- In Situ Formation of Cationic π-Allylpalladium Precatalysts in Alcoholic Solvents: Application to C-N Bond Formation
-
We report an efficient Buchwald-Hartwig cross-coupling reaction in alcoholic solvent, in which a low catalyst loading showed excellent performance for coupling aryl halides (I, Br, and Cl) with a broad set of amines, amides, ureas, and carbamates under mild conditions. Mechanistically speaking, in a protic and polar medium, extremely bulky biarylphosphine ligands interact with the dimeric precatalyst [Pd(π-(R)-allyl)Cl]2 to form the corresponding cationic complexes [Pd(π-(R)-allyl)(L)]Cl in situ and spontaneously. The resulting precatalyst further evolves under basic conditions into the corresponding L-Pd(0) catalyst, which is commonly employed for cross-coupling reactions. This mechanistic study highlights the prominent role of alcoholic solvents for the formation of the active catalyst.
- Steinsoultz, Philippe,Bailly, Aurélien,Wagner, Patrick,Oliva, Estefania,Schmitt, Martine,Grimaud, Laurence,Bihel, Frédéric
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p. 560 - 567
(2022/01/03)
-
- N-pyridinylbenzamides: an isosteric approach towards new antimycobacterial compounds
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A series of N-pyridinylbenzamides was designed and prepared to investigate the influence of isosterism and positional isomerism on antimycobacterial activity. Comparison to previously published isosteric N-pyrazinylbenzamides was made as an attempt to draw structure–activity relationships in such type of compounds. In total, we prepared 44 different compounds, out of which fourteen had minimum inhibitory concentration (MIC) values against Mycobacterium tuberculosis H37Ra below 31.25?μg/ml, most promising being N-(5-chloropyridin-2-yl)-3-(trifluoromethyl)benzamide (23) and N-(6-chloropyridin-2-yl)-3-(trifluoromethyl)benzamide (24) with MIC?=?7.81?μg/ml (26?μm). Five compounds showed broad-spectrum antimycobacterial activity against M. tuberculosis H37Ra, M. smegmatis and M. aurum. N-(pyridin-2-yl)benzamides were generally more active than N-(pyridin-3-yl)benzamides, indicating that N-1 in the parental structure of N-pyrazinylbenzamides might be more important for antimycobacterial activity than N-4. Marginal antibacterial and antifungal activity was observed for title compounds. The hepatotoxicity of title compounds was assessed in vitro on hepatocellular carcinoma cell line HepG2, and they may be considered non-toxic (22 compounds with IC50 over 200?μm).
- Nawrot, Daria,Suchánková, Eli?ka,Jan?ourek, Ond?ej,Kone?ná, Klára,Bárta, Pavel,Dole?al, Martin,Zitko, Jan
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p. 686 - 700
(2020/11/30)
-
- Direct Amidation of Esters by Ball Milling**
-
The direct mechanochemical amidation of esters by ball milling is described. The operationally simple procedure requires an ester, an amine, and substoichiometric KOtBu and was used to prepare a large and diverse library of 78 amide structures with modest to excellent efficiency. Heteroaromatic and heterocyclic components are specifically shown to be amenable to this mechanochemical protocol. This direct synthesis platform has been applied to the synthesis of active pharmaceutical ingredients (APIs) and agrochemicals as well as the gram-scale synthesis of an active pharmaceutical, all in the absence of a reaction solvent.
- Barreteau, Fabien,Battilocchio, Claudio,Browne, Duncan L.,Godineau, Edouard,Leitch, Jamie A.,Nicholson, William I.,Payne, Riley,Priestley, Ian
-
supporting information
p. 21868 - 21874
(2021/09/02)
-
- N-Ammonium Ylide Mediators for Electrochemical C-H Oxidation
-
The site-specific oxidation of strong C(sp3)-H bonds is of uncontested utility in organic synthesis. From simplifying access to metabolites and late-stage diversification of lead compounds to truncating retrosynthetic plans, there is a growing need for new reagents and methods for achieving such a transformation in both academic and industrial circles. One main drawback of current chemical reagents is the lack of diversity with regard to structure and reactivity that prevents a combinatorial approach for rapid screening to be employed. In that regard, directed evolution still holds the greatest promise for achieving complex C-H oxidations in a variety of complex settings. Herein we present a rationally designed platform that provides a step toward this challenge using N-ammonium ylides as electrochemically driven oxidants for site-specific, chemoselective C(sp3)-H oxidation. By taking a first-principles approach guided by computation, these new mediators were identified and rapidly expanded into a library using ubiquitous building blocks and trivial synthesis techniques. The ylide-based approach to C-H oxidation exhibits tunable selectivity that is often exclusive to this class of oxidants and can be applied to real-world problems in the agricultural and pharmaceutical sectors.
- Saito, Masato,Kawamata, Yu,Meanwell, Michael,Navratil, Rafael,Chiodi, Debora,Carlson, Ethan,Hu, Pengfei,Chen, Longrui,Udyavara, Sagar,Kingston, Cian,Tanwar, Mayank,Tyagi, Sameer,McKillican, Bruce P.,Gichinga, Moses G.,Schmidt, Michael A.,Eastgate, Martin D.,Lamberto, Massimiliano,He, Chi,Tang, Tianhua,Malapit, Christian A.,Sigman, Matthew S.,Minteer, Shelley D.,Neurock, Matthew,Baran, Phil S.
-
supporting information
p. 7859 - 7867
(2021/05/26)
-
- Compound containing bipyrazole ring, intermediate thereof and application thereof
-
The invention discloses a compound containing a bipyrazole ring, and an intermediate and application thereof. The invention provides the compound containing a bipyrazole ring, as shown in a formula Iwhich is described in the specification. The compound can be used as a ligand, is high in selectivity, and is suitable for the application range of amide in C-N coupling and the C-C coupling reactionof arylboronic acid and aryl chloride, especially coupling with aryl chloride.
- -
-
Paragraph 0284-0286
(2020/05/14)
-
- Preparation method of compound containing bipyrazole ring and intermediate thereof
-
The invention discloses a preparation method of a compound containing a bipyrazole ring and an intermediate of the compound. The preparation method of a bipyrazole ring-containing compound as shown ina formula I comprises the following steps: (1) adding alkali into a mixture of a bipyrazole ring compound as shown in a formula I-1 and a solvent for replacement reaction to obtain a mixed system; and (2) adding an organic phosphorus compound shown as a formula I-2 into the mixed system in the step (1), and carrying out a phosphonation reaction shown in the specification, so as to obtain the bipyrazole ring-containing compound shown as the formula I, wherein R1 and R2 are independently a C1-C6 alkyl group, a C3-C8 cycloalkyl group and a phenyl group, R3 is a C1-C6 alkyl group, and X is halogen. The prepared compound containing a bipyrazole ring can be used as a ligand, and is suitable for the application range of amide in C-N coupling and the C-C coupling reaction of arylboronic acid andaryl chloride.
- -
-
Paragraph 0284-0286
(2020/05/14)
-
- Synthesis of 2-Amino-1,3-dienes from Propargyl Carbonates via Palladium-Catalyzed Carbon-Nitrogen Bond Formation
-
A catalytic method to synthesize 1,3,-dienes from propargylic precursors is reported. This palladium-catalyzed carbon-nitrogen bond-forming reaction furnishes 2-amino-1,3-dienes in excellent yields (up to 98%) and shows a broad tolerance to functional group diversity. The reaction has been demonstrated for over 30 amine substrates, including anilines and indoles, and proceeds under mild neutral conditions. The resulting 1,3-dienes are of great synthetic interest because of their further reaction potential.
- O'Broin, Calvin Q.,Guiry, Patrick J.
-
supporting information
p. 879 - 883
(2020/02/04)
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- Switching from biaryl formation to amidation with convoluted polymeric nickel catalysis
-
A stable, reusable, and insoluble poly(4-vinyl-pyridine) nickel catalyst (P4VP-NiCl2) was prepared through the molecular convolution of poly(4-vinylpyridine) (P4VP) and nickel chloride. We proposed a coordination structure of the Ni center in the precatalyst based on elemental analysis and Ni K-edge XANES, and we confirmed that it is consistent with Ni K-edge EXAFS. The Suzuki?Miyaura-type coupling of aryl halides and arylboronic esters proceeded using P4VP-NiCl2 (0.1 mol % Ni) to give the corresponding biaryl compounds in up to 94% yield. Surprisingly, when the same reaction of aryl halides and arylboronic acid/ester was carried out in the presence of amides, the amidation proceeded predominantly to give the corresponding arylamides in up to 99% yield. In contrast, the reaction of aryl halides and amides in the absence of arylboronic acid/ester did not proceed. P4VP-NiCl2 successfully catalyzed the lactamization for preparing phenanthridinone. P4VP-NiCl2 was reused five times without significant loss of catalytic activity. Pharmaceuticals, natural products, and biologically active compounds were synthesized efficiently using P4VPNiCl2 catalysis. Nickel contamination in the prepared pharmaceutical compounds was not detected by ICP-MS analysis. The reaction was scaled to multigrams without any loss of chemical yield. Mechanistic studies for both Suzuki?Miyaura and amidation were performed.
- Sen, Abhijit,Dhital, Raghu N.,Sato, Takuma,Ohno, Aya,Yamada, Yoichi M.A.
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p. 14410 - 14418
(2020/12/21)
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- Clickable coupling of carboxylic acids and amines at room temperature mediated by SO2F2: A significant breakthrough for the construction of amides and peptide linkages
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The construction of amide bonds and peptide linkages is one of the most fundamental transformations in all life processes and organic synthesis. The synthesis of structurally ubiquitous amide motifs is essential in the assembly of numerous important molecules such as peptides, proteins, alkaloids, pharmaceutical agents, polymers, ligands and agrochemicals. A method of SO2F2-mediated direct clickable coupling of carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner (>110 examples, >90% yields in most cases). The direct click reactions of acids and amines on a gram scale are also demonstrated using an extremely easy work-up and purification process of washing with 1 M aqueous HCl to provide the desired amides in greater than 99% purity and excellent yields.
- Wang, Shi-Meng,Zhao, Chuang,Zhang, Xu,Qin, Hua-Li
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p. 4087 - 4101
(2019/04/30)
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- Optimization of Synthetically Versatile Pyridylidene Amide Ligands for Efficient Iridium-Catalyzed Water Oxidation
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The synthetic versatility of pyridylidene amide (PYA) ligands has been exploited to prepare and evaluate a diverging series of iridium complexes containing C,N-bidentate chelating aryl-PYA ligands for water oxidation catalysis. The phenyl-PYA lead structu
- Navarro, Miquel,Smith, Christene A.,Li, Mo,Bernhard, Stefan,Albrecht, Martin
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p. 6386 - 6398
(2018/04/30)
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- Vanadium-Catalyzed Oxidative C(CO)-C(CO) Bond Cleavage for C-N Bond Formation: One-Pot Domino Transformation of 1,2-Diketones and Amidines into Imides and Amides
-
A novel vanadium-catalyzed one-pot domino reaction of 1,2-diketones with amidines has been identified that enables their transformation into imides and amides. The reaction proceeds by dual acylation of amidines via oxidative C(CO)-C(CO) bond cleavage of 1,2-diketones to afford N,N′-diaroyl-N-arylbenzamidine intermediates. In the reaction, these intermediates are easily hydrolyzed into imides and amides through vanadium catalysis. This method provides a practical, simple, and mild synthetic approach to access a variety of imides as well as amides in high yields. Moreover, one-step construction of imide and amide bonds with a long-chain alkyl group is an attractive feature of this protocol.
- Digwal, Chander Singh,Yadav, Upasana,Ramya, P. V. Sri,Sana, Sravani,Swain, Baijayantimala,Kamal, Ahmed
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p. 7332 - 7345
(2017/07/26)
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- Compound I and (R)- 3 - amino piperidine hydrochloride II, its preparation method and its application in the synthesis of advantage geleg sandbank
-
The invention discloses a preparation method of 3-aminopiperidine and its derivative with optical activity and an application of the compound and its derivative in synthesis of a dipeptidyl peptidase-IV inhibitor Linagliptin. According to the preparation
- -
-
Paragraph 0084-0086
(2017/10/22)
-
- Development of Method for Amide Bond Formation via Metal-Free Aerobic Oxidative Amination of Aldehydes
-
The present invention relates to a method for preparing an amide compound by using an aerobic oxidative amination reaction using an oxygen resource as an oxidizer in an organic solvent without metal by using a cyanide as a catalyst. An expensive metal catalyst is not needed to prepare the amide compound of the present invention. Therefore, the amide compound does not have a problem of toxicity caused by remaining metal and has excellent economic efficiency of atoms. Moreover, the amide compound can be used for industries in an easy manner because complicated processes such as a strong acid, low temperatures, and anhydrous conditions are not needed to prepare the amide compound.COPYRIGHT KIPO 2015
- -
-
Paragraph 0094; 0134; 0135
(2016/11/17)
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- Formation of Amides from Imines via Cyanide-Mediated Metal-Free Aerobic Oxidation
-
A new protocol for the direct formation of amides from imines derived from aromatic aldehydes via metal-free aerobic oxidation in the presence of cyanide is described. This protocol was applicable to various aldimines, and the desired amides were obtained in moderate to good yields. Mechanistic studies suggested that this aerobic oxidative amidation might proceed via the addition of cyanide to imines followed by proton transfer from carbon to nitrogen in the original imines, leading to carbanions of α-amino nitriles, which undergo subsequent oxidation with molecular oxygen in air to provide the desired amide compounds.
- Seo, Hong-Ahn,Cho, Yeon-Ho,Lee, Ye-Sol,Cheon, Cheol-Hong
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p. 11993 - 11998
(2016/01/09)
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- Copper-Catalyzed N-Benzoylation of Amines via Aerobic C-C Bond Cleavage
-
A general copper/air catalytic system for selectively oxidative C-C bond cleavage of 1,2-diarylethan-1-one has been developed, giving aromatic aldehydes and N-benzoylation products of various amines in moderate to excellent yields. This research provides an alternative approach for the N-benzoylation of amine in mild and neutral conditions.
- Fan, Wenyou,Yang, Youqing,Lei, Jianhua,Jiang, Qijian,Zhou, Wang
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p. 8782 - 8789
(2015/09/15)
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- P2Et Phosphazene: A Mild, Functional Group Tolerant Base for Soluble, Room Temperature Pd-Catalyzed C-N, C-O, and C-C Cross-Coupling Reactions
-
The non-nucleophilic organic superbase P2Et phosphazene can enable a broad range of palladium-catalyzed cross-coupling reactions, including C-C, C-N, and C-O couplings of aryl chlorides, bromides, and iodides at room temperature. The mildness a
- Buitrago Santanilla, Alexander,Christensen, Melodie,Campeau, Louis-Charles,Davies, Ian W.,Dreher, Spencer D.
-
supporting information
p. 3370 - 3373
(2015/07/15)
-
- Effective nitration of anilides and acrylamides by tert-butyl nitrite
-
Nitro compounds are important intermediates in synthetic organic chemistry and the chemical industry. Herein, the efficient copper-catalyzed [10% Cu(NO3)2·3H2O] nitration of anilides was developed by using TBN (tert-butyl nitrite) as a nitrating reagent to give the corresponding nitro-substituted aromatic products in good to excellent yields. The use of TBN also led to the selective nitration of acrylamides at room temperature to afford only the (E) isomer of the nitration product. A series of anilides and acrylamides with a broad array of functional groups were well-tolerated by this procedure. This synthetic method has many advantages, which include inexpensive starting materials, mild reaction conditions, a fast reaction rate, and high yields. A mechanistic investigation indicates that a nitro radical, which is generated from the thermal homolysis of TBN, is involved in the two nitration processes. The efficient nitration of both anilides and acrylamides was achieved by using TBN (tert-butyl nitrite) as a metal-free nitrating reagent. This synthetic method has many advantages such as mild reaction conditions, a fast reaction rate, good to excellent yields, and a broad substrate scope. Our investigation indicates that a nitro radical is involved in the reaction mechanism.
- Ji, Yi-Fei,Yan, Hong,Jiang, Qi-Bai
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p. 2051 - 2060
(2015/03/18)
-
- Molybdenum-mediated desulfurization of dhiols and disulfides
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We have successfully achieved the molybdenum hexacarbonyl [Mo(CO) 6] mediated desulfurization of thiols and disulfides. In this reaction, the sulfhydryl (SH) mercapto groups of aryl, benzyl, primary and secondary alkyl thiols, and S-S single bonds of disulfides can be removed. This reaction has high functional group tolerance and is not affected by steric hindrance. The results of the reactions in acetone-d 6 suggest that the sources of hydrogen in the thiol and disulfide desulfurizations are the hydrogen atom(s) of a sulfhydryl group and acetone (solvent), respectively, and that the desulfurization proceeds via the formation of an organomolybdenum species. Georg Thieme Verlag Stuttgart. New York.
- Wang, Zhen,Kuninobu, Yoichiro,Kanai, Motomu
-
supporting information
p. 1869 - 1872
(2014/08/18)
-
- Fragment-based design of 3-aminopyridine-derived amides as potent inhibitors of human nicotinamide phosphoribosyltransferase (NAMPT)
-
The fragment-based identification of two novel and potent biochemical inhibitors of the nicotinamide phosphoribosyltransferase (NAMPT) enzyme is described. These compounds (51 and 63) incorporate an amide moiety derived from 3-aminopyridine, and are thus structurally distinct from other known anti-NAMPT agents. Each exhibits potent inhibition of NAMPT biochemical activity (IC 50 = 19 and 15 nM, respectively) as well as robust antiproliferative properties in A2780 cell culture experiments (IC50 = 121 and 99 nM, respectively). However, additional biological studies indicate that only inhibitor 51 exerts its A2780 cell culture effects via a NAMPT-mediated mechanism. The crystal structures of both 51 and 63 in complex with NAMPT are also independently described.
- Dragovich, Peter S.,Zhao, Guiling,Baumeister, Timm,Bravo, Brandon,Giannetti, Anthony M.,Ho, Yen-Ching,Hua, Rongbao,Li, Guangkun,Liang, Xiaorong,Ma, Xiaolei,O'Brien, Thomas,Oh, Angela,Skelton, Nicholas J.,Wang, Chengcheng,Wang, Weiru,Wang, Yunli,Xiao, Yang,Yuen, Po-Wai,Zak, Mark,Zhao, Qiang,Zheng, Xiaozhang
-
p. 954 - 962
(2014/02/14)
-
- T-BuXPhos: A highly efficient ligand for Buchwald-Hartwig coupling in water
-
An efficient and versatile 'green' catalytic system for the Buchwald-Hartwig cross-coupling reaction in water is reported. In an aqueous micellar medium, the combination of t-BuXPhos with [(cinnamyl)PdCl]2 showed excellent performance for coupling arylbromides or chlorides with a large set of amines, amides, ureas and carbamates. The method is functional-group tolerant, proceeds smoothly (30 to 50 °C) and provides rapid access to the target compounds in good to excellent isolated yields. When applied to the synthesis of a known NaV1.8 modulator, this method led to a significant improvement of the E-factor in comparison with classical organic synthesis. the Partner Organisations 2014.
- Wagner, Patrick,Bollenbach, Maud,Doebelin, Christelle,Bihel, Frederic,Bourguignon, Jean-Jacques,Salome, Christophe,Schmitt, Martine
-
supporting information
p. 4170 - 4178
(2014/09/29)
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- Practical preparation of challenging amides from non-nucleophilic amines and esters under flow conditions
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A fast and efficient protocol for the formation of amides from low nucleophilic amines and esters in flow is described. Products were obtained in good to excellent yields and with the advantage of simultaneous mixing of all reagents at once, avoiding steps for intermediate formation. The protocol is also suitable to be combined with ester synthesis, resulting in the preparation of amides in-line from haloarenes. This journal is
- Vrijdag, Johannes L.,Delgado, Francisca,Alonso, Nerea,De Borggraeve, Wim M.,Prez-Macias, Natalia,Alczar, Jesus
-
supporting information
p. 15094 - 15097
(2014/12/11)
-
- BippyPhos: A single ligand with unprecedented scope in the Buchwald-Hartwig amination of (hetero)aryl chlorides
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Over the past two decades, considerable attention has been given to the development of new ligands for the palladium-catalyzed arylation of amines and related NH-containing substrates (i.e., Buchwald-Hartwig amination). The generation of structurally diverse ligands, by research groups in both academia and industry, has facilitated the accommodation of sterically and electronically divergent substrates including ammonia, hydrazine, amines, amides, and NH heterocycles. Despite these achievements, problems with catalyst generality persist and access to multiple ligands is necessary to accommodate all of these NH-containing substrates. In our quest to address this significant limitation we identified the BippyPhos/[Pd(cinnamyl)Cl]2 catalyst system as being capable of catalyzing the amination of a variety of functionalized (hetero)aryl chlorides, as well as bromides and tosylates, at moderate to low catalyst loadings. The successful transformations described herein include primary and secondary amines, NH heterocycles, amides, ammonia and hydrazine, thus demonstrating the largest scope in the NH-containing coupling partner reported for a single Pd/ligand catalyst system. We also established BippyPhos/ [Pd(cinnamyl)Cl]2 as exhibiting the broadest demonstrated substrate scope for metal-catalyzed cross-coupling of (hetero)aryl chlorides with NH indoles. Furthermore, the remarkable ability of BippyPhos/[Pd(cinnamyl)Cl] 2 to catalyze both the selective monoarylation of ammonia and the N-arylation of indoles was exploited in the development of a new one-pot, two-step synthesis of N-aryl heterocycles from ammonia, ortho- alkynylhalo(hetero)arenes and (hetero) aryl halides through tandem N-arylation/hydroamination reactions. Although the scope in the NH-containing coupling partner is broad, BippyPhos/[Pd(cinnamyl)Cl]2 also displays a marked selectivity profile that was exploited in the chemoselective monoarylation of substrates featuring two chemically distinct NH-containing moieties.
- Crawford, Sarah M.,Lavery, Christopher B.,Stradiotto, Mark
-
supporting information
p. 16760 - 16771
(2014/01/06)
-
- Direct N-cyclopropylation of secondary acyclic amides promoted by copper
-
The N-cyclopropylation of aromatic and aliphatic secondary acyclic amides, known to be poor nucleophiles, has been accomplished using a simple and cheap copper system. The corresponding tertiary acyclic amides, which constitute a wide family of biologically active compounds, have been obtained in good to excellent yields.
- Racine, Emilie,Monnier, Florian,Vors, Jean-Pierre,Taillefer, Marc
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supporting information
p. 7412 - 7414
(2013/09/23)
-
- Tert-butoxide-assisted amidation of esters under green conditions
-
Efficient and green amidation reactions are of great importance. In this work, we demonstrate the tert-butoxide-assisted amidation of esters with amines under ambient conditions. Aliphatic and/or aromatic esters were converted into the corresponding amides under mild conditions in good to excellent yields. It is noteworthy that the reaction is highly efficient, rapid, versatile, green and economical, and will find great practical application in organic synthesis, biochemistry, and industrial chemistry. Georg Thieme Verlag Stuttgart. New York.
- Kim, Bo Ram,Lee, Hyung-Geun,Kang, Seung-Beom,Sung, Gi Hyeon,Kim, Jeum-Jong,Park, Jong Keun,Lee, Sang-Gyeong,Yoon, Yong-Jin
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experimental part
p. 42 - 50
(2012/03/26)
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- AlMe3-promoted formation of amides from acids and amines
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In the presence of AlMe3, amines can be directly coupled with acids through dimethylaluminum amide intermediates to form the corresponding amides. A wide range of amines and acids including less nucleophilic amines, bulky amines, unprotected se
- Li, Jianqing,Subramaniam, Krishnananthan,Smith, Daniel,Qiao, Jennifer X.,Li, Jie Jack,Qian-Cutrone, Jingfang,Kadow, John F.,Vite, Gregory D.,Chen, Bang-Chi
-
supporting information; experimental part
p. 214 - 217
(2012/02/16)
-
- N-(Pyridin-3-yl)benzamides as selective inhibitors of human aldosterone synthase (CYP11B2)
-
A series of 23 N-(Pyridin-3-yl)benzamides was synthesized and evaluated for their potential to inhibit human steroid-11β-hydroxylase (CYP11B1) and human aldosterone synthase (CYP11B2). The most potent and selective CYP11B2 inhibitors (IC50 valu
- Zimmer, Christina,Hafner, Marieke,Zender, Michael,Ammann, Dominic,Hartmann, Rolf W.,Vock, Carsten A.
-
supporting information; experimental part
p. 186 - 190
(2011/02/25)
-
- Use of molecular oxygen as a reoxidant in the synthesis of 2-substituted benzothiazoles via palladium-catalyzed C-H functionalization/intramolecular C-S bond formation
-
Molecular oxygen (O2) was successfully employed as a reoxidant in cyclizations of thiobenzanilides 1a-s through a palladium-catalyzed C-H functionalization/intramolecular C-S bond formation process, leading to an efficient, green method for the synthesis of 2-arylbenzothiazoles 2a-s. Addition of cesium fluoride (CsF) greatly enhanced the reactions, which produced variously substituted 2-arylbenzothiazoles with good functional group tolerance. Thioureas 4a-j were also found to be suitable substrates for the cyclization process using a palladium/O2 catalyst system, thus generating 2-aminobenzothiazoles 5a-j. One-pot syntheses of 2-aminobenzothiazoles 5a-j from aryl isothiocyanates 6 and amines 7 were also successful.
- Inamoto, Kiyofumi,Hasegawa, Chisa,Kawasaki, Junpei,Hiroya, Kou,Doi, Takayuki
-
experimental part
p. 2643 - 2655
(2010/12/25)
-
- Copper-catalyzed synthesis of benzoxazoles via a regioselective C-H functionalization/C-O bond formation under an air atmosphere
-
(Chemical Equation Presented) An efficient method for the synthesis of functionalized benzoxazoles is described that involves a copper(II)-catalyzed regioselective C-H functionalization/C-O bond formation protocol. The use of dichlorobenzene as a solvent at 160°C allows the use of air as the terminal oxidant in the catalytic synthesis of benzoxazoles in a process that has high functional group tolerance. The presence of a directing group at the meta position markedly improves the reaction efficacy and a variety of 7-substituted benzoxazoles are selectively produced under mild reaction conditions. The mechanism of the reaction is also discussed in this report.
- Ueda, Satoshi,Nagasawa, Hideko
-
supporting information; experimental part
p. 4272 - 4277
(2009/09/08)
-
- Lewis acid acceleration of C-N bond-forming reductive elimination from heteroarylpalladium complexes and catalytic amidation of heteroaryl bromides
-
A large acceleration of carbon-nitrogen bond-forming reductive elimination from heteroarylpalladium amido complexes by addition of Lewis acids is described. Several lines of data imply that this effect arises from coordination of the Lewis acid to the nitrogen of the heteroaryl group. The presence of this coordination was confirmed by isolation of a Lewis acid base complex with a borane coordinated to the pyridyl nitrogen. This adduct underwent reductive elimination faster than the complex lacking the Lewis acid, and it occurred in high yield. Control experiments showed that this acceleration of reductive elimination was not observed for the reactions of arylpalladium amide complexes. This effect of Lewis acids translated to catalytic C-N bond-forming coupling processes. The binding of Lewis acids to the pyridyl nitrogen led to an acceleration of the amidation of unactivated heteroaryl bromides catalyzed by palladium complexes of Xantphos. The rates were faster and the yields were higher for reactions of BEt3 adducts of basic heteroaryl bromides than for the free heteroaryl bromides. This phenomenon draws parallels to the beneficial effect of Lewis acids on the reductive elimination of nitriles from arylmetal cyanide complexes and the catalytic hydrocyanation of olefins. Copyright
- Shen, Qilong,Hartwig, John F.
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p. 7734 - 7735
(2008/02/07)
-
- Aminolysis of allyl esters with bislithium aryl amides
-
The aminolysis of allyl esters with bislithium amides is reported. Tertiary aryl amides were synthesized in a one-pot reaction with bislithium amides and a suitable electrophile in good yields. The scope of this reaction was demonstrated with a variety of anilines and aminopyridines and applied to the synthesis of triphenylmethylacetamides.
- Faler, Catherine A.,Joullié, Madeleine M.
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p. 7229 - 7231
(2007/10/03)
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- Behaviour of N-pyridylbenzamides versus benzanilides in the ortho-directed lithiation of masked aromatic carboxylic acids
-
The reaction of N-pyridylbenzamides 1-3 with n-butyllithium or sec-butyllithium has been examined. The perfect selectivity that has been observed until now in the lithiation of anilides, a reaction used for ortho-functionalisation of masked aromatic carboxylic acids, has been broken; our results indicate that the pyridine ring at the position ortho to the directed metallation group is more susceptible to lithiation than the homoaromatic ring itself. This was proved in an intermolecular comparative study of benz-, picolin- and isonicotinanilides 14-16, and N-cumylbenzamide (17). Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Jozwiak, Andrzej,Brzezinski, Jacek Z.,Plotka, Mieczyslaw W.,Szczesniak, Aleksandra K.,Malinowski, Zbigniew,Epsztajn, Jan
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p. 3254 - 3261
(2007/10/03)
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- Azabicyclic compounds, preparation thereof and use as medicines, in particular as antibacterial agents
-
The invention relates to new heterocyclic compounds of general formula (I), and their salts with a base or an acid: The invention also relates to a process for the preparation of these compounds as well as their use as medicaments, in particular as anti-bacterial agents.
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Page/Page column 16
(2010/11/30)
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- Photoreaction of 2-halo-N-pyridinylbenzamide: Intramolecular cyclization mechanism of phenyl radical assisted with n-complexation of chlorine radical
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The photochemical behavior of 2-halo-N-pyridinylbenzamide (1-4 in Chart 1) was studied. The photoreaction of 2-chloro-N-pyridinylbenzamides 1a, 2a, 3a, and 4 afforded photocyclized products, benzo[c]naphthyridinones (6-9 and 16), in high yield, whereas the bromo analogues 1b, 2b, and 3b produced extensively photoreduced products, N-pyridinylbenzamides (1c, 10, and 11), with minor photocyclized product. Since the photocyclization reaction of 2-chloro-N-pyridinylbenzamide is retarded by the presence of oxygen and sensitized by the presence of a triplet sensitizer, acetone or acetophenone, a triplet state of the chloro analogue is involved in the reaction. Since several radical intermediates, particularly n-complexes of chlorine radical, are identified in the laser flash photolysis of 2-chloro-N-pyridinylbenzamide, an intramolecular cyclization mechanism of phenyl radical assisted with n-complexation of chlorine radical for the cyclization reaction is proposed: the triplet state (78 kcal/mol) of the chloro analogue (1a), which is populated by the excitation of 1a undergoes a homolytic cleavage of the C-Cl bond to give phenyl and chlorine radicals; while chlorine radical holds the neighbor pyridinyl ring with its n-complexation, the intramolecular arylation of the phenyl radical with the pyridinyl ring proceeds to produce a conjugated 2,3-dihydropyridinyl radical and then the conjugated radical aromatizes to afford a cyclized product, benzo[c]naphthyridinone by ejecting a hydrogen. The photoreduction product can be formed by hydrogen atom abstraction of the phenyl a radical from the environment.
- Park,Jung,Kim,Kim,Song,Kim
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p. 2197 - 2206
(2007/10/03)
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- Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy
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The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core awl ring resulted in inhibitors of equator less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor- derived cell line.
- O'Connor, Stephen J.,Barr, Kenneth J.,Wang, Le,Sorensen, Bryan K.,Tasker, Andrew S.,Sham, Hing,Shi-Chung, Ng,Cohen, Jerome,Devine, Edward,Cherian, Sajeev,Saeed, Badr,Zhang, Haichao,Jang Yun, Lee,Warner, Robert,Tahir, Stephen,Kovar, Peter,Ewing, Patricia,Alder, Jeffrey,Mitten, Michael,Leal, Juan,Marsh, Kennan,Bauch, Joy,Hoffman, Daniel J.,Sebti, Said M.,Rosenberg, Saul H.
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p. 3701 - 3710
(2007/10/03)
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- Intramolecular hydrogen bonding in acylated 2,2'-bipyridine-3,3'-diamines
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Various di- and monoacylated 2,2'-bipyridine-3,3'-diamines (amides 1a-f, 8, 9, ureas 1g-h, 8b and acylureas 1i-j) have been synthesized and characterized.All molecules show strong intramolecular hydrogen bonding between the acyl NH of one ring and the pyr
- Palmans, A. R. A.,Vekemans, J. A. J. M.,Meijer, E. W.
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p. 277 - 284
(2007/10/02)
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- Non-acidic anti-inflammatory compounds: activity of N-(4,6-dimethyl-2-pyridinyl) benzamides and derivatives
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The inhibition of the carragenin-induced rat-paw edema by previously synthesized N-(4,6-dimethyl)-2-pyridinyl) benzamides was evaluated.Amoung the 29 tested compounds, secondary benzamides 1, 12 and tertiary benzamide 60 exhibited a significant anti-inflammatory activity.It prompted us to envision a pharmacomodulation in this series by structural modifications on the homocycle, the amide function and the heterocycle.Although benzamide 38, acetamide 50 and benzylamine 56 elicited marked inhibitory activity, none was more active than N-(4,6-dimethyl-2-pyridinyl) benzamide 1. The mechanism of the anti-inflammatory action of 1 was investigated.The results showed that this molecule reduced eicosanoid biosynthesis but was unable to reduce cyclooxygenase or lipoxygenase activities.Although it did not directly block phospholipase activity, however, an inhibitory process at this level is likely.
- Robert-Piessard, Sylvie,Le Baut, Guillaume,Courant, Jacqueline,Brion, Jean-Daniel,Sparfel, Louis,et al.
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- 1H AND 13C NMR STUDY OF PYRIDYLAMIDES AND THIONAMIDES
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1H and 13C NMR spectra are reported for several pyridylamides and thionamides.Complete analyses of the 13C spectra have yielded the chemical shifts and the direct and long range (13C, 1H) coupling constants. 13C chemical shifts show linear relationship with charge densities computed by CNDO method.The variations in the chemical shifts are discussed.
- Sudha, L. V.,Manogaran, S.,Sathyanarayana, D. N.
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p. 137 - 144
(2007/10/02)
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- INVESTIGATION OF NITROGEN- AND SULFUR-CONTAINING HETEROCYCLES. 38. REACTIONS OF 2-MERCAPTO-3-UREIDOPYRIDINES WITH HALO β-DIKETONES
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The reaction of 2-mercapto-3-ureido-6-chloropyridine with chlorodibenzoylmethane in the presence of alkali leads to 2-(benzoylmethylthio)-3-benzamido-6-chloropyridine, whereas the reaction in the absence of alkali leads to 2-chloro-6-phenyl-7-benzoylpyrid
- Traven', N. I.,Safonova, T. S.
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p. 607 - 611
(2007/10/02)
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