- Synthesis of 2,3-Dihydro-4-pyridones and 4-Pyridones by the Cyclization Reaction of Ester-Tethered Enaminones
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2,3-Dihydro-4-pyridone skeleton is an important building block in organic synthesis because it features several reaction sites with nucleophilic or electrophilic properties. Herein, we disclose a method for its formation by intramolecular cyclization of ester-tethered enaminones, which can easily be synthesized from readily available materials, such as amines, activated alkynes, and activated alkenes. 2,3-Dihydro-4-pyridones have been isolated in 41-90% yields. We also demonstrate the transformation of these heterocycles into another important class of compounds, 4-pyridones, by utilizing 2,3,5,6-tetrachloro-p-benzoquinone (chloranil) as an oxidizing agent. The latter products were isolated in 65-94% yields.
- Stojanovi?, Milovan,Bugarski, Slobodan,Baranac-Stojanovi?, Marija
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p. 13495 - 13507
(2020/11/13)
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- Design, synthesis and biological activity evaluation of novel methyl substituted benzimidazole derivatives
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Ten new dabigatran derivatives (7a–j) with high docking scoring were designed, synthesised and biologically evaluated. The inhibitory in vitro activity of these compounds on thrombin was evaluated on the basis of preliminary activity screening results. The IC50 values of compounds 7a, 7d and 7j were 1.92, 2.17 and 1.54 nM, respectively, and are equivalent to the dabigatran (IC50 = 1.20 nM). Therefore, the most active compound, 7j, was selected to further investigate the anticoagulant activity in rats. Compound 7j presented excellent in vivo inhibitory effects on arteriovenous thrombosis, and the inhibition rate was (84.19 ± 1.14) %. The anticoagulant activity of compound 7k synthesised in the previous work was evaluated in vivo, and its inhibition rate was (85.58 ± 2.89) %. This rate was nearly equivalent to that of dabigatran (85.07 ± 0.61) %. Results indicated that compounds 7a, 7d, 7j and 7k can be further studied as novel antithrombin drug candidates.
- Liu, Qianqian,Ren, Yujie,Zhang, Tianrong
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- Preparation method of 3-(phenyl amino)ethyl propionate type compound
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The invention belongs to the technical field of chemical synthesis and particularly relates to a preparation method of a 3-(phenyl amino)ethyl propionate type compound. The method is realized throughthe following steps: mixing an aromatic amine compound w
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Paragraph 0026
(2018/09/29)
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- A green and convenient approach for the one-pot solvent-free synthesis of coumarins and β-amino carbonyl compounds using Lewis acid grafted sulfonated carbon@titania composite
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Abstract: This paper reports an efficient protocol for the synthesis of coumarins via Pechmann reaction, and β-amino carbonyl compounds via aza-Michael reaction using catalytic amount of solid Lewis acid catalyst, C@TiO2–SO3–SbCl2. Six different catalysts were prepared by covalent immobilization of homogeneous Lewis acids onto sulfonated carbon@titania composite derived from amorphous carbon and nano-titania. Among various catalysts tested, C@TiO2–SO3–SbCl2 showed superior catalytic activity. The catalyst could be recycled without significant loss of its catalytic activity and demonstrated versatile catalysis for a wide range of substrates. Graphical abstract: [Figure not available: see fulltext.]
- Kour, Manmeet,Paul, Satya
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p. 327 - 337
(2017/02/10)
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- Tin-Catalyzed Selective Reductive Hydroamination of Alkynes for the Synthesis of Tertiary Amines
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A unique preference of tin(II) for aniline activation is disclosed. In the present work tin(II) triflate-catalyzed highly selective Markovnikov reductive hydroamination of internal as well as terminal alkynes is reported. The mechanistic study revealed the involvement of two steps in one pot wherein alkyne reduces to corresponding alkene in presence of PMHS as reducing agent followed by hydroamination of alkene. A broad range of alkynes transformed into tertiary amines with good to excellent yield. This method is equally applicable in synthesis of secondary amines.
- Nayal, Onkar S.,Thakur, Maheshwar S.,Kumar, Manoranjan,Sharma, Sushila,Kumar, Neeraj
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p. 1103 - 1109
(2016/04/19)
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- Aza-Michael mono-addition using acidic alumina under solventless conditions
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Aza-Michael reactions between primary aliphatic and aromatic amines and various Michael acceptors have been performed under environmentally-friendly solventless conditions using acidic alumina as a heterogeneous catalyst to selectively obtain the corresponding mono-adducts in high yields. Ethyl acrylate was the main acceptor used, although others such as acrylonitrile, methyl acrylate and acrylamide were also utilized successfully. Bi-functional amines also gave the mono-adducts in good to excellent yields. Such compounds can serve as intermediates for the synthesis of anti-cancer and antibiotic drugs.
- Bosica, Giovanna,Abdilla, Roderick
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- 2 - [6-methoxy-3 - (2,3-dichlorophenyl) methyl-4-oxo -1,4-dihydro -1 (4H)-quinolyl] method for the preparation of acetic acid
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The invention provides a preparation method of 2-(6-methoxy-3-(2, 3-dichlorophenyl) methyl-4-oxo-1, 4-dihydro-1(4H)-quinolyl) acetic acid. The preparation method comprises the following steps: by taking 3-(4-methoxyanilino) sodium propionate as a raw material, performing amino protection treatment to prepare 3-(N-protecting group-4-methoxyanilino) propionic acid, performing Friedel-Crafts acylation reaction to prepare N-protecting group-6-methoxy-2, 3-dihydroquinolinone, and further performing deprotection treatment to prepare an intermediate, namely 6-methoxy-2, 3-dihydro-4 (1H)-quinolinone; by taking the intermediate, namely 6-methoxy-2, 3-dihydro-4 (1H)-quinolinone as a raw material, performing N-alkylation, hydrolysis and condensation reaction to prepare a target product. By adopting the preparation method, the use of a large amount of polyphosphoric acid (PPA) can be avoided, the process is environment-friendly, and the preparation method is more conductive to industrial production.
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Paragraph 0049-0052
(2016/10/08)
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- The zeolite ZSM-5-SO3H catalyzed aza-Michael addition of amines and sulfonamides to electron-deficient alkenes under solventfree conditions
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Aza-Micheal addition of aromatic and aliphatic amines and sulfonamides to α,β-unsaturated esters, ketones and nitriles has been developed using the zeolite ZSM-5-SO3H as catalyst under solvent-free conditions.
- Douraki, Saba Mohammadi,Massah, Ahmad Reza
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p. 1346 - 1349
(2015/11/10)
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- The zeolite ZSM-5-SO3H catalyzed aza-Michael addition of amines and sulfonamides to electron-deficient alkenes under solvent-free conditions
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Aza-Micheal addition of aromatic and aliphatic amines and sulfonamides to α,β-unsaturated esters, ketones and nitriles has been developed using the zeolite ZSM-5-SO3H as catalyst under solvent-free conditions.
- Douraki, Saba Mohammadi,Massah, Ahmad Reza
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p. 1346 - 1349
(2016/02/26)
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- Synthesis and biological evaluation of some new 2,5-Substituted 1-Ethyl-1H-benzoimidazole fluorinated derivatives as direct thrombin Inhibitors
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A new series of fluorinated 2,5-substituted 1-ethyl-1H-benzimidazole derivatives were synthesized from starting compounds 3a-i, which were prepared from acrylic acid ethyl ester and the appropriate amines using trifluoromethanesulfonic acid as a catalyst. A total of 9 novel derivatives were synthesized through 9 steps. All of them were evaluated for thrombin inhibition activity in vitro for the first time. We have altered their structures using different substituents on the amines to assess their structure-activity relationships as direct thrombin inhibitors. All the compounds were effective thrombin inhibitors, with IC50 values ranging from 3.39 to 23.30nM. Among the compounds synthesized, compounds 14a, 14b, 14d, 14e, and 14h exhibited greater anticoagulant activity than argatroban (IC50=9.36nM). Furthermore, compound 14h synthesized starting with 2-amino-pyridine was the most potent thrombin inhibitor with an IC50 value of 3.39nM. Molecular modeling studies were performed to determine the probable interactions of the most potent compounds 14a, 14e, and 14h with their protein receptor (PDB ID: 1KTS). Docking data show that the active compounds inhibit thrombin in a similar mode to that of the potent anticoagulant dabigatran. A new series of fluorinated derivatives were evaluated for their in vitro thrombin inhibition activities. 3-({2-[(4-Carbamimidoyl-2-fluoro-phenylamino)-methyl]-1-ethyl-1H-benzoimidazole-5-carbonyl}-pyridin-2-yl-amino)-propionic acid 14h shows the most potent antithrombin activity (IC50=3.39nM). Molecular docking revealed that its inhibition mode was similar to that of dabigatran.
- Li, Meilin,Ren, Yujie
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p. 353 - 365
(2015/05/13)
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- Titania nanoparticles stabilized HPA in SBA-15 for the intermolecular hydroamination of activated olefins
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A liquid phase hydroamination (HA) of α,β-ethylenic compounds with amines was investigated with TiO2 nanoparticles stabilized 12-tungstophosphoric acid (TPA) in SBA-15. The catalysts were prepared by wet impregnation of TPA/TiO2 nanoparticles into the SBA-15 and calcined at different temperatures. The characterization results reveal that the textural properties and the acidity of the prepared catalysts can be finely controlled with the simple adjustment of the calcination temperature and the structure of the support, decorated with the TiO2 and TPA nanoparticles, was intact even after the modification. The prepared catalysts were investigated for HA of ethyl acrylate with different aromatic and aliphatic amines over a wide range of reaction conditions to optimize the yield and the selectivity of product. It was found that this process is 100% atom efficient and the catalytic performance depended significantly on the loading of TPA over the catalyst and the calcination temperature. Under optimized reaction conditions, the best catalyst, 15 wt%TPA/22.4 wt%TiO2/SBA-15 calcined at 1123 K, offered the highest conversion of p-ethylaniline (70%) with 100% chemo-selectivity to the anti-Markovnikov product, i.e., the mono-addition product. The reaction was heterogeneously catalyzed and no contribution from leached TPA into the reaction was observed.
- Sawant-Dhuri, Dhanashri,Balasubramanian, Veerappan V.,Ariga, Katsuhiko,Park, Dae-Hwan,Choy, Jin-Ho,Cha, Wang Soo,Al-Deyab, Salem S.,Halligudi, Shivappa B.,Vinu, Ajayan
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p. 3347 - 3354
(2015/04/16)
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- Ultrasound-assisted aza-Michael reaction in water: A green procedure
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The conjugate addition of amines to conjugated alkenes (commonly known as aza-Michael reaction) constitutes a key step for the synthesis of various complex natural products, antibiotics, α-amino alcohols and chiral auxiliaries. Ultrasound-induced addition of several amines to α, β-unsaturated ketones, esters and nitriles has been carried out very efficiently in water as well as under solvent-free conditions. No catalysts or solid supports have been used in this method. Remarkable enhancement of reaction rate has been observed in water under ultrasound-induced method. This environmentally benign procedure has provided clean formation of the products with better selectivity.
- Bandyopadhyay, Debasish,Mukherjee, Sanghamitra,Turrubiartes, Luis C.,Banik, Bimal K.
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experimental part
p. 969 - 973
(2012/05/20)
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- One-pot reductive mono-n-alkylation of aromatic nitro compounds using nitriles as alkylating reagents
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A one-pot, simple, selective, and efficient protocol for the synthesis of aromatic secondary amines from various nitro arenes and nitriles in the presence of 10% Pd/C catalyst under H2 at atmospheric pressure and ambient temperature in tetrahydrofuran is illustrated. The scope and limitations of this method have been examined.
- Neogi, Subhasish,Naskar, Dinabandhu
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experimental part
p. 1901 - 1915
(2011/07/08)
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- Microwave-induced aza-michael reaction in water: A remarkably simple procedure
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Microwave-induced fast addition of several amines to conjugated carbonyl compounds has been carried out in water very efficiently in the absence of any catalyst. Copyright
- Kall, Andrea,Bandyopadhyay, Debasish,Banik, Bimal K.
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experimental part
p. 1730 - 1735
(2010/07/14)
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- Preparation of aryl-alkylamines via electrophilic amination of functionalized arylazo tosylates with alkylzinc reagents
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A new electrophilic amination reaction of functionalized arylazo tosylates with alkylzinc halides or dialkylzinc reagents in THF leads to the corresponding hydrazines. A facile cleavage of the N-N bond is achieved using Raney nickel in refluxing ethanol, leading to substituted secondary aryl-alkylamines in 45-79% yield.
- Sinha, Pradipta,Kofink, Christiane C.,Knochel, Paul
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p. 3741 - 3744
(2007/10/03)
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- Cerium(IV) ammonium nitrate (CAN) catalyzed aza-Michael addition of amines to α,β-unsaturated electrophiles
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Cerium(IV) ammonium nitrate (CAN) catalyzed facile and efficient aza-Michael addition of aromatic and aliphatic amines with α,β-unsaturated electrophiles in the absence of solvent under ultrasound irradiation.
- Duan, Zheng,Xuan, Xuejie,Li, Ting,Yang, Chenfei,Wu, Yangjie
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p. 5433 - 5436
(2007/10/03)
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- RuCl3 in poly(ethylene glycol): A highly efficient and recyclable catalyst for the conjugate addition of nitrogen and sulfur nucleophiles
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The 1,4-conjugate addition of primary, secondary and aromatic amines, thiols, and carbamate to α,β-unsaturated compounds mediated by a catalytic amount (0.5 mol%) of RuCl3 in poly(ethylene glycol) (PEG) provides the desired β-substituted carbonyls in high yields. In particular, we found that primary aliphatic and aromatic amines produced the single adducts as the sole products in very high yields with RuCl3-PEG. RuCl 3-PEG was readily recycled via solvent precipitation with efficient recyclability as evidenced by high yields. Its properties of low sensitivity toward moisture and oxygen, high tolerance of different functional groups, and efficient recyclability make RuCl3-PEG suitable for both laboratory and industrial scale synthesis of β-substituted carbonyls. Georg Thieme Verlag Stuttgart.
- Zhang, Huaxing,Zhang, Yuhong,Liu, Leifang,Xu, Hailiang,Wang, Yanguang
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p. 2129 - 2136
(2007/10/03)
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- N-H insertion reactions of rhodium carbenoids. Part 3. The development of a modified Bischler indole synthesis and a new protecting-group strategy for indoles
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A modified version of the Bischler indole synthesis has been developed in which the key step is the N-H insertion reaction of rhodium carbene intermediates derived from α-diazo-β-ketoesters with anilines. Thus N-methylanilines 1 react with diazoketoesters 2 in the presence of dirhodium(II) acetate to give (N-arylamino)ketones 3, cyclisation of which using boron trifluoride-ethyl acetate or acidic ion exchange resin gives the indoles 4. In order to extend this method to the synthesis of N-unsubstituted indoles, a new protecting group strategy for indoles was developed. In this, anilines are reacted with α,β-unsaturated-esters or -sulfones to give the conjugate addition products 6 and 9, cyclisation of which gives indoles 8 and 11. The N-(2-ethoxycarbonylethyl)- and -(2-sulfonylethyl)- protecting groups are readily removed from indoles 8 and 11 by treatment with base.
- Bashford, Katherine E.,Cooper, Anthony L.,Kane, Peter D.,Moody, Christopher J.,Muthusamy, Sendogagounder,Swanna, Elizabeth
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p. 1672 - 1687
(2007/10/03)
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- Studies in Antifertility Agents: Part XXVII - Synthesis of 2-Acetyl-3-aryl-5-tosyl-7/8-H (or methoxy)-3,3a,4,5-tetrahydropyrazoloquinolines
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N-Tosyl-2,3-dihydro-4-quinolones (12-14), prepared from aniline, m- and p-anisidines by reported procedures, on condensation with araldehydes in the presence of NaOMe give the corresponding 3-arylidene-4-quinolones (15-18).Refluxing of 15-18 with NH2-NH2*H2O in gl.AcOH affords the title compounds, 2-acetyl-3-aryl-5-tosyl-7/8-H (or methoxy)-3,3a,4,5-tetrahydropyrazoloquinolines (19-22).The stereochemistry of the title compounds based on the assignments of C3-H, C3a-H, C4-H2 protons has been studied by PMR decoupling experiments.In preliminary screening, compounds 19 and 22 have been found to prevent pregnancy at 20 mg/kg dose in female albino rats, but are ineffective at lower doses.None of the compounds tested shows any significant pharmacological activity.
- Kelkar, Prabhakar M.,Sangwan, Naresh K.,Rastogi, Shri Nivas,Anand, Nitya
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p. 297 - 300
(2007/10/02)
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- Formation of 2,3-Dihydro-4(1H)-quinolones and Related Compounds via Fries-type Acid-catalysed Rearrangement of 1-Arylazetidin-2-ones
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A variety of 1-arylazetidin-2-ones were treated with trifluoroacetic acid under reflux, methanesulphonic acid at 100 deg C, or conc. sulphuric acid to give the corresponding 2,3-dihydro-4(1H)-quinolones via acyl migration and N-CO fission.In the case of 1-(3-substituted phenyl)azetidin-2-ones, two positional isomeric products, 5- and 7-substituted 2,3-dihydro-4(1H)-quinolones were obtained. 4-Methyl, 4-ethoxycarbonyl, and 4-piperidin-2-yl-1-arylazetidin-2-ones and their analogues were also converted into the corresponding 2-substituted 2,3-dihydro-4(1H)-quinolones under acidic conditions.The 3-substituted 1-phenylazetidin-2-ones (36) and (37) were converted into the furoquinoline systems (38) and (40), respectively, by application of this method.
- Kano, Shinzo,Ebata, Tsutomu,Shibuya, Shiroshi
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p. 2105 - 2111
(2007/10/02)
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