- Palladium/copper-catalyzed aerobic oxidative C-H carbonylation for the synthesis of o-aminobenzoates
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The palladium/copper-catalyzed aerobic oxidative C-H carbonylation for the synthesis of o-aminobenzoates is described. Molecular oxygen is used as the terminal oxidant. This methodology proceeds with a wide range of N-substituted anilines and alcohols and gives straightforward access to valuable o-aminobenzoates.
- Li, Wu,Duan, Zhengli,Jiang, Ru,Lei, Aiwen
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- A novel pathway for the thermolysis of N-nitrosoanthranilates using flash vacuum pyrolysis leading to 7-aminophthalides
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Flash vacuum pyrolysis of methyl N-methyl-N-nitrosoanthranilate leads to elimination of nitric oxide and disproportionation of the formed N-radical to 7-(methylamino)phthalide and methyl N-methylanthranilate. This transformation was found to be a convenient, solvent-free method for the preparation of 7-(methylamino)phthalides. An alternative route through pyrolysis of N-benzyl-N-methyl anthranilates was also investigated. This journal is
- Dallinger, Doris,Kappe, C. Oliver,Zlatkovi?, Dragan
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supporting information
p. 8371 - 8375
(2020/11/05)
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- Palladium-Catalyzed Multistep Tandem Carbonylation/N-Dealkylation/Carbonylation Reaction: Access to Isatoic Anhydrides
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A novel and efficient synthesis of isatoic anhydride derivatives was developed via palladium-catalyzed multistep tandem carbonylation/N-dealkylation/carbonylation reaction with alkyl as the leaving group and tertiary anilines as nitrogen nucleophiles. This approach features good functional group compatibility and readily available starting materials. Furthermore, it provided a convenient approach for the synthesis of biologically and medicinally useful evodiamine.
- Wang, Shoucai,Li, Xuan,Zang, Jiawang,Liu, Meichen,Zhang, Siyu,Jiang, Guangbin,Ji, Fanghua
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p. 2672 - 2679
(2020/02/04)
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- One-Pot Total Synthesis of Evodiamine and Its Analogues through a Continuous Biscyclization Reaction
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The one-pot total synthesis of evodiamine and its analogues is achieved using a three-component reaction. Through continuous biscyclization, various readily available substrates with good functional group tolerance were easily incorporated into biologically active quinazolinocarboline backbones. The use of triethoxymethane as a cosolvent was crucial for this quick and straightforward transformation.
- Wang, Zi-Xuan,Xiang, Jia-Chen,Wang, Miao,Ma, Jin-Tian,Wu, Yan-Dong,Wu, An-Xin
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p. 6380 - 6383
(2018/10/20)
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- Acetic Acid Accelerated Visible-Light Photoredox Catalyzed N-Demethylation of N,N-Dimethylaminophenyl Derivatives
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N,N-Dimethylaminophenyl moiety is a common fragment in medicinal chemistry as several pharmaceuticals bearing this privileged motif are on the market and under clinical evaluation. Oxidative N-demethylation is generally regarded as the major metabolic pathway. However, pharmacokinetics, metabolites studies as well as the further structural modification are precluded by the impracticality of chemical synthesis. Here we report that acetic acid can significantly accelerate visible-light photoredox catalyzed N-demethylation of N,N-dimethylaminophenyl derivatives. This approach is easy for large scale reaction and even for potential industrial manufacture. (Figure presented.).
- Wu, Guolin,Li, Yazhen,Yu, Xuemei,Gao, Yu,Chen, Haijun
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supporting information
p. 687 - 692
(2017/02/23)
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- Chemoselective Schwartz Reagent Mediated Reduction of Isocyanates to Formamides
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Addition of the in situ generated Schwartz reagent to widely available isocyanates constitutes a chemoselective, high-yielding, and versatile approach to the synthesis of variously functionalized formamides. Steric and electronic factors or the presence of sensitive functionalities (esters, nitro groups, nitriles, alkenes) do not compromise the potential of the method. Full preservation of the stereochemical information contained in the starting materials is observed. The use of formamides in the nucleophilic addition of organometallic reagents (Chida-Sato allylation, Charette-Huang addition to imidoyl triflate activated amides, Matteson homologation of boronic esters) is briefly investigated.
- Pace, Vittorio,De La Vega-Hernández, Karen,Urban, Ernst,Langer, Thierry
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supporting information
p. 2750 - 2753
(2016/06/15)
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- Palladium-catalyzed oxidative carbonylation of aromatic C-H bonds of N -alkylanilines with CO and alcohols for the synthesis of o -aminobenzoates
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A Pd(II)-catalyzed C-H monocarbonylation of N-alkylanilines for the synthesis of o-aminobenzoates has been developed. Various aliphatic alcohols and phenol were tolerated in the reaction to afford the corresponding o-aminobenzoates in good yields under mild balloon pressure of CO.
- Chen, Ming,Ren, Zhi-Hui,Wang, Yao-Yu,Guan, Zheng-Hui
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p. 1258 - 1263
(2015/01/30)
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- Optimisation of LRRK2 inhibitors and assessment of functional efficacy in cell-based models of neuroinflammation
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LRRK2IN1 is a highly potent inhibitor of leucine-rich repeat kinase 2 (LRRK2, IC50 = 7.9 nM), an established target for treatment of Parkinson's disease. Two LRRK2IN1 analogues 1 and 2 were synthesised which retained LRRK2 inhibitory activity (1: IC50 = 72 nM; 2: IC50 = 51 nM), were predicted to have improved bioavailability and were efficacious in cell-based models of neuroinflammation. Analogue 1 inhibited IL-6 secretion from LPS-stimulated primary human microglia with EC50 = 4.26 μM. In order to further optimize the molecular properties of LRRK2IN1, a library of truncated analogues was designed based on docking studies. Despite lacking LRRK2 inhibitory activity, these compounds show antineuroinflammatory efficacy at micromolar concentration. The compounds developed were valuable tools in establishing a cell-based assay for assessing anti-neuroinflammatory efficacy of LRRK2 inhibitors. Herein, we present data that IL-1β stimulated U87 glioma cell line is a reliable model for neuroinflammation, as data obtained in this model were consistent with results obtained using primary human microglia and astrocytes.
- Munoz, Lenka,Kavanagh, Madeline E.,Phoa, Athena F.,Heng, Benjamin,Dzamko, Nicolas,Chen, Ew-Jun,Doddareddy, Munikumar Reddy,Guillemin, Gilles J.,Kassiou, Michael
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- Palladium-catalyzed regioselective carbonylation of C-H bonds of N -alkyl anilines for synthesis of isatoic anhydrides
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A Pd-catalyzed regioselective C-H bond carbonylation of N-alkyl anilines for the synthesis of isatoic anhydrides has been developed. The key Pd-catalyst intermediate has been isolated and characterized. This novel Pd-catalyzed carbonylation reaction tolerates a wide range of functional groups and is a reliable method for the rapid elaboration of readily available N-alkyl anilines into a variety of substituted isatoic anhydrides under mild conditions.
- Guan, Zheng-Hui,Chen, Ming,Ren, Zhi-Hui
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p. 17490 - 17493,4
(2020/09/16)
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- Anthranilic acid-based inhibitors of phosphodiesterase: Design, synthesis, and bioactive evaluation
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Our previous studies identified two 2-benzoylaminobenzoate derivatives 1, which potently inhibited superoxide (O2-) generation induced by formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) in human neutrophils. In an attempt to improve their activities, a series of anthranilic acid derivatives were synthesized and their anti-inflammatory effects and underlying mechanisms were investigated in human neutrophils. Of these, compounds 17, 18, 46, 49, and 50 showed the most potent inhibitory effect on FMLP-induced release of O2- in human neutrophils with IC50 values of 0.20, 0.16, 0.15, 0.06, and 0.29 μM, respectively. SAR analysis showed that the activities of most compounds were dependent on the ester chain length in the A ring. Conversely, a change in the linker between the A and B ring from amide to sulfonamide or N-methyl amide, as well as exchanges in the benzene rings (A or B rings) by isosteric replacements were unfavorable. Further studies indicated that inhibition of O2- production in human neutrophils by these anthranilic acids was associated with an elevation in cellular cAMP levels through the selective inhibition of phosphodiesterase 4. Compound 49 could be approved as a lead for the development of new drugs in the treatment of neutrophilic inflammatory diseases.
- Cheng, Yih-Dih,Hwang, Tsong-Long,Wang, Han-Hsiang,Pan, Tai-Long,Wu, Chin-Chung,Chang, Wen-Yi,Liu, Yi-Ting,Chu, Tzu-Chi,Hsieh, Pei-Wen
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experimental part
p. 7113 - 7125
(2011/11/04)
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- Alkylidenephosphoranes in heterocyclic synthesis: Reactivity of benzoxazinones with resonance-stabilized phosphorus ylides
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2H-3,1-Benzoxazine-2,4(1H)-dione and its N-methyl analogue react with alkylidenephosphoranes to give substituted quinolines and benzazepines as well as indanone and furan derivatives. Reaction mechanisms to explain the formation of products obtained are outlined. Georg Thieme Verlag Stuttgart.
- Kamel, Azza A.,Abdou, Wafaa M.
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p. 1269 - 1273
(2007/12/27)
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- Mono-N-methylation of functionalized anilines with alkyl methyl carbonates over NaY faujasites. 4. Kinetics and selectivity
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(Chemical Equation Presented) In the presence of NaY faujasite as the catalyst, the reaction of bifunctional anilines (1-4: XC6H 4-NH2; X = OH, CO2H, CH2OH, and CONH2) with methyl alkyl carbonates [MeOCO2R′: R′ = Me or MeO(CH2)2O(CH2)2] proceeds with a very high mono-N-methyl selectivity (XC6H 4NHMe up to 99%), and chemoselectivity as well, with other nucleophilic functions (OH, CO2H, CH2OH, CONH2) fully preserved from alkylation and/or transesterification reactions. Aromatic substituents, however, modify the relative reactivity of amines 1-4: good evidence suggests that, not only steric and electronic effects, but, importantly, direct acid-base interactions between substituents and the catalyst are involved. Weakly acidic groups (OH, CH2OH, CONH2, pKa ≥ 10) may help the reaction, while aminobenzoic acids (pK a of 4-5) are the least reactive substrates. The solvent polarity also affects the reaction, which is faster in xylene than in the more polar diglyme. The mono-N-methyl selectivity is explained by the adsorption pattern of reagents within the zeolite pores: a BAl2 displacement of the amine on methyl alkyl carbonate should occur aided by the geometric features of the NaY supercavities. Different factors account for the reaction chemoselectivity. Evidence proves that the polarizability of the two nucleophilic terms (NH 2 and X groups) of anilines is relevant, although adsorption and confinement phenomena of reagents promoted by the zeolite should also be considered.
- Selva, Maurizio,Tundo, Pietro,Foccardi, Tommaso
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p. 2476 - 2485
(2007/10/03)
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- A novel intramolecular photocyclization of N-(2-bromoalkanoyl) derivatives of 2-acylanilines via 1,8-hydrogen abstraction
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The photochemical reactions of different N-(2-acylphenyl)-2-bromo-2- methylpropanamides have been investigated. Irradiation of the N-unsubstituted anilides 1a-1c gave the corresponding dehydrobromination, cyclization, and bromo-migration products 2, 3, and 4, respectively (Table 1). Irradiation of the N-alkyl anilides 1e-1g afforded the corresponding deacylation and cyclization products 5 and 6, respectively, whereas irradiation of the N-alkyl anilides 1i-1k, carrying 2-benzoyl groups on the aromatic rings, afforded the unexpected tricyclic lactams 7 (besides 2, 5, and 6). The formation of the cyclization products 6 could be rationalized in terms of an electrocyclic ring closure of the 6π-electron-conjugated enamides 2 produced by dehydrobromination of 1, followed by thermal 1,5-acyl migration (Path B in the Scheme). The formation of the bridged lactams 7 probably follows a mechanism involving the 1,7-diradical 8 generated by ζ-H-abstraction (1.8-H transfer) by an excited acyl O-atom (Path A).
- Nishio, Takehiko,Koyama, Hiroyuki,Sasaki, Daigo,Sakamoto, Masami
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p. 996 - 1003
(2007/10/03)
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- Reaction of functionalized anilines with dimethyl carbonate over NaY faujasite. 3. Chemoselectivity toward mono-N-methylation
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In the presence of NaY faujasite, dimethyl carbonate (MeOCO2Me, DMC) is a highly chemoselective methylating agent of functionalized anilines such as aminophenols (1), aminobenzyl alcohols (2), aminobenzoic acids (3), and aminobenzamides (4). The reaction proceeds with the exclusive formation of N-methylanilines without any concurrent O-methylation or N-/O-methoxy carbonylation side processes. Particularly, only mono-N-methyl derivatives [XC6H4NHMe, X = o-, m-, and p-OH; o- and p-CH 2OH; o- and P-CO2H; o- and p-CONH2] are obtained with selectivity up to 99% and isolated yields of 74-99%. DMC, which usually promotes methylations only at T > 120 °C, is activated by the zeolite catalyst and it reacts with compounds 1, 2, and 4, at 90 °C. Aminobenzoic acids (3) require a higher reaction temperature (≥130 °C).
- Selva, Maurizio,Tundo, Pietro,Perosa, Alvise
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p. 7374 - 7378
(2007/10/03)
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- Use of N-lithiated ethyl anthranilates as 1,4-dipole equivalents in 1,4-dipole-aryne cycloaddition: a novel approach to the synthesis of acridones
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A new strategy for acridones based on 1,4-dipolar cycloaddition of N-lithiated ethyl anthranilates, which function as 1,4-dipole equivalents, with arynes is reported.
- Khanapure,Bhawal,Biehl
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p. 2869 - 2972
(2007/10/02)
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- Reduction et photoreduction de derives de l'acide carbonique influence de l'hexamethylphosphorotriamide
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Photoreduction and reduction of carbonic acid derivatives in HMPT have been compared.The highest yield of alkane was obtained from N,N-dimethylthiocarbamates either by the photochemical method or by reduction with a dissolved metal.Competitive reactions have been characterized: - during the photoreduction not only the alkane but products of a photo-Fries rearrangement and products of a homolytic cleavage were detected; - basic reactions can compete with the reduction of carbonic acid derivatives by sodium in HMPT.
- Dembele, Albert,Deshayes, Henri,Pete, Jean-Pierre
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p. 671 - 680
(2007/10/02)
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- 2,1-Benzisothiazoles. XIII . Intermediates and Products in the Sulfur Extrusion Reaction of 2,1-Benzisothiazolines-3(1H)-one. A New Synthesis of 11H-Pyridoquinazolin-11-one ("Pyracridone")
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Triethyl phosphite abstracts sulfur from 2,1-benzisothiazolin-3(1H)-one (1); a reaction intermediate is the spirocyclic compound 11, and products include the benzoxazine 6 and polyanthraniloyl compounds.In the presence of pyridine, pyracridone (13) is formed.The ketene-imine 9 is probably not an intermediate in these reactions.The reactions of other nucleophiles with 1 and with its N-methyl derivative 15, have been examined.
- Davis, Michael,Hook, Robert J.,Wu, Wen Yang
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p. 369 - 373
(2007/10/02)
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