -aminonitrile moiety. Georg Thieme Verlag Stuttgart New York.
- Du, Yu,Huang, Hui-Ying,Liu, Hui,Ruan, Yuan-Ping,Huang, Pei-Qiang
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supporting information; experimental part
p. 565 - 568
(2011/04/22)
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- Microwave-assisted synthesis of 5-substituted 2-aminothiophenes starting from arylacetaldehydes
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An easy three-step pathway for the synthesis of arylacet-aldehydes from the corresponding carboxylic acids in very high yields is described. Their use as precursors of 5-substituted-2-aminothiophenes is illustrated via a microwave-assisted Gewald reaction. This method allows obtaining the expected compounds in a shorter time and with better yields and purities than the classical procedures. Georg Thieme Verlag Stuttgart - New York.
- Revelant, Germain,Dunand, Sandrine,Hesse, Stephanie,Kirsch, Gilbert
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p. 2935 - 2940
(2011/11/01)
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- NOVEL BENZAMIDE DERIVATIVES
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The present invention provides a novel benzamide derivative or a pharmaceutically acceptable salt thereof, a method for preparing the same, and a 5-HT4 receptor agonist containing the same as an active ingredient. Benzamide derivatives of the present invention have a superior affinity for 5-HT4 receptors, a capability to reduce a gastric emptying time and a low toxicity, and consequently are therapeutically effective for the treatment of a variety of diseases associated with 5-HT4 receptors.
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Page/Page column 21
(2011/11/06)
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