- A novel and unusual method for C[sbnd]N bond formation between benzene ring and various amines
-
A new approach to form C[sbnd]N bond without metal catalysis was developed. 4-acetylbenzoyl isocyanate reacted with various amines through a mild method to form C[sbnd]N bond. This reaction was amenable to scale-up and it afforded the corresponding products with good to excellent yields and tolerates a wide range of functional groups.
- Wang, Peng,Wang, Chen,Zhu, Zhenzhen,Xu, Sicong,Hou, Yunlei,Zhao, Yanfang
-
-
- Design, Synthesis and Antitubercular Activity of Novel Isoniazid?Cyclic?Amine?Azachalcones Hybrids
-
In this work, it is described the design of twenty-four heterocyclic amine-azachalcones compounds through molecular hybridization of chalcone scaffold and fragments of isoniazid, fluoroquinolones, and linezolid with antituberculosis potential. The new compounds were synthesized via Claisen-Schmidt condensation, providing yields of 36-95%. Fifteen compounds showed antituberculosis activity against Mycobacterium tuberculosis H37Rv strain. Two amine-azachalcones 15 and 17 showed relevant biological activity with minimum inhibitory concentration (MIC) values of 6.62 and 4.85 μM, respectively. Compound 12 showed the best profile of antitubercular activity with MIC = 9.54 μM and selectivity index (SI) = 9.33. It was found that morpholine group is important to increase potency of antimycobacterial activity but also to add some toxicity to the chalcone molecular framework. The results described herein would be a guide in the designing of novel and optimized antitubercular derivatives based on the chalcone scaffold.
- Barbosa, Sandro L.,Baroni, Adriano C. M.,Croda, Júlio,Gomes, Giovana B.,Guerrero, Palimécio G.,Moreira, Flora M. F.,Oliveira, Jefferson R. S.,Perdomo, Renata T.,Shiguemoto, Cristiane Y. K.,das Neves, Amarith R.
-
p. 1284 - 1295
(2020/10/14)
-
- Preparation method for series synthesis of phenylpyrrolidine derivative under metal catalysis
-
The invention relates to a preparation method for series synthesis of a phenylpyrrolidine derivative under metal catalysis. The structural formula of the prepared phenylpyrrolidine derivative is shownin the figure 1. The preparation method comprises the following steps: preparing an N, N-diallyl aniline compound, a Grubbs catalyst, reduced iron powder and a reaction solvent, setting the reactiontemperature to be 40 DEG C, and fully stirring and reacting for 8-10 hours in a hydrogen atmosphere; and quenching after the reaction is monitored by TLC, extracting by using an organic solvent, drying, filtering, concentrating, and purifying by column chromatography to obtain the phenylpyrrolidine derivative with the yield of 62-81%. According to the method, the phenylpyrrolidine derivative is synthesized through one-pot series connection, raw materials are easy to obtain, operation is easy, repeatability is good, reaction conditions are mild, and the method is suitable for industrial production.
- -
-
Paragraph 0016
(2020/09/16)
-
- Nickel-Catalyzed Amination of (Hetero)aryl Halides Facilitated by a Catalytic Pyridinium Additive
-
An efficient and operationally simple Ni-catalyzed amination protocol has been developed. This methodology features a simple NiII salt, an organic base and catalytic amounts of both a pyridinium additive and Zn metal. A diverse number of (hetero)aryl halides were coupled successfully with primary and secondary alkyl amines, and anilines in good to excellent yields. Similarly, benzophenone imine gave the corresponding N-arylation product in an excellent yield.
- Han, Dongyang,Li, Sasa,Xia, Siqi,Su, Mincong,Jin, Jian
-
supporting information
p. 12349 - 12354
(2020/09/09)
-
- Synthesis and biological evaluation of some novel thiobenzimidazole derivatives as anti-renal cancer agents through inhibition of c-MET kinase
-
Benzimidazole is an interesting scaffold constituting a main core in many anticancer agents against variable cell lines as Carbendazim (I) and Nocodazole (II). Accordingly, eighteen compounds of 2-((1H-benzoimidazol-2-yl)thio)-1-(aryl/heteroaryl)ethan-1-ones, in their sulfate salt and free forms, were designed and investigated as anticancer agents. In vitro preliminary screening of selected compounds by the National Cancer Institute (NCI) on a panel of 60 cell lines revealed renal cancer cell line (A498) as the most vulnerable cell line; accordingly, IC50 values against A498 cell line were determined for compounds with the best results. The best inhibitory activity was for compound 4a with (IC50 = 6.97 μM) compared to sunitinib as a reference drug (IC50 = 6.99 μM). Compound 4a was further subjected to cell cycle analysis that indicated the decrease in cell population in the G2/M phase when compared to the untreated control cells. In addition, it showed significant increase in the late apoptosis in Annexin-V FTIC study compared to the control cells. An enzymatic inhibitory study on compound 4a against c-Met and MAP kinases revealed its better activity against c-Met kinase with (IC50 = 0.27 μM) compared to sunitinib (IC50 = 0.18 μM). Molecular docking study was conducted to reveal the interactions of compound 4a in the active site of c-Met kinase. Computational ADME study was performed to insure that compound 4a has proper pharmacokinetic and drug-likeness properties.
- Ibrahim, Hany S.,Albakri, Mohamed E.,Mahmoud, Walaa R.,Allam, Heba Abdelrasheed,Reda, Ahmed M.,Abdel-Aziz, Hatem A.
-
p. 337 - 348
(2019/01/18)
-
- Application of hydrazino and hydrazido linkers to connect benzenesulfonamides with hydrophilic/phobic tails for targeting the middle region of human carbonic anhydrases active site: Selective inhibitors of hCA IX
-
Herein we report the design and synthesis of three different sets of novel benzenesulfonamides (5a-e, 7a-e and 10a-d) incorporating hydrophilic/hydrophobic tails by hydrazido or hydrazino linkers. The newly synthesized benzenesulfonamides were examined in vitro for their inhibitory activity towards four human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII using a stopped-flow CO2 hydrase assay. All these isoforms were inhibited by the sulfonamides (5a-e, 7a-e and 10a-d) with variable degrees in the following KI ranges: 76.8–357.4 nM for hCA I, 8.2–94.6 nM for hCA II, 2.0–46.3 nM for hCA XI, and 8.3–88.3 nM for hCA XII. The sulfonamide 7d exhibited potent anti-proliferative activity against breast MCF-7 cancer cell line under both normoxic and hypoxic conditions with IC50 values equal 3.32 ± 0.06 and 8.53 ± 0.32 μM, respectively, which are comparable to the reference drug doxorubicin (IC50 = 2.36 ± 0.04 and 8.39 ± 0.25 μM, respectively). Furthermore, 7d was screened for cell cycle disturbance and apoptosis induction in MCF-7 cells. It was found to persuade cell cycle arrest at G2-M stage as well as to alter the Sub-G1 phase, also, 7d resulted in a significant increase in the percent of annexinV-FITC positive apoptotic cells from 1.03 to 18.54%. Molecular docking study was carried out for 7d within the hCA IX and hCA XII active sites to rationalize the obtained inhibition results.
- Allam, Heba Abdelrasheed,Fahim, Samar H.,F.Abo-Ashour, Mahmoud,Nocentini, Alessio,Elbakry, Mohamed E.,Abdelrahman, Mohamed A.,Eldehna, Wagdy M.,Ibrahim, Hany S.,Supuran, Claudiu T.
-
p. 547 - 556
(2019/07/04)
-
- Practical heterogeneous photoredox/nickel dual catalysis for C-N and C-O coupling reactions
-
Efficient C-N and C-O coupling reactions of aryl halides with amines and alcohols have been developed by using the strategy of heterogeneous visible light photoredox and nickel dual catalysis. Obviously, the joint use of inexpensive and bench-stable CdS and nickel salts, together with mild reaction conditions, makes these two transformations attractive for the synthetic community. This heterogeneous dual catalysis system also proved to be successful in the ligand-free catalytic hydroxylation of aryl bromide with water as a nucleophile. The practicality of this protocol is further emphasized by the scaled-up reaction and the reusability of heterogeneous photocatalysts.
- Liu, Yi-Yin,Liang, Dong,Lu, Liang-Qiu,Xiao, Wen-Jing
-
supporting information
p. 4853 - 4856
(2019/05/02)
-
- Design, synthesis and biological evaluation of novel aryldiketo acids with enhanced antibacterial activity against multidrug resistant bacterial strains
-
Antimicrobial resistance (AMR) is a major health problem worldwide, because of ability of bacteria, fungi and viruses to evade known therapeutic agents used in treatment of infections. Aryldiketo acids (ADK) have shown antimicrobial activity against several resistant strains including Gram-positive Staphylococcus aureus bacteria. Our previous studies revealed that ADK analogues having bulky alkyl group in ortho position on a phenyl ring have up to ten times better activity than norfloxacin against the same strains. Rational modifications of analogues by introduction of hydrophobic substituents on the aromatic ring has led to more than tenfold increase in antibacterial activity against multidrug resistant Gram positive strains. To elucidate a potential mechanism of action for this potentially novel class of antimicrobials, several bacterial enzymes were identified as putative targets according to literature data and pharmacophoric similarity searches for potent ADK analogues. Among the seven bacterial targets chosen, the strongest favorable binding interactions were observed between most active analogue and S. aureus dehydrosqualene synthase and DNA gyrase. Furthermore, the docking results in combination with literature data suggest that these novel molecules could also target several other bacterial enzymes, including prenyl-transferases and methionine aminopeptidase. These results and our statistically significant 3D QSAR model could be used to guide the further design of more potent derivatives as well as in virtual screening for novel antibacterial agents.
- Cvijeti?, Ilija N.,Verbi?, Tatjana ?.,Ernesto de Resende, Pedro,Stapleton, Paul,Gibbons, Simon,Jurani?, Ivan O.,Drakuli?, Branko J.,Zloh, Mire
-
p. 1474 - 1488
(2017/11/17)
-
- Exploring Tandem Ruthenium-Catalyzed Hydrogen Transfer and SNAr Chemistry
-
A hydrogen-transfer strategy for the catalytic functionalization of benzylic alcohols via electronic arene activation, accessing a diverse range of bespoke diaryl ethers and aryl amines in excellent isolated yields (38 examples, 70% average yield), is reported. Taking advantage of the hydrogen-transfer approach, the oxidation level of the functionalized products can be selected by judicious choice of simple and inexpensive additives.
- Polidano, Kurt,Reed-Berendt, Benjamin G.,Basset, Ana?s,Watson, Andrew J. A.,Williams, Jonathan M. J.,Morrill, Louis C.
-
p. 6716 - 6719
(2017/12/26)
-
- Discovery of N-(Naphthalen-1-yl)-N′-alkyl Oxalamide Ligands Enables Cu-Catalyzed Aryl Amination with High Turnovers
-
A class of N-(naphthalen-1-yl)-N′-alkyl oxalamides have been proven to be powerful ligands, making a coupling reaction of (hetero)aryl iodides with primary amines proceed at 50 °C with only 0.01 mol % of Cu2O and ligand as well as a coupling reaction of (hetero)aryl bromides with primary amines and ammonia at 80 °C with only 0.1 mol % of Cu2O and ligand. A wide range of coupling partners work well under these conditions, thereby providing an easy to operate method for preparing (hetero)aryl amines.
- Gao, Jie,Bhunia, Subhajit,Wang, Kailiang,Gan, Lu,Xia, Shanghua,Ma, Dawei
-
supporting information
p. 2809 - 2812
(2017/06/07)
-
- Asymmetric Reduction of Electron-Rich Ketones with Tethered Ru(II)/TsDPEN Catalysts Using Formic Acid/Triethylamine or Aqueous Sodium Formate
-
The asymmetric transfer hydrogenation (ATH) of ketones under aqueous conditions using tethered Ru(II)/6-arene/diamine catalysts is described, as is the ATH of electron-rich substrates containing amine and methoxy groups on the aromatic rings. Although such substrates are traditionally challenging ones for ATH, the tethered catalysts work very efficiently. In the case of amino-substituted ketones, aqueous conditions give excellent results; however, for methoxy-substituted substrates, the more established formic acid/triethylamine system gives superior results.
- Soni, Rina,Hall, Thomas H.,Mitchell, Benjamin P.,Owen, Matthew R.,Wills, Martin
-
p. 6784 - 6793
(2015/10/06)
-
- N-(1-Oxy-2-picolyl)oxalamic Acid as an Efficient Ligand for Copper-Catalyzed Amination of Aryl Iodides at Room Temperature
-
N-(1-Oxy-pyridin-2-ylmethyl)oxalamic acid was identified as efficient ligand for CuI-catalyzed amination of aryl halides at room temperature. In our catalytic system, N-arylation of cyclic secondary amines, primary amines, amino acids, and ammonia proceeded with moderate to excellent yields and high functional group tolerance.
- Wang, Yongbin,Ling, Jing,Zhang, Yu,Zhang, Ao,Yao, Qizheng
-
p. 4153 - 4161
(2015/07/01)
-
- Ligand-free N-arylation of heterocycles using metal-organic framework [Cu(INA)2] as an efficient heterogeneous catalyst
-
A metal-organic framework [Cu(INA)2] was synthesized and used as a heterogeneous catalyst for arylation of a wide range of N-H heterocycles and aryl halides under ligand-free conditions. The N-arylation reaction involved the use of 5 mol% Cu-MOF catalyst with K3PO4 or tBuOLi as the base in dimethylacetamide (DMA) solvent at 100 °C in 6 h. [Cu(INA)2] exhibited higher catalytic activity for the N-arylation transformation than that of common homogeneous copper catalysts and other Cu-MOFs with unsaturated open metal sites such as Cu2(BDC)2(BPY), Cu3(BTC)2, and Cu2(BDC)2(DABCO). Interestingly, reaction conditions are compatible with a wide range of N-H heterocycles, functional groups, and aryl chlorides. A leaching test indicated no contribution of leached active species in the reaction filtrate. Furthermore, the [Cu(INA)2] catalyst could be facilely separated from the reaction mixture and recovered and reused several times without a significant degradation in catalytic activity.
- Truong, Thanh,Nguyen, Chi V.,Truong, Ngoc T.,Phan, Nam T. S.
-
p. 107547 - 107556
(2016/01/09)
-
- 5-Aryl-1H-pyrazole-3-carboxylic acids as selective inhibitors of human carbonic anhydrases IX and XII
-
Inhibitory activity of a congeneric set of 23 phenyl-substituted 5-phenyl-pyrazole-3-carboxylic acids toward human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms I, II, IX and XII was evaluated by a stopped-flow CO2 hydrase assay. These compounds exerted a clear, selective inhibition of hCA IX and XII over hCAI and II, with Ki in two to one digit micromolar concentrations (4-50 μM). Derivatives bearing bulkier substituents in para-position of the phenyl ring inhibited hCA XII at one-digit micromolar concentrations, while derivatives having alkyl substituents in both ortho- and meta-positions inhibited hCA IX with Kis ranging between 5 and 25 μM. Results of docking experiments offered a rational explanation on the selectivity of these compounds toward CA IX and XII, as well as on the substitution patterns leading to best CA IX or CA XII inhibitors. By examining the active sites of these four isoforms with GRID generated molecular-interaction fields, striking differences between hCA XII and the other three isoforms were observed. The field of hydrophobic probe (DRY) appeared significantly different in CA XII active site, comparing to other three isoforms studied. To the best of our knowledge such an observation was not reported in literature so far. Considering the selectivity of these carboxylates towards membrane-associated over cytosolic CA isoforms, the title compounds could be useful for the development of isoform-specific non-sulfonamide CA inhibitors.
- Cvijeti?, Ilija N.,Tan?, Muhammet,Jurani?, Ivan O.,Verbi?, Tatjana ?.,Supuran, Claudiu T.,Drakuli?, Branko J.
-
p. 4649 - 4659
(2015/08/03)
-
- Magnetic silica supported copper: A modular approach to aqueous Ullmann-type amination of aryl halides
-
One-pot synthesis of a magnetic silica supported copper catalyst has been described via in situ generated magnetic silica (Fe3O 4@SiO2); the catalyst can be used for the efficacious amination of aryl halides in aqueous medium under microwave irradiation.
- Nasir Baig,Varma, Rajender S.
-
p. 6568 - 6572
(2014/02/14)
-
- Ruthenium-catalyzed transfer hydrogenation of amino- and amido-substituted acetophenones
-
The ruthenium-catalyzed transfer hydrogenation of electron-rich amino-substituted acetophenones is reported. Variation of the reductant, ligands, base, and solvent allowed reaction optimization. A key discovery was the use of 1,4-butanediol as an irreversible reducing agent, which significantly improved the conversion. A range of amino- and amido-substituted aryl ketones were explored, and they all gave the corresponding alcohols in good yield, which demonstrates the wider applicability of this process. The ruthenium-catalyzed reduction of electron-rich amino-substituted acetophenones with 1,4-butanediol as an irreversible reducing agent is reported. Optimization of the conditions and variation of the amino substituent are explored as is the use of amido- and sulfonamidoacetophenones with varying results. Copyright
- Watson, Andrew J. A.,Fairbanks, Antony J.
-
supporting information
p. 6784 - 6788
(2013/11/06)
-
- Synthesis and structural characterization of palladium(II) thiosemicarbazone complex: Application to the Buchwald-Hartwig amination reaction
-
A simple route to synthesize mononuclear palladium(II) thiosemicarbazone complex has been described. Elemental analysis, spectral methods and single crystal X-ray diffraction analysis were used to confirm the composition of the complex. The new complex acts as an active homogeneous catalyst for the Buchwald-Hartwig amination reaction of a wide range of aryl and heteroaryl halides (bromides and chlorides), including activating, neutral and deactivating substrates, with various secondary amines under optimized conditions.
- Prabhu, Rupesh Narayana,Ramesh, Rengan
-
p. 1120 - 1124
(2013/03/13)
-
- Antimalarial Activity of Newly Synthesized Chalcone Derivatives In Vitro
-
Twenty-seven novel chalcone derivatives were synthesized using Claisen-Schmidt condensation and their antimalarial activity against asexual blood stages of Plasmodium falciparum was determined. Antiplasmodial IC50 (half-maximal inhibitory concentration) activity of a compound against malaria parasites in vitro provides a good first screen for identifying the antimalarial potential of the compound. The most active compound was 1-(4-benzimidazol-1-yl-phenyl)-3-(2, 4-dimethoxy-phenyl)-propen-1-one with IC50 of 1.1μg/mL, while that of the natural phytochemical, licochalcone A is 1.43μg/mL. The presence of methoxy groups at position 2 and 4 in chalcone derivatives appeared to be favorable for antimalarial activity as compared to other methoxy-substituted chalcones. Furthermore, 3, 4, 5-trimethoxy groups on chalcone derivative probably cause steric hindrance in binding to the active site of cysteine protease enzyme, explaining the relative lower inhibitory activity.
- Yadav, Neesha,Dixit, Sandeep K.,Bhattacharya, Amit,Mishra, Lokesh C.,Sharma, Manish,Awasthi, Satish K.,Bhasin, Virendra K.
-
experimental part
p. 340 - 347
(2012/08/29)
-
- Amination of electron deficient aryl chlorides promoted by nano sized Mg(OH)2 under transition metals free condition
-
This paper presents the amination reactions of electron deficient aryl chlorides promoted by Mg(OH)2 without transition metals. Only using stoichiometric amount of nano sized Mg(OH)2, good to moderate isolated yields could be achieved in N-methylpyrrolidone (NMP) after 24 h at 150 °C.
- Cui, Zhi Hao,Meng, Zi Hui,Mi, Yan Qing,Wang, Peng,Wang, Qi,Zhao, Lin Man,Cui, Ke Jian,Yu, Fang,Xu, Zhi Bin
-
experimental part
p. 137 - 140
(2012/06/18)
-
- Microwave-assisted convenient synthesis of N-arylpyrrolidines in water
-
An efficient and clean synthesis of N-arylpyrrolidines from arylamines and 1,4-dimesyloxybutane was developed using microwave irradiation in an aqueous potassium carbonate medium without any catalyst. The procedure is rapid, simple and convenient.
- Li, Hong Bo,Liang, Wu,Liu, Lang,Chen, Kai,Wu, Yi
-
experimental part
p. 276 - 279
(2012/01/05)
-
- Synthesis of 5-aryl-5′-formyl-2,2′-bithiophenes as new precursors for nonlinear optical (NLO) materials
-
A series of formyl-substituted 5-aryl-2,2′-bithiophenes 5 were synthesized using two different methods: Vilsmeier-Haack-Arnold reaction (VHA) or through Suzuki coupling. The synthesis of compounds 5 through the Vilsmeier-Haack-Arnold reaction, starting from inexpensive and easily available precursors such as acetophenones, gave the title compounds in low yields after four reaction steps. On the other hand Suzuki coupling of functionalized arylboronic acids 7 and the 5-bromo-5′-formyl-2,2′-bithiophene 6 gave compounds 5 in good yields in only one step.
- Herbivo, Cyril,Comel, Alain,Kirsch,Raposo, M. Manuela M.
-
experimental part
p. 2079 - 2086
(2009/07/18)
-
- Synthesis of novel substituted 1,3-diaryl propenone derivatives and their antimalarial activity in vitro
-
The synthesis of novel 1,3-diaryl propenone derivatives and their antimalarial activity in vitro against asexual blood stages of human malaria parasite, Plasmodium falciparum, are described. Chalcone derivatives were prepared via Claisen-Schmidt condensation of substituted aldehydes with substituted methyl ketones. Antiplasmodial IC50 (half maximal inhibitory concentration) activity of these compounds ranged between 1.5 and 12.3 μg/ml. The chloro-series, 1,2,4-triazole substituted chalcone was found to be the most effective in inhibiting the growth of P. falciparum in vitro while pyrrole and benzotriazole substituted chalcones showed relatively less inhibitory activity. This is the first report on antiplasmodial activity of chalcones with azoles on acetophenone ring.
- Mishra, Nidhi,Arora, Preeti,Kumar, Brajesh,Mishra, Lokesh C.,Bhattacharya, Amit,Awasthi, Satish K.,Bhasin, Virendra K.
-
p. 1530 - 1535
(2008/09/21)
-
- Structure-activity relationship study of a novel necroptosis inhibitor, necrostatin-7
-
Necroptosis is a regulated caspase-independent cell death mechanism characterized by morphological features resembling non-regulated necrosis. Necrotatin-7 (Nec-7), a novel potent small-molecule inhibitor of necroptosis, is structurally distinct from previously described necrostatins (Nec-1, Nec-3, Nec-4 and Nec-5). Here, we describe a series of structural modifications and the structure-activity relationship (SAR) of the Nec-7 series for inhibiting necroptosis.
- Zheng, Weihong,Degterev, Alexei,Hsu, Emily,Yuan, Junying,Yuan, Chengye
-
body text
p. 4932 - 4935
(2009/05/26)
-
- Study of the microwave-assisted hydrolysis of nitriles and esters and the implementation of this system in rapid microwave-assisted Pd-catalyzed amination
-
Microwave-assisted hydrolysis of benzonitriles and methyl benzoates has been studied using a toluene/concd aq KOH two phase system in the presence and absence of phase transfer catalyst. Conditions to allow and avoid smooth hydrolysis could be identified. Based on the latter, the first microwave protocol which allows the rapid Pd-catalyzed amination of aliphatic amines with chlorobenzenes containing sensitive functional groups has been developed.
- Van Baelen, Gitte,Maes, Bert U.W.
-
p. 5604 - 5619
(2008/09/21)
-
- Aqueous N-heterocyclization of primary amines and hydrazines with dihalides: Microwave-assisted syntheses of N-azacycloalkanes, isoindole, pyrazole, pyrazolidine, and phthalazine derivatives
-
The synthesis of nitrogen-containing heterocycles from alkyl dihalides (ditosylates) and primary amines and hydrazines via a simple and efficient cyclocondensation in an alkaline aqueous medium that occurs under microwave irradiation is described. This improved greener synthetic methodology provides a simple and straightforward one-pot approach to the synthesis of a variety of heterocycles, such as substituted azetidines, pyrrolidines, piperidines, azepanes, N-substituted 2,3-dihydro-1H-isoindoles, 4,5-dihydropyrazoles, pyrazolidines, and 1,2-dihydrophthalazines.
- Ju, Yuhong,Varma, Rajender S.
-
p. 135 - 141
(2007/10/03)
-
- Amino acid promoted CuI-catalyzed C-N bond formation between aryl halides and amines or N-containing heterocycles
-
CuI-catalyzed coupling reaction of electron-deficient aryl iodides with aliphatic primary amines occurs at 40 °C under the promotion of N-methylglycine. Using L-proline as the promoter, coupling reaction of aryl iodides or aryl bromides with aliphatic primary amines, aliphatic cyclic secondary amines, or electron-rich primary arylamines proceeds at 60-90 °C; an intramolecular coupling reaction between aryl chloride and primary amine moieties gives indoline at 70 °C; coupling reaction of aryl iodides with indole, pyrrole, carbazole, imidazole, or pyrazole can be carried out at 75-90 °C; and coupling reaction of electron-deficient aryl bromides with imidazole or pyrazole occurs at 60-90 °C to provide the corresponding N-aryl products in good to excellent yields. In addition, N,N-dimethylglycine promotes the coupling reaction of electron-rich aryl bromides with imidazole or pyrazole to afford the corresponding N-aryl imidazoles or pyrazoles at 110 °C. The possible action of amino acids in these coupling reactions is discussed.
- Zhang, Hui,Cai, Qian,Ma, Dawei
-
p. 5164 - 5173
(2007/10/03)
-
- 2-Hydroxymethyl-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl] -1-benzenesulfonamide (DRF-4367): An orally active COX-2 inhibitor identified through pharmacophoric modulation
-
Analogs of 1,5-diarylpyrazoles with a novel pharmacophore at N1 were designed, synthesized and evaluated for the in-vitro cyclooxygenase (COX-1/COX-2) inhibitory activity. The variations at/around position-4 of the C-5 phenyl ring in conjunction with a CF3 and CHF2 groups at C-3 exhibited a high degree of potency and selectivity index (SI) for COX-2 inhibition. The in-vivo evaluation of these potent compounds with a few earlier ones indicated the 4-OMe-phenyl analog 6 and the 4-NHMe-phenyl analog 9 with a CF3, and the 4-OEt-phenyl analog 19 with a CHF2 group at C-3 to possess superior potency than celecoxib. In addition to its impressive anti-inflammatory, antipyretic, analgesic and anti-arthritic properties, compound 6 (DRF-4367) was found to possess an excellent pharmacokinetic profile, gastrointestinal (GI) safety in the long-term arthritis study and COX-2 potency in human whole blood assay. Thus, compound 6 was selected as an orally active anti-inflammatory candidate for pre-clinical evaluation.
- Singh, Sunil Kumar,Vobbalareddy, Saibaba,Kalleda, Srinivasa Rao,Rajjak, Shaikh Abdul,Casturi, Seshagiri Rao,Datla, Srinivasa Raju,Mamidi, Rao N.V.S.,Mullangi, Ramesh,Bhamidipati, Ravikanth,Ramanujam, Rajagopalan,Akella, Venkateswarlu,Yeleswarapu, Koteswar Rao
-
p. 2442 - 2450
(2007/10/03)
-
- Reductive one batch synthesis of N-substituted pyrrolidines from primary amines and 2,5-dimethoxytetrahydrofuran
-
The construction of the pyrrolidine ring about a nitrogen of a primary amine by a reductive condensation reaction using 2,5- dimethoxytetrahydrofuran and sodium borohydride in acidic water medium is described. The reaction is fast, affords good to excellent yields and appears insensitive to electron effects and severe steric hindrance; it is found to be compatible with a large variety of aryl substituents, including nitro and oxo groups. The reaction allows the introduction of two deuterium atoms, with label conservation, in both the α-positions of the pyrrolidine ring by the use of sodium borodeuteride instead of sodium borohydride.
- Verardo, Giancarlo,Dolce, Anna,Toniutti, Nicoletta
-
-
- An improved method for the palladium-catalyzed amination of aryl triflates
-
Aryl triflates are coupled with amines using catalytic amounts of Pd(OAc)2 and BINAP and Cs2CO3 as a stoichiometric base. This protocol allows for the efficient amination of electron-poor as well as electron-rich aryl triflates and the reaction conditions are compatible with a wide variety of functional groups.
- Ahman, Jens,Buchwald, Stephen L.
-
p. 6363 - 6366
(2007/10/03)
-
- Aromatic Nucleophilic Substitution of Halobenzenes with Amines under High Pressure
-
The nucleophilic substitution reactions of aromatic halides having electron-attracting groups on ortho or para position with various primary and secondary amines were accelerated by high pressure to give the corresponding N-substituted anilines in high yields.The bulkiness of amines affects its reactivity to lower the yields of the products.Although the secondary amines are usually less reactive than primary amines, cyclic secondary amines such as morpholine, piperidine, and pyrrolidine were found very reactive. 1,4-Diazabicyclooctane and quinuclidine gave N-quarternary ammonium halides in high yields in contrast to the low reactivity of acyclic tertiary amines.Dichloro- and trichloro-nitrobenzenes also react with diethylamine, pyrrolidine, and morpholine to give mono-, di-, and trisubstitution products depending upon the amount of amine and the position of nitro group in these chlorides.
- Ibata, Toshikazu,Isogami, Yasushi,Toyoda, Jiro
-
-
- Nucleophilic Substitution of Aromatic Halides with Amines under High Pressure
-
The reaction of aromatic chlorides, bromides and iodides with various primary or secondary amines in a tetrahydrofuran solution under high pressure of 6-12 kbar gave the corresponding secondary and tertiary aromatic amines. 1,4-Diazabicyclooctane and quinuclidine gave N-aryl quaternary ammonium halides in high yields in contrast to the low reactivity of acyclic tertiary amines.
- Ibata, Toshikazu,Isogami, Yasushi,Toyoda, Jiro
-
p. 1187 - 1190
(2007/10/02)
-