- Structure optimization of positive allosteric modulators of GABAB receptors led to the unexpected discovery of antagonists/potential negative allosteric modulators
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Positive allosteric modulators (PAMs) of GABAB receptor represent an interesting alternative to receptor agonists such as baclofen, as they act on the receptor in a more physiological way and thus are devoid of the side effects typically exerted by the agonists. Based on our interest in the identification of new GABAB receptor PAMs, we followed a merging approach to design new chemotypes starting from selected active compounds, such as GS39783, rac-BHFF, and BHF177, and we ended up with the synthesis of four different classes of compounds. The new compounds were tested alone or in the presence of 10 μM GABA using [35S]GTPγS binding assay to assess their functionality at the receptor. Unexpectedly, a number of them significantly inhibited GABA-stimulated GTPγS binding thus revealing a functional switch with respect to the prototype molecules. Further studies on selected compounds will clarify if they act as negative modulators of the receptor or, instead, as antagonists at the orthosteric binding site.
- Mugnaini, Claudia,Brizzi, Antonella,Mostallino, Rafaela,Castelli, Maria Paola,Corelli, Federico
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- Titanium-Catalyzed Hydroaminoalkylation of Ethylene
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The first examples of titanium-catalyzed hydroaminoalkylation reactions of ethylene with secondary amines are presented. The reactions can be achieved with various titanium catalysts and they do not require the use of high pressure equipment. In addition, the first solid-state structure of a titanapyrrolidine that is formed by insertion of an alkene into the Ti?C bond of a titanaaziridine is reported.
- Rosien, Michael,T?ben, Iris,Schmidtmann, Marc,Beckhaus, Rüdiger,Doye, Sven
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supporting information
p. 2138 - 2142
(2020/02/05)
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- Direct Aryl C?H Amination with Primary Amines Using Organic Photoredox Catalysis
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The direct catalytic C?H amination of arenes is a powerful synthetic strategy with useful applications in pharmaceuticals, agrochemicals, and materials chemistry. Despite the advances in catalytic C?H functionalization, the use of aliphatic amine coupling partners is limited. Described herein is the construction of C?N bonds, using primary amines, by direct C?H functionalization with an acridinium photoredox catalyst under an aerobic atmosphere. A wide variety of primary amines, including amino acids and more complex amines are competent coupling partners. Various electron-rich aromatics and heteroaromatics are useful scaffolds in this reaction, as are complex, biologically active arenes. We also describe the ability to functionalize arenes that are not oxidized by an acridinium catalyst, such as benzene and toluene, thus supporting a reactive amine cation radical intermediate.
- Margrey, Kaila A.,Levens, Alison,Nicewicz, David A.
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supporting information
p. 15644 - 15648
(2017/11/20)
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- Convenient N-Alkylation of amines using an effective magnetically separable supported ionic liquid containing an anionic polyoxometalate
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Abstract: An effective synthesis of anion-exchanged supported ionic liquid using magnetically separable nanoparticles and its catalytic effect on N-alkylation reactions is described. Anionic polyoxometalate derivative was used in the anion-exchange step in catalyst design. The catalytic system can be easily separated from the reaction mixture with external magnetic field and recycled in subsequent reactions. In order to evaluate catalyst repeatability, N-alkylation of some more amines such as Aniline, 4-aminobenzenesulfonamide, 4-methoxyaniline, 2-aminopyrimidin and 4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine in the presence of recoverable catalyst was successfully examined in this article. In addition, pramipexole dihydrochloride as an active pharmaceutical ingredient was successfully synthesized using the catalytic system. The structure of catalyst was determined by infrared spectroscopy, X-ray powder diffraction, and scanning electron microscope techniques. The structure of organic products was determined by 1H NMR, 13C NMR, infrared and Mass spectroscopy. Graphical Abstract: [Figure not available: see fulltext.]
- Ghasemi, Mohammad Hadi,Kowsari, Elaheh
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p. 1957 - 1968
(2017/02/15)
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- A sound shielding through the level three-stage amine instead new method should be secondary amine
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The invention discloses a novel method for preparing secondary amine by a reaction of primary amine and tertiary amine. The method comprises the following steps of 1, adding primary amine and tertiary amine into a reaction container according to a mole ratio of primary amine to tertiary amine of 1: 3, adding [(Bt)2*Ir*P(nBu)3]OTf as a catalyst (wherein Bt represents phenylbenzothiazole) into the reaction container, adding an organic solvent into the reaction container, and carrying out a reaction process at a temperature of 120-160 DEG C for 6-12h, wherein a mole ratio of primary amine, tertiary amine to catalyst is 1: 3: 0.01, and 2, carrying out purification by a silica gel column of 200-300 meshes, pre-leaching the silica gel column by 20-50mL of petroleum ether, carrying out elution on the leacheate at a leacheate flowing rate of 1-2mL/min for 3-6h so that the solvent is removed and the corresponding secondary amine product is obtained. A research result shows that the novel method for producing secondary amine by a reaction of primary amine and tertiary amine has the characteristics of mild conditions, high conversion rate and no pollutant. The method solves the problems of the existing secondary amine synthesis method and improves secondary amine synthesis.
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Paragraph 0045; 0046; 0047
(2017/06/02)
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- d-Glucose: An Efficient Reducing Agent for a Copper(II)-Mediated Arylation of Primary Amines in Water
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A copper-catalyzed Ullmann-type amination with primary amines in water with a combination of copper(II) triflate [Cu(OTf)2], dipivaloylmethane, and d-glucose is reported. The mild conditions and the use of an inexpensive catalyst as well as a renewable feedstock (d-glucose and the surfactant TPGS-750-M, which is derived from vitamin E) make this protocol a safe and convenient strategy for efficient C?N bond formation. This easy-to-handle procedure is extremely competitive compared to palladium-based reactions and may be used to synthesize N-containing molecules, such as drugs or organic light-emitting diodes (OLEDs).
- Bollenbach, Maud,Wagner, Patrick,Aquino, Pedro G. V.,Bourguignon, Jean-Jacques,Bihel, Frédéric,Salomé, Christophe,Schmitt, Martine
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p. 3244 - 3249
(2016/11/29)
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- Assembly of substituted 2-alkylquinolines by a sequential palladium-catalyzed Ci-N and Ci-C bond formation
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Diversity: A range of substituted 2-alkylquinolines can be prepared in a general and efficient synthetic approach that employs mild reaction conditions (see scheme). The synthesis is based on a sequential palladium-catalyzed Ci-N and Ci-C bond formation, followed by palladium-catalyzed aromatization, and results in the formation of the desired compounds in one step. Copyright
- Matsubara, Yoshio,Hirakawa, Saori,Yamaguchi, Yoshihiro,Yoshida, Zen-Ichi
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experimental part
p. 7670 - 7673
(2011/10/05)
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- Selective copper-promoted cross-coupling of aromatic amines with alkyl boronic acids
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A simple copper-promoted N-monoalkylation of anilines that utilizes alkyl boronic acids as the alkylating partner is presented. The reaction is carried out in refluxing dioxane, and it allows a number of structurally and electronically diverse anilines to be functionalized in a single step. A broad study was carried out to demonstrate the utility of this new methodology for the preparation of phenethylanilines.
- Larrosa, Marta,Guerrero, César,Rodríguez, Ramón,Cruces, Jacobo
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supporting information; experimental part
p. 2101 - 2105
(2010/10/03)
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- Iridium-catalysed amine alkylation with alcohols in water
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Amines have been directly alkylated with alcohols using 1 mol% [Cp*IrI2]2 catalyst in water in the absence of base or other additives. The Royal Society of Chemistry 2010.
- Saidi, Ourida,Blacker, A. John,Farah, Mohamed M.,Marsden, Stephen P.,Williams, Jonathan M. J.
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supporting information; experimental part
p. 1541 - 1543
(2010/06/12)
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- Conjugated imines and iminium salts as versatile acceptors of nucleophiles
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Growing interests in nitrogen-containing molecules involving bioactive and functional materials have stimulated the recent development of synthetic methodologies where nucleophilic addition reactions to imino carbons are utilized in crucial steps. This article summarizes double nucleophilic addition reactions with α,β-unsaturated aldimines, addition reactions using alkynyl imines, "umpoled" reactions of α-imino esters, and the use of iminium salts as reactive electrophiles. The Royal Society of Chemistry 2009.
- Shimizu, Makoto,Hachiya, Iwao,Mizota, Isao
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scheme or table
p. 874 - 889
(2009/07/10)
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- Copper catalyzed coupling of aryl chlorides, bromides and iodides with amines and amides
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A copper(i) catalyzed procedure for carbon-nitrogen bond formation utilizing aryl halides and either amines, including amino acids and diphenylamine, or aliphatic and aromatic amides is described. The Royal Society of Chemistry.
- Xu, Hanhui,Wolf, Christian
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supporting information; experimental part
p. 1715 - 1717
(2009/08/08)
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- One-pot reductive monoalkylation of nitro aryls with hydrogen over Pd/C
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A range of different nitro aryls were converted in one-pot to the corresponding secondary alkyl amino aryls in good to excellent yields by using aldehydes as alkyl source and hydrogen over Pd/C (10%) as reducing agent. In all examples, but one, the second
- Sydnes, Magne O.,Isobe, Minoru
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p. 1199 - 1202
(2008/09/17)
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- Bis(cyclohexanone) oxalyldihydrazone/copper(II) oxide - A novel and efficient catalytic system for ullmann-type C-N coupling in pure water
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Animations of aryl halides were conducted under fast copper- bis(cyclohexanone) oxalyldihydrazone catalysis in pure water with both temperature-controlled microwave heating and traditional heating. With a reaction time of five minutes under microwave heating at 130 °C or at reflux for 10 hours, both electron-rich and electron-deficient aryl halides reacted with various amines to provide fair to good yields of the corresponding anilines. Georg Thieme Verlag Stuttgart.
- Zhu, Xinhai,Ma, Yan,Su, Li,Song, Huacan,Chen, Gong,Liang, Dacheng,Wan, Yiqian
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p. 3955 - 3962
(2008/03/11)
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- Reductive monoalkylation of aromatic and aliphatic nitro compounds and the corresponding amines with nitriles
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(Chemical Equation Presented) A simple, selective, rapid, and efficient procedure for the synthesis of secondary amines from the reductive alkylation of either aliphatic or aromatic nitro compounds and the corresponding amines is reported. Ammonium formate is used as the hydrogen source and Pd/C as the hydrogen transfer catalyst. The reaction is carried out at room temperature. The rate differences for the preferential formation of secondary over tertiary products are due to both steric and electronic factors.
- Nacario, Ruel,Kotakonda, Shailaja,Fouchard, David M. D.,Tillekeratne, L. M. Viranga,Hudson, Richard A.
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p. 471 - 474
(2007/10/03)
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- Iminomalonate as a convenient electrophilic amination reagent for grignard reagents
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Diethyl 2-[N-(p-methoxyphenyl)imino]malonate underwent amination reactions with alkyl Grignard reagents to give N-aklylation products in good yields. The obtained N-alkylation products were readily converted into N-alkyl-panisidines by the oxidative removal of the malonate moiety. The p-methoxyphenyl group was subsequently deprotected to give primary amines.
- Niwa, Yasuki,Takayama, Kazuki,Shimizu, Makoto
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p. 1819 - 1825
(2007/10/03)
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- Electrophilic amination with iminomalonate
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Diethyl N-anisyliminomalonate has been found to be an excellent electrophilic amination reagent for Grignard reagents to give N-alkylated products in good yields, and subsequent air oxidation affords N-alkylanisidines.
- Niwa, Yasuki,Takayama, Kazuki,Shimizu, Makoto
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p. 5473 - 5476
(2007/10/03)
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- High-pressure alkylation of azomethines 1. Synthesis of N-monoalkylanilines
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Reaction of anils with alkyl halides under high pressure (10 kbar) was studied. Alkylation in polar media (dioxane or acetonitrile) followed by hydrolysis yields pure N-monoalkylanilines in high yields. Optimum conditions for high-pressure alkylation were found.
- Agafonov,Dudin,Preobrazhenskii,Zhulin
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p. 1005 - 1007
(2007/10/03)
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