- Computational and Synthetic approach with Biological Evaluation of Substituted Quinoline derivatives as small molecule L858R/T790M/C797S triple mutant EGFR inhibitors targeting resistance in Non-Small Cell Lung Cancer (NSCLC)
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New substituted quinoline derivatives were designed and synthesized via a five-step modified Suzuki coupling reaction. A comparative molecular docking study was carried out on two different types of EGFR enzymes which include wild-type (PDB: 4I23) and T790M mutated (PDB: 2JIV) respectively. Compounds were also validated upon T790M/C797S mutated (PDB ID: 5D41) EGFR enzyme at the allosteric binding site. All docking studies confirmed high potency and flexibility towards wild type as well as a mutated enzyme. Anticancer activity of the synthesized derivatives was examined against HCC827, H1975 (L858R/T790M/C797S and L858R/T790M), A549, and HT-29 cell lines by standard MTT assay. Most of the quinoline derivatives revealed a significant cytotoxic effect. The IC50 values of 4-(4-methylquinolin-2-yl)phenyl 4-(chloromethyl)benzoate (5j) were found to be 0.0042 μM, 0.02 μM, 1.91 μM, 3.82 μM and 3.67 μM while IC50 values of osimertinib were 0.0040 μM, 0.02 μM, ND, 0.99 μM and 1.22 μM, respectively. Compound 5j has shown excellent inhibitory activities against EGFR kinases triple mutant with IC 50 value 1.91 μM. It was observed that, compared to H1975, A549 and A431 cell lines, synthesized compounds significantly inhibited proliferation of the HCC827 cell line. These data suggested that synthesized compounds showed promising selective anticancer activity against tumor cells harboring EGFR Del E746-A750. The potency of compound 5j was compared through molecular dynamic simulations and an insilico ADMET study. QSAR models were generated and the best model was correctly compared with respect to predicted and observed activity of compounds. The built model will assist to design, refine and construct novel substituted quinoline derivatives as potent EGFR inhibitors in near future.
- Karnik, Kshipra S.,Sarkate, Aniket P.,Tiwari, Shailee V.,Azad, Rajaram,Burra, Prasad V.L.S.,Wakte, Pravin S.
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- Free energy perturbation guided Synthesis with Biological Evaluation of Substituted Quinoline derivatives as small molecule L858R/T790M/C797S mutant EGFR inhibitors targeting resistance in Non-Small Cell Lung Cancer (NSCLC)
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Two different schemes of novel substituted quinoline derivatives were designed and synthesized via simple reaction steps and conditions. A comparative molecular docking study was carried out on two different types of EGFR enzymes which include wild-type (PDB: 4I23) and T790M mutated (PDB: 2JIV) respectively. Compounds were also validated upon T790M/C797S mutated (PDB ID: 5D41) EGFR enzyme at the allosteric binding site. Free energy perturbations were carried out to determine the absolute binding free energy of a protein–ligand complex in the form of ΔGbinding, which in turn provided 4ab and 5ad as the most potential contenders through the structural enhancement in the determined initial scaffolds. Anticancer activity of the synthesized derivatives was examined against HCC827, H1975 (L858R/T790M), A549, and HT-29 cell lines by standard MTT assay. Compound 4ad (6-chloro-2-(isoindolin-2-yl)-4-methylquinoline) has shown excellent inhibitory activities against mutant EGFR kinase with IC50 value 0.91 μM. The potency of compounds 4ab, 4ad and 5ad was compared through an insilico ADMET study.
- Azad, Rajaram,Karnik, Kshipra S.,Sarkate, Aniket P.,Tiwari, Shailee V.,Wakte, Pravin S.
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- 1,4,2-Dioxazol-5-ones as Isocyanate Equivalents: An Efficient Synthesis of 2-Quinolinones via β-Keto Amides
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Under thermal conditions, 1,4,2-dioxazol-5-ones are known to undergo decarboxylation followed by Lossen's rearrangement to yield isocyanates. Described herein is the in situ trapping of the resulting isocyanates with carbon nucleophiles to synthesize β-keto amides. Furthermore, a general and mild method for the conversion of the resulting β-keto amides into quinolin-2-ones is reported.
- Vala, Anand,Parmar, Nirali,Soni, Jigar Y.,Kotturi, Sharadsrikar,Guduru, Ramakrishna
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supporting information
p. 2080 - 2084
(2021/10/07)
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- Palladium catalysed hydrolysis-free arylation of aliphatic nitriles for the synthesis of 4-arylquinolin-2-one/pyrazolone derivatives
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Palladium catalysed addition of arylboronic acid to the readily available 2-cyano-(N-aryl)-acetamide or ethyl-2-cyanoacetate followed by subsequent reaction transform them into the biologically significant 4-arylquinolin-2-one or pyrazolone derivatives. The reaction conditions are robust enough to prevent the hydrolysis of ester/amide moiety during arylation. In addition, the unactivated nitrile moiety in the acetonitrile also converted to the corresponding acetophenone derivative.
- Krishna Reddy, Singarajanahalli Mundarinti,Prasanna Kumari, Subramaniyan,Selva Ganesan, Subramaniapillai
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- Ru-NHC-Catalyzed Asymmetric Hydrogenation of 2-Quinolones to Chiral 3,4-Dihydro-2-Quinolones
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Direct enantioselective hydrogenation of unsaturated compounds to generate chiral three-dimensional motifs is one of the most straightforward and important approaches in synthetic chemistry. We realized the Ru(II)-NHC-catalyzed asymmetric hydrogenation of 2-quinolones under mild reaction conditions. Alkyl-, aryl- and halogen-substituted optically active dihydro-2-quinolones were obtained in high yields with moderate to excellent enantioselectivities. The reaction provides an efficient and atom-economic pathway to construct simple chiral 3,4-dihydro-2-quinolones. The desired products could be further reduced to tetrahydroquinolines and octahydroquinolones.
- Daniliuc, Constantin,Glorius, Frank,Hu, Tianjiao,Lückemeier, Lukas
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supporting information
p. 23193 - 23196
(2021/09/25)
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- Metal-Free C-H [5 + 1] Carbonylation of 2-Alkenyl/Pyrrolylanilines Using Dioxazolones as Carbonylating Reagents
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A novel metal-free C-H [5 + 1] carbonylative annulation of 2-alkenyl/pyrrolylanilines with dioxazolones has been established for the assembly of the privileged quinolinones and pyrrolyl-fused quinoxalinones. Entirely differing from the existing reports, the dioxazolones herein behave with an innovative chemistry and first emerge as carbonylating reagents to participate in annulation reactions. Moreover, this process features exceedingly simple operation (only solvent) and tolerates both vinyl and aryl substrates. Comprehensive mechanistic studies indicate that the formed isocyanate intermediate plays a crucial role in enabling the carbonylation annulation.
- Nan, Jiang,Chen, Pu,Gong, Xue,Hu, Yan,Ma, Qiong,Wang, Bo,Ma, Yangmin
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supporting information
p. 3761 - 3766
(2021/05/10)
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- Anti-Hydroarylation of Activated Internal Alkynes: Merging Pd and Energy Transfer Catalysis
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A general catalytic anti-hydroarylation of electron-deficient internal alkynes compatible with both electron-poor and electron-rich aryl reagents is reported. This selectivity is achieved through a sequential syn-carbopalladation of the alkyne by an Ar-Pd species, followed by a tandem, Ir-photocatalyzed, counter-thermodynamic E → Z isomerization. The use of ortho-substituted boronic acids enables direct access to pharmaceutically relevant heterocyclic cores via a cascade process. Mechanistic insight into the involvement of Ar-Pd versus Pd-H as an active species is provided.
- Carretero, Juan C.,Corpas, Javier,Gómez Arrayás, Ramón,Mauleón, Pablo
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- Lactamization of alkenyl C-H bonds to generate 2-quinolinones with triphosgene
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A simple and easy-going method is developed to synthesize the analogues of 2-quinolinones by using triphosgene (BTC) as the carbonyl source. In these reactions, both the toxic carbon monoxide (CO) and phosgene are avoided and the 2-quinolinones are obtained in moderate to good yields under mild conditions, all of which are anticipated to be meaningful in both industry and laboratory.
- Du, Guizhi,Wang, Zixiao,Zhang, Zhen
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p. 600 - 608
(2020/06/03)
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- Palladium Catalyzed Direct Acylation of Iodo-Acetanilides/Iodo-Phenyl Acetates: Domino One-Pot Synthesis of 2-Quinolinones
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Pd-catalyzed direct acylation reaction of iodoacetanilides/iodophenyl acetates with aldehydes is presented. Simple, bench-top aldehydes were used as non-toxic acylating agents. This protocol comprises direct coupling with aldehydes without activating the carbonyl group and without directing group assistance. The strategy was applied to a domino one-pot synthesis of 2-quinolinones through acylation and intramolecular aldol condensation. Significantly, the strategy was extended to the domino one-pot synthesis of drugs and bioactive compounds.
- Basuli, Scuhand,Satyanarayana, Gedu
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p. 957 - 970
(2017/12/07)
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- Synthesis of 2-Quinolinones via a Hypervalent Iodine(III)-Mediated Intramolecular Decarboxylative Heck-Type Reaction at Room Temperature
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A hypervalent iodine(III)-mediated intramolecular decarboxylative Heck-type reaction of 2-vinyl-phenyl oxamic acids has been developed. The unique ring-strain-enabled radical decarboxylation mechanism is preliminarily revealed. This protocol features metal-free reaction conditions and operational simplicity, allowing the lactamization of 2-vinylanilines using a readily accessible carbonyl source and the synthesis of various 2-quinolinones with excellent chemoselectivity at room temperature.
- Fan, Huaqiang,Pan, Peng,Zhang, Yongqiang,Wang, Wei
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p. 7929 - 7932
(2019/01/04)
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- Transition-Metal-Free Synthesis of Acridones via Base-Mediated Intramolecular Oxidative C?H Amination
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Intramolecular oxidative C?H amination of 2-aminobenzophenones was achieved in the presence of potassium tert-butoxide and dimethyl sulfoxide. A series of functionalized acridones were prepared in moderate to excellent yields in a mild, efficient, and transition-metal-free manner. (Figure presented.).
- Wei, Wen-Tao,Sheng, Jian-Fei,Miao, Hui,Luo, Xiang,Song, Xian-Heng,Yan, Ming,Zou, Yong
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p. 2101 - 2106
(2018/06/14)
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- Palladium-Catalyzed Ullmann Cross-Coupling of β-Iodoenones and β-Iodoacrylates with o-Halonitroarenes or o-Iodobenzonitriles and Reductive Cyclization of the Resulting Products to Give Diverse Heterocyclic Systems
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The palladium-catalyzed Ullmann cross-coupling of β-iodoenones and β-iodoacrylates such as 5 (X = I) with o-halonitroarenes and o-iodobenzonitriles including 2 affords products such as compound 7. These can be engaged in a range of reductive cyclization r
- Khan, Faiyaz,Dlugosch, Michael,Liu, Xin,Khan, Marium,Banwell, Martin G.,Ward, Jas S.,Carr, Paul D.
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p. 2770 - 2773
(2018/05/22)
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- Palladium-catalyzed arylation/cyclization/desulfonation cascades toward 4-aryl quinolin-2(1H)-ones with diaryliodonium salts
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Palladium-catalyzed cascades of arylation/cyclization/desulfonation of ortho-aminocinnamate esters by using diaryliodonium salts afforded a wide range of 4-aryl quinolin-2(1H)-ones. As such, the desired 4-aryl quinolin-2(1H)-ones with potential biological activity has been synthesized in the yields of 34–96%.
- Han, Jianwei,Wu, Xunshen,Zhang, Zhiang,Wang, Limin
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supporting information
p. 3433 - 3436
(2017/08/08)
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- Method for preparing 4-aryl-2-quinolinone through carbon dioxide
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The invention discloses a method for preparing 4-aryl-2-quinolinone through carbon dioxide, and belongs to the technical field of carbon dioxide comprehensive utilization. The method comprises the following concrete process steps: in a dehydrated and deox
- -
-
Paragraph 0023; 0024; 0026
(2017/04/03)
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- A Facile Synthesis of 5-Phenyl-Dibenzo[b, g][1,8]Napthyridines
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The Vilsmeier Haack heterocyclization of 2-aryl amino-4-phenyl quinolines quinoline yielded the hitherto unknown 5-phenyl-dibenzo[b,g][1,8]naphthyridines in quantitative yield. The synthesis of aryl amines was achieved by the action of anilines on 2-chloro-4-phenyl quinoline, which in turn was sourced through the combes reaction of benzoyl acetanilides.
- Sampathkumar, Natarajan,Murugesh, Arumugam,Rajendran, Subramaniam Parameswaran
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p. 924 - 928
(2016/05/19)
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- Palladium-Catalyzed Multi-Component Reactions of N-Tosylhydrazones, 2-Iodoanilines and CO2towards 4-Aryl-2-Quinolinones
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A palladium-catalyzed three-component reaction between N-tosylhydrazones, 2-iodoanilines and atmospheric pressure CO2was developed whereby a tandem carbene migration insertion/lactamization strategy afforded 4-aryl-2-quinolinones in moderate to good yields. Notably, a wide range of functional groups were tolerated in this procedure. This protocol features the simultaneous formation of four novel bonds; two C?C, one C=C and one C?N (amide), representing an efficient methodology for incorporation of CO2into heterocycles.
- Sun, Song,Hu, Wei-Ming,Gu, Ning,Cheng, Jiang
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supporting information
p. 18729 - 18732
(2016/12/26)
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- Reactions of N,3-diarylpropiolamides with arenes under superelectrophilic activation: Synthesis of 4,4-diaryl-3,4-dihydroquinolin-2(1H)-ones and their derivatives
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The reaction of 3-aryl-N-(aryl)propiolamides with arenes in TfOH at room temperature for 0.5 h led to 4,4-diaryl-3,4-dihydroquinolin-2-(1H)-ones in yields of 44-98%. The obtained dihydroquinolinones were further transformed into the corresponding N-acyl or N-formyl derivatives. For the latter, the superelectrophilic activation of the N-formyl group by TfOH in the reaction with benzene resulted in the formation of N-(diphenylmethyl)-substituted dihydroquinolinones.
- Gurskaya, Larisa Yu.,Belyanskaya, Diana S.,Ryabukhin, Dmitry S.,Nilov, Denis I.,Boyarskaya, Irina A.,Vasilyev, Aleksander V.
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supporting information
p. 950 - 956
(2016/07/06)
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- Beyond a Protecting Reagent: DMAP-Catalyzed Cyclization of Boc-Anhydride with 2-Alkenylanilines
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A novel rapid synthesis of quinolines from 2-alkenylanilines has been described; the reaction involves an unexpected DMAP-catalyzed cyclization of 2-alkenylanilines with di-tert-butyl dicarbonate (Boc2O, 2.0 equiv), and a series of tert-butyl quinolin-2-yl carbonate with various functional groups have been synthesized in good yields under mild conditions. Furthermore, the tert-butyl quinolin-2-yl carbonate can be easily converted into corresponding quinolinones and 2-(pseudo)haloquinolines.
- Huang, Ya-Nan,Li, Yin-Long,Li, Jian,Deng, Jun
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p. 4645 - 4653
(2016/07/06)
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- Lactamization of sp2C?H Bonds with CO2: Transition-Metal-Free and Redox-Neutral
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The first direct use of carbon dioxide in the lactamization of alkenyl and heteroaryl C?H bonds to synthesize important 2-quinolinones and polyheterocycles in moderate to excellent yields is reported. Carbon dioxide, a nontoxic, inexpensive, and readily available greenhouse gas, acts as an ideal carbonyl source. Importantly, this transition-metal-free and redox-neutral process is eco-friendly and desirable for the pharmaceutical industry. Moreover, these reactions feature a broad substrate scope, good functional group tolerance, facile scalability, and easy product derivatization.
- Zhang, Zhen,Liao, Li-Li,Yan, Si-Shun,Wang, Lei,He, Yun-Qi,Ye, Jian-Heng,Li, Jing,Zhi, Yong-Gang,Yu, Da-Gang
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supporting information
p. 7068 - 7072
(2016/07/06)
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- Practical route to 2-quinolinones via a Pd-catalyzed C-H bond activation/C-C bond formation/cyclization cascade reaction
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Quinolinone derivatives were constructed via a Pd-catalyzed C-H bond activation/C-C bond formation/cyclization cascade process with simple anilines as the substrates. This finding provides a practical procedure for the synthesis of quinolinone-containing alkaloids and drug molecules. The utility of this method was demonstrated by a formal synthesis of Tipifarnib.
- Wu, Junliang,Xiang, Shaohua,Zeng, Jing,Leow, Minli,Liu, Xue-Wei
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supporting information
p. 222 - 225
(2015/01/30)
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- Ligand-enabled triple C-H activation reactions: One-pot synthesis of diverse 4-aryl-2-quinolinones from propionamides
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Diverse 4-aryl-2-quinolinones are prepared from propionamides in one pot by ligand-promoted triple sequential C-H activation reactions and a stereospecific Heck reaction. In these cascade reactions, three new C-C bonds and one C-N bond are formed to rapidly build molecular complexity from propionic acid. Building complexity: Diverse 4-aryl-2-quinolinones such as 1 are prepared from propionamides in one pot by pyridine ligand-promoted triple sequential C-H activation reactions and a stereospecific Heck reaction. In these cascade reactions, three new C-C bonds and one C-N bond are formed to rapidly build molecular complexity from propionic acid.
- Deng, Youqian,Gong, Wei,He, Jian,Yu, Jin-Quan
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supporting information
p. 6692 - 6695
(2014/07/08)
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- Alkyne hydroarylation with Au N-heterocyclic carbene catalysts
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Mono- and dinuclear gold complexes with N-heterocyclic carbene (NHC) ligands have been employed as catalysts in the intermolecular hydroarylation of alkynes with simple unfunctionalised arenes. Both mono- and dinuclear gold(III) complexes were able to catalyze the reaction; however, the best results were obtained with the mononuclear gold(I) complex IPrAuCl. This complex, activated with one equivalent of silver tetrafluoroborate, exhibited under acidic conditions at room temperature much higher catalytic activity and selectivity compared to more commonly employed palladium(II) catalysts. Moreover, the complex was active, albeit to a minor extent, even under neutral conditions, and exhibited lower activity but higher selectivity compared to the previously published complex AuCl(PPh3). Preliminary results on intramolecular hydroarylations using this catalytic system indicate, however, that alkyne hydration by traces of water may become a serious competing reaction.
- Tubaro, Cristina,Baron, Marco,Biffis, Andrea,Basato, Marino
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p. 246 - 253
(2013/03/28)
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- Synthesis of substituted coumarins and 2-quinolinones by cycloisomerisation of (hydroxy/aminophenyl)propargyl alcohols
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A new cycloisomerization strategy for the synthesis of coumarins and quinolinones is described. The addition of ethoxyacetylide to 2-hydroxyacetophenones directly resulted in 4-substituted coumarins by 6-endo-dig cycloisomerisation of the intermediate 3-ethoxy-1-(2-hydroxyphenyl)- 2-propyn-1-ols. Under similar conditions, 2-aminoacetophenone produced 2-ethoxyquinoline, a masked quinolinone, which was converted into the quinolinone by acid treatment. N-Protected intermediate 8 was isolated and converted into the quinolinone [with In(OTf)3 or H2SO 4] or the 3-iodo-2-quinolinone (with I2 and H +).
- Sridhar Reddy, Maddi,Thirupathi, Nuligonda,Babu, Madala Hari
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p. 5803 - 5809
(2012/11/07)
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- Reactions of N-phenylamide and phenyl (thio)esters of 3-phenylpropiolic acid with benzene under superelectrophilic activation
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N-Phenylamide and phenyl (thio)esters of 3-phenylpropiolic acid add benzene in the presence of CF3SO3H or AlX3 (X = Cl, Br) to give 4,4-diphenyl-3,4-dihydroquinolin-2-one, 4,4-diphenyl-3,4- dihydrocoumarin, and 4,4-dipheny
- Ryabukhin,Vasilyev,Vyazmin, S. Yu.
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p. 843 - 846
(2013/03/29)
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- Tandem-type Pd(ii)-catalyzed oxidative Heck reaction/intramolecular C-H amidation sequence: A novel route to 4-aryl-2-quinolinones
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A novel catalytic method for synthesizing 4-aryl-2-quinolinones is reported. The process involves two mechanistically independent, sequential Pd(ii)-catalyzed reactions - the oxidative Heck reaction and the intramolecular C-H amidation - both of which smoothly proceed in the presence of a single catalytic system in a one-pot manner. The Royal Society of Chemistry 2012.
- Inamoto, Kiyofumi,Kawasaki, Junpei,Hiroya, Kou,Kondo, Yoshinori,Doi, Takayuki
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p. 4332 - 4334
(2012/05/20)
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- 4-Aryl-2-quinolones from 3,3-diarylacrylamides through intramolecular copper-catalyzed C-H functionalization/C-N bond formation
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Free NH 3,3-diarylacrylamides are cyclized to substituted 2-quinolones in the presence of CuI, PPh3, and KO-t-Bu in o-xylene at 100 °C. The reaction proceeds through a C-H functionalization/C-N bond formation process. With unsymmetrical 3,3-diarylacrylamides, high selectivity is observed using substrates where the aromatic ring trans to the amide group bears o-methyl, -chloro, or -bromo substituents.
- Berrino, Roberta,Cacchi, Sandro,Fabrizi, Giancarlo,Goggiamani, Antonella
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p. 2537 - 2542
(2012/05/05)
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- Microwave-assisted facile synthesis of furo[3,2-b]indole derivatives via silver(I)-mediated [3+2] cycloaddition
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A robust one-pot process has been developed for the synthesis of a variety of furo[3,2-b]indoles from readily available o-propargylaminoacetophenones via silver(I)-mediated [3+2] cycloaddition. Copyright
- Zhang, Zhiguo,Fang, Shiliang,Liu, Qingfeng,Zhang, Guisheng
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supporting information; experimental part
p. 927 - 932
(2012/05/04)
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- An efficient synthesis of 4-arylquinolin-2(1 H)-ones and 3-alkenyl-4-arylquinolin-2(1 H)-one using a Pd/NiFe2O 4-catalyzed consecutive Heck reaction
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A convenient one-pot method for the synthesis of 4-arylquinolin-2(1H)-ones and 4-arylcoumarins has been described. The successive Heck reaction on substituted 2-iodoaniline and 2-iodophenol catalyzed by a Pd/nickel ferrite catalyst followed by in situ cyc
- Borhade, Sanjay R.,Waghmode, Suresh B.
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experimental part
p. 1355 - 1363
(2011/12/13)
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- Palladium-catalyzed intramolecular amidation of C(sp2)-H bonds: Synthesis of 4-aryl-2-quinolinones
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Figure presented A catalytic synthetic approach for the synthesis of 2-quinolinone compounds through a Pd-catalyzed C(sp2)-H functionalization/intramolecular amidation sequence is described. The cyclization process efficiently proceeds in the p
- Inamoto, Kiyofumi,Saito, Tadataka,Hiroya, Kou,Doi, Takayuki
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supporting information; experimental part
p. 3900 - 3903
(2010/07/05)
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- A general synthesis of quinolinones and benzothiazine 1,1-dioxides via ring closing metathesis
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A general synthesis of quinolinones and benzothiazine 1,1-dioxides is presented. A series of N-phenylacrylamides and N-phenylethylenesulfonamides were studied for their ability to undergo ring closing methathesis to yield the corresponding quinolinones and benzothiazine 1,1-dioxides, respectively. The reactions are general in scope and represents a mild method for the preparation of these heterocycles.
- Minville, Joannie,Poulin, Jason,Dufresne, Claude,Sturino, Claudio F.
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p. 3677 - 3681
(2008/09/20)
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- Knorr cyclizations and distonic superelectrophiles
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(Chemical Equation Presented) The acid-catalyzed Knorr cyclization has been studied by experimental and theoretical methods. The results of these studies indicate that β-ketoamides such as acetoacetanilide undergo diprotonation at the two carbonyl oxygen atoms to form distonic superelectrophiles. Direct observation of a dicationic superelectrophile was achieved by low-temperature 1H, 15N, and 13C NMR from FSO 3H-SbF5-SO2ClF solutions. In synthetic studies, the Bronsted superacid CF3SO3H is found to be an effective acid catalyst for the Knorr cyclization.
- Sai, Kiran Kumar Solingapuram,Gilbert, Thomas M.,Klumpp, Douglas A.
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p. 9761 - 9764
(2008/03/27)
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- 4-Aryl-2-quinolones through a Pseudo-Domino Heck/Buchwald-Hartwig reaction in a molten tetrabutylammonium acetate/ tetrabutylammonium bromide mixture
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4-Aryl-2-quinolones can be prepared from readily available o-bromocinnamamide and aryl iodides using phosphine-free palladium(II) ace-tate as the precatalyst and a molten tetra(n-butyl)-ammonium acetate/tetra(n-butyl) ammonium bro-mide mixture as the reac
- Battistuzzi, Gianfranco,Bernini, Roberta,Cacchi, Sandro,De Salve, Ilse,Fabrizi, Giancarlo
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p. 297 - 302
(2008/02/05)
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- MEDICINAL USE OF RECEPTOR LIGANDS
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Compounds of formula (I) are ligands of the melanin concentrating hormone-1 receptor (MCH-1 R), useful in the treatment of diseases responsive to modulation of melanin concentrating hormone (MCH) activity, for example feeding disorders and diseases for which obesity is a risk factor (I): wherein ring B is selected from specific substituted phenyl or benz-fused 5-membered N-containing heterocycles defined in the specification; R, is attached to a ring carbon of ring B, and represents hydrogen, F, Cl, or -OCH3; X is =CH- or =N-; L, is -CH2- or -CH2CH2- ; L2 is a bond, -CH2- or -CO-; R2 is H or C,-C3 alkyl, or -N(R2) L,- is selected from specific cyclic amino linker radicals as defined in the specification; ring A is selected from specific N- containing heterocyclic rings as defined in the specification.
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Page/Page column 29-30
(2008/06/13)
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- 4-Aryl-2-quinolones via a domino heck reaction/cyclization process
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The reaction of methyl β-(o-acetamidophenyl)acrylates with aryl iodides in the presence of Pd(OAc)2 and KOAc in DMF at 120 °C affords 4-aryl-2-quinolones in allowable to good yields.
- Bernini, Roberta,Cacchi, Sandro,Fabrizi, Giancarlo,Sferrazza, Alessio
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- The Heck reaction of β-arylacrylamides: An approach to 4-aryl-2-quinolones
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The Heck reaction of β-arylacrylamides with aryl iodides afforded the corresponding vinylic substitution products usually in high yields. The nature of β-substituents, aryl iodides and substituents at the nitrogen atom influences the stereochemical outcome. N,N-Dimethyl-β-arylacrylamides gave vinylic substitution products with higher stereoselectivity than the corresponding N-unsubstituted β-arylacrylamides. β-Arylacrylamides containing ortho-substituents led to the formation of only one stereoisomer. The procedure was used to prepare 4-aryl-2-quinolones from β-(obromophenyl) acrylamide through a sequential Heck reaction and copper-catalyzed cyclization process. Georg Thieme Verlag Stuttgart.
- Bernini, Roberta,Cacchi, Sandro,De Salve, Ilse,Fabrizi, Giancarlo
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p. 2947 - 2952
(2008/02/12)
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- Superacidic activation of α,β-unsaturated amides and their electrophilic reactions
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The electrophilic reactivity of α,β-unsaturated amides towards weak nucleophiles such as arenes and cyclohexane, initiated either with triflic acid (CF3SO3H) or with excess AlCl3, has been studied. The amides generally condense readily with aromatics in the presence of AlCl3 to give 3-arylpropionamides and related compounds in excellent yields, while some amides also undergo selective ionic hydrogenation with cyclohexane to give saturated amides. The proposed mechanism of these reactions involves dicationic intermediates (superelectrophiles). The direct observation of a dicationic species (by low-temperature NMR) is reported. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Koltunov, Konstantin Yu.,Walspurger, Stephane,Sommer, Jean
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p. 4039 - 4047
(2007/10/03)
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- Superelectrophilic activation of polyfunctional organic compounds using zeolites and other solid acids
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Zeolites and other available solid acids have been successfully applied to initiate reactions, which were earlier recognised to involve superelectrophilic intermediates and thus required excess of superacids to be carried out.
- Koltunov, Konstantin Yu.,Walspurger, Stéphane,Sommer, Jean
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p. 1754 - 1755
(2007/10/03)
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- Facile synthesis of 4-phenylquinolin-2(1H)-one derivatives from N-acyl-o-aminobenzophenones
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An efficient synthesis of 4-phenylquinolin-2(1H)-one derivatives has been achieved in a one-pot reaction from N-acyl-o-aminobenzophenones 1a-c (a: acyl=acetyl; b: acyl=propanoyl; c: acyl=heptanoyl) using NaH as a base. Treatment of 1 with NaH provided the quinolones 2a-c with 62-83% yields, whereas the reaction in the presence of alkyl iodide (alkyl=methyl, ethyl, n-octyl) gave the corresponding N-alkylated quinolones 3a-g in 75-95% yields. The alkylation reaction of 4-phenylquinolin-2(1H)-one 2a with alkyl halide gave a mixture of N-alkylated and O-alkylated products. Comparison of IR and NMR data of the N-alkylated and O-alkylated compounds with those of 2a-c indicated that 2a-c exist as the lactam form.
- Park, Kwanghee Koh,Lee, Jin Joo
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p. 2993 - 2999
(2007/10/03)
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- Reversibility in Lewis-acid promoted reactions of N-arylcinnamamides
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The Lewis-acid promoted cyclisation reactions of N-arylcinnamamides have been investigated. With aluminium chloride a range of products were obtained, while much more selective cyclisation reactions were observed with bismuth chloride.
- Elliott, Mark C.,Wordingham, Stuart V.
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p. 898 - 900
(2007/10/03)
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- The formation of quinolin-2(1H)-ones via electrocyclic reaction of o-isocyanatostyrenes generated in situ from o-isocyanostyrenes
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A convenient one-pot preparation of 4-substituted or 3,4-disubstituted quinolin-2(1H)-ones from 2-isocyanostyrene derivatives, which involves mCPBA oxidation to the corresponding isocyanate intermediates followed by electrocyclization, is described.
- Kobayashi, Kazuhiro,Kitamura, Taichi,Yoneda, Keiichi,Morikawa, Osamu,Konishi, Hisatoshi
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p. 798 - 799
(2007/10/03)
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- Synthesis and antiplatelet activity of phenyl quinolones
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In our search for novel antiplatelet agents, seven positional phenyl quinolone isomers were synthesized. Preliminary screening confirmed their inhibitory effects against arachidonic acid (AA)-induced platelet aggregation. Varying the substitutional position of the phenyl group had a profound effect on the antiplatelet activity of these isomers. 3-Phenyl-4-quinolone showed the greatest potency and was superior to indomethacin, although the two structures are quite different. The mechanism and pharmacological action of 3-phenyl-4-quinolone are currently under investigation. Copyright (C) 1998 Elsevier Science Ltd.
- Huang, Li-Jiau,Hsieh, Ming-Chieh,Teng, Che-Ming,Lee, Kuo-Hsiung,Kuo, Sheng-Chu
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p. 1657 - 1662
(2007/10/03)
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- Pyridine and related aza heterocycle derivatives as cardiovascular agents
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Novel pharmaceutical compounds and compositions having nitrogen containing ring systems which may be represented by the following structural formula: wherein R1 or R3 is a moiety of the formula: wherein R6 is selected from either hydrogen or acetyl; R7 is selected from 2, 3 or 4-pyridyl or 1-imidazolyl and Q is -(CH2)n, where n is an integer from 1 to 5 and R1 and R2, R2 and R3, R3 and R4 or R4 and R5 taken together may be -CH=CH-CH=CH-. The compounds and compositions are useful as inhibitors of thromboxane synthetase and in the treatment of hypertension and arrythmia in mammals.
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- Synthesis of 2-Hydroxyquinolines from 2-Aminobenzophenones and N,N-Dimethylacetamide
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Substituted 2-hydroxyquinolines were obtained by interaction of 2-aminobenzophenones with N,N-dimethylacetamide under the action of powdered freshly melted potassium hydroxide at room temperature.
- Chorbadjiev, S.
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p. 3497 - 3505
(2007/10/02)
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- On the Mechanism of Thermal Ring Expansion of 3,3-Dialkyloxindoles
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13C Labelling experiments show that the title reaction takes place by a free radical mechanism which involves (i) homolysis of the C(3)-alkyl bond, (ii) rearrangement of the resulting 3-indolyl radical to a 3-indolylmethyl radical , (iii) ring expansion by competitive neophyl rearrangement or attack at the carbonyl position, and (iv) aromatisation by loss of a hydrogen atom.
- McNab, Hamish
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p. 543 - 545
(2007/10/02)
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- Tricyclic heterocyclic compounds as psychopharmaceuticals
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New heterocyclic compounds having the general formula STR1 wherein STR2 CO2 R' or CONR'R", wherein R' and R" independently are C1-6 -alkyl, C3-7 -cycloalkyl or C1-6 -alkoxymethyl; --A-- is --C(=O)--NR'"--, --NR'"--C(=O)--, or STR3 wherein R'" is C1-6 -alkyl; X is C or N; and R4 is hydrogen, halogen, CN, C1-6 -alkyl, C1-6 -alkynyl, trimethylsilyl-C1-6 -alkynyl, aryloxy which may be substituted with halogen, aralkoxy, C3-7 -cycloalkoxy which may be substituted with one or more C1-6 -alkyl groups, or NR""R'"", wherein R"" and R'"" independently are C1-6 -alkoxy or together with the nitrogen atom form a 3-7 membered heterocyclic ring. The compounds are useful in psychopharmaceutical preparations as anticonvulsants, anxiolytics, hypnotics, and nootropics.
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- Rearrangements and Complex Eliminations with 1,5-Benzothiazepin-4-ones
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The 1,5-benzothiazepin-4-ones 3, 5, and 7 - 10 are pyrolyzed (with proton catalysis in part).New or rarely documented rearrangements and complex eliminations occur.These are classified and mechanistically discussed.The products and by-products are spectroscopically characterized (IR, UV, NMR, MS).Their configurations are elucidated via photolysis experiments. 4 photodimerizes in solution and in the crystalline state with great ease to give 14. 11 is remarkably insensitive towards hydrolysis.
- Kaupp, Gerd,Gruendken, Eleonore,Matthies, Doris
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p. 3109 - 3120
(2007/10/02)
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- Synthesis of 3-Arylcoumarins, Thiacoumarins and Carbostyrils
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3-Arylcarbostyrils (2a-f), coumarins (2g-j) and thiacoumarin (2k) have been prepared by a generalised method from α,β-dibromohydrocinnamoyl derivatives (1a-k).The intermediate dihydrocoumarins and dihydrocarbostyrils (3, Y = O, NH) have been prepared which on acid treatment furnish 2.However, treatment of 3 with a base affords the 4-arylcoumarins and carbostyrils (4).
- Natarajan, M.,Manimaran, T.,Ramakrishnan, V. T.
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p. 529 - 534
(2007/10/02)
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- A New Route for the Synthesis of Coumarins, Thiacoumarins and Carbostyrils
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3-Arylcarbostyrils, coumarins and thiacoumarins (3) have been prepared from the respective β-aryl-α-bromodihydrocinnamoyl derivatives (2) by treatment with AlCl3.The β,β-diarylacrylic acid derivatives (4) and (9), obtained from 2, on reaction with AlCl3 afford 4-arylcarbostyrils (5) 6-methyl-4-phenylthiacoumarin (10) respectively.However the oxygen analogs (11) give 3,3-diphenyl-1-indanone (12)
- Natarajan, M.,Ramakrishnan, V. T.
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p. 720 - 727
(2007/10/02)
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