- Direct, Late-Stage Mono-N-arylation of Pentamidine: Method Development, Mechanistic Insight, and Expedient Access to Novel Antiparastitics against Diamidine-Resistant Parasites
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A selective mono-N-arylation strategy of amidines under Chan-Lam conditions is described. During the reaction optimization phase, the isolation of a mononuclear Cu(II) complex provided unique mechanistic insight into the operation of Chan-Lam mono-N-arylation. The scope of the process is demonstrated, and then applied to access the first mono-N-arylated analogues of pentamidine. Sub-micromolar activity against kinetoplastid parasites was observed for several analogues with no cross-resistance in pentamidine and diminazene-resistant trypanosome strains and against Leishmania mexicana. A fluorescent mono-N-arylated pentamidine analogue revealed rapid cellular uptake, accumulating in parasite nuclei and the kinetoplasts. The DNA binding capability of the mono-N-arylated pentamidine series was confirmed by UV-melt measurements using AT-rich DNA. This work highlights the potential to use Chan-Lam mono-N-arylation to develop therapeutic leads against diamidine-resistant trypanosomiasis and leishmaniasis.
- Robertson, Jack,Ungogo, Marzuq A.,Aldfer, Mustafa M.,Lemgruber, Leandro,McWhinnie, Fergus S.,Bode, Bela E.,Jones, Katherine L.,Watson, Allan J. B.,de Koning, Harry P.,Burley, Glenn A.
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supporting information
p. 3396 - 3401
(2021/09/06)
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- Transition-Metal-Free Synthesis of 1,2-diphenyl-1H-benzo[d] Imidazole Derivatives from N-phenylbenzimidamides and Cyclohexanones
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A transition-metal-free strategy for the formation of 1,2-diphenyl-1H-benzo[d] imidazoles from N-phenylbenzimidamides and cyclohexanones is introduced. This is the first report on the direct synthesis of 1,2-diphenyl-1H-benzo[d] imidazoles from cyclohexanones and N-phenylbenzimidamides via iodine- promoted oxidative cyclization. Non-aromatic cyclohexanones were smoothly dehydrogenated, and acted as an aryl source using oxygen as a green oxidant. The catalytic use of iodine makes this method quite simple, more economical and convenient. Under optimized conditions, various substituted 1,2-diphenyl-1H-benzo[d] imidazoles were smoothly reacted, and the desired substituted imidazoles were generated with moderate to excellent yields. (Figure presented.).
- Lu, Guoqiang,Luo, Nan,Hu, Fangpeng,Ban, Zihui,Zhan, Zhenzhen,Huang, Guo-Sheng
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supporting information
p. 487 - 492
(2019/12/12)
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- Synthesis of 1,2-dihydro-1,3,5-triazine derivativesviaCu(ii)-catalyzed C(sp3)-H activation ofN,N-dimethylethanolamine with amidines
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1,2-Dihydro-1,3,5-triazines and symmetrical 1,3,5-triazines were obtained in up to 81% yields from amidines andN,N-dimethylethanolamine catalyzed by CuCl2. The reaction involves three C-N bond formations during the oxidative annulation process
- Chen, Rener,Ma, Renchao,Ma, Yongmin,Wang, Lei,Wang, Zhiming,Yan, Min
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supporting information
p. 10946 - 10949
(2020/10/02)
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- Eco-friendly Synthesis of 3-(Aryl)-2,6-diphenylpyrimidin-4(3H)-ones, Ethyl-1-(aryl)-1,6-dihydro-2-(aryl)-6-oxopyrimidine-4-carboxylates and 6-(4-Arylphenyl)-2-isopropylpyrimidin-4(3H)-one
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In present communication, we report the synthesis of pyrimidin-4(3H)-one derivatives by microwave irradiation in good yields and less reaction time. All titled compounds were characterized by IR, NMR and Mass spectral analyses.
- Anantoju, Kishore Kumar,Eppakayala, Laxminarayana,Maringanti, Thirumala Chary
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p. 845 - 850
(2019/03/07)
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- Acid-catalyzed synthesis of imidazole derivatives via N-phenylbenzimidamides and sulfoxonium ylides cyclization
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A straightforward method to synthesize imidazole derivatives from amidines and sulfoxonium ylides catalyzed by acids is reported in this study. Specifically, catalyzed by trifluoroacetic acid in DCE solvents can improve synthesis efficiency under metal-fr
- Tian, Yuan,Qin, Mingda,Yang, Xueying,Zhang, Xueguo,Liu, Yafeng,Guo, Xin,Chen, Baohua
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supporting information
p. 2817 - 2823
(2019/04/13)
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- Metal-Free C-B Bond Cleavage: An Acid Catalyzed Three-Component Reaction Construction of Imidazole-Containing Triarylmethanes
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An efficient acid-catalyzed strategy to prepare imidazole-containing triarylmethanes from amidines, ynals, and boronic acids has been developed. It represents an unprecedented and novel metal-free C-B bond cleavage strategy as a workable route to form new carbon-carbon bonds.
- Wang, Changcheng,Yu, Yue,Su, Zhengquan,Li, Xuechen,Cao, Hua
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supporting information
p. 4420 - 4423
(2019/06/27)
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- Transition-metal-free three-component reaction: Additive controlled synthesis of sulfonylated imidazoles
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Two efficient transition-metal-free highly regioselective pathways for constructing sulfonylated imidazoles via three-component reactions of amidines, ynals, and sodium sulfonates have been developed. The generations of different sulfonylated imidazoles w
- Liu, Wei,Zhang, Yu,He, Jiaming,Yu, Yue,Yuan, Jiajun,Ye, Xiaoyi,Zhang, Ziwu,Xue, Liang,Cao, Hua
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p. 11348 - 11358
(2019/09/09)
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- N-Heterocyclic carbene-catalyzed annulation of ynals with amidines: Access to 1,2,6-trisubstituted pyrimidin-4-ones
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An N-heterocyclic carbene-catalyzed annulation of ynals and amidines has been reported to construct pyrimidin-4-ones. The protocol features a broad substrate scope and mild conditions. Furthermore, an oxidative strategy to catalytically generate ynal-deri
- Xie, Yangxi,Wang, Jian
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p. 4597 - 4600
(2018/05/14)
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- Direct Synthesis of 3-Acylindoles through Rhodium(III)-Catalyzed Annulation of N-Phenylamidines with α-Cl Ketones
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In the present study, a novel synthetic strategy to directly produce versatile 3-acylindoles through Rh(III)-catalyzed C-H activation and annulation cascade of N-phenylamidines with α-Cl ketones was developed, in which α-Cl ketones serve as unusual one-carbon (sp3) synthons. This strategy features high regioselectivity, efficiency, wide substrate tolerance, and mild reaction conditions, which further underscore its synthetic utility in drug molecule synthesis.
- Zhou, Jianhui,Li, Jian,Li, Yazhou,Wu, Chenglin,He, Guoxue,Yang, Qiaolan,Zhou, Yu,Liu, Hong
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supporting information
p. 7645 - 7649
(2018/12/11)
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- Vanadium-Catalyzed Oxidative C(CO)-C(CO) Bond Cleavage for C-N Bond Formation: One-Pot Domino Transformation of 1,2-Diketones and Amidines into Imides and Amides
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A novel vanadium-catalyzed one-pot domino reaction of 1,2-diketones with amidines has been identified that enables their transformation into imides and amides. The reaction proceeds by dual acylation of amidines via oxidative C(CO)-C(CO) bond cleavage of 1,2-diketones to afford N,N′-diaroyl-N-arylbenzamidine intermediates. In the reaction, these intermediates are easily hydrolyzed into imides and amides through vanadium catalysis. This method provides a practical, simple, and mild synthetic approach to access a variety of imides as well as amides in high yields. Moreover, one-step construction of imide and amide bonds with a long-chain alkyl group is an attractive feature of this protocol.
- Digwal, Chander Singh,Yadav, Upasana,Ramya, P. V. Sri,Sana, Sravani,Swain, Baijayantimala,Kamal, Ahmed
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p. 7332 - 7345
(2017/07/26)
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- Silver-catalyzed [3 + 2] domino reaction: An efficient strategy to synthesize imidazole-5-carbaldehydes
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An unprecedented regioselective silver-catalyzed [3 + 2] domino reaction of amidines and ynals for the formation of C-N bonds has been developed. The reaction provided a new route to prepare imidazole-5-carbaldehydes which are important intermediates for the construction of fine chemicals. The reaction proceeds smoothly with a broad range of substrates to give imidazoles in good yields.
- Wang, Changcheng,Jiang, Hangqi,Chen, Weifeng,Dong, Jun,Chen, Zhengwang,Cao, Hua
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supporting information
p. 6463 - 6466
(2017/08/16)
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- Substrate-Controlled Selectivity Switch in a Three-Component Reaction: A Ag-Catalyzed Strategy for the Synthesis of Functionalized Imidazoles
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An efficient Ag-catalyzed three-component reaction of amidines, ynals, and alcohols, phenols, or water has been developed. This strategy provides a wide range of substrates and represents a simple process for the preparation of different imidazole derivatives in good yields with high regioselectivities.
- Wang, Changcheng,Wang, Enming,Chen, Weixin,Zhang, Lijuan,Zhan, Haiying,Wu, Yuanheng,Cao, Hua
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p. 9144 - 9153
(2017/09/11)
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- Copper-Catalyzed Intramolecular C-H Amination: A New Entry to Substituted Xanthine Derivatives
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Catalytic synthesis of xanthines was achieved in the presence of a copper catalyst. The process involves copper-catalyzed intramolecular C-H amination of benzamidines that possess a uracil moiety and produces variously substituted xanthines generally in good to high yields. This work introduces a new, facile approach to polysubstituted xanthine compounds..
- Shimizu, Maki,Hayama, Noboru,Kimachi, Tetsutaro,Inamoto, Kiyofumi
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p. 4183 - 4190
(2017/09/12)
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- Sulfated tungstate catalyzed activation of nitriles: addition of amines to nitriles for synthesis of amidines
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An efficient and mild method for the synthesis of amidines by direct nucleophilic addition of amines to nitriles using sulfated tungstate as heterogeneous catalyst is described. Highlight of the method is its applicability for the synthesis of amidines using a wide variety of amines including ammonia as ammonium acetate and nitriles. Catalyst is mildly acidic, stable, easy to prepare and separate from the reaction mass.
- Veer, Sachin D.,Katkar, Kamlesh V.,Akamanchi, Krishnacharya G.
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supporting information
p. 4039 - 4043
(2016/08/18)
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- Trimethylaluminium-mediated reaction of primary carboxamides with amines and indoles: A convenient synthesis of amidines and indole-3-acylimines
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A simple, convenient and general method, exhibiting good functional group tolerance, is described for the synthesis of N- and N,N-disubstituted amidines by the reaction of primary carboxamides with amines mediated by trimethylaluminium (AlMe3).
- Velavan,Sumathi,Balasubramanian
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p. 5806 - 5815
(2014/10/16)
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- Synthesis of benzimidazoles by PIDA-promoted direct C(sp2)-H imidation of N-arylamidines
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A metal-free synthesis of diversified benzimidazoles from N-arylamidines through a phenyliodine(III) diacetate (PIDA) promoted intramolecular direct C(sp2)-H imidation has been developed. The reaction proceeds smoothly at 0 °C or ambient temperature to provide the desired products in good to excellent yields. The synthesis of 2-alkyl- or 2-alkyl-fused benzimidazoles, which are generally inaccessible by similar Pd- or Cu-catalyzed approaches, can also be achieved. Copyright
- Huang, Jinbo,He, Yimiao,Wang, Yong,Zhu, Qiang
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supporting information
p. 13964 - 13967
(2013/01/15)
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- Synthesis, characterization of bridged bis(amidinate) lanthanide amides and their application as catalysts for addition of amines to nitriles for monosubstituted N-arylamidines
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A series of lanthanide amide complexes supported by bridged bis(amidinate) ligand L, LLnNHAr1(DME) (L = [Me3SiNC(Ph)N(CH 2)3NC(Ph)NSiMe3], Ar1 = 2,6- iPr2C6
- Li, Wenbo,Xue, Mingqiang,Xu, Fan,Tu, Jing,Zhang, Yong,Shen, Qi
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supporting information; experimental part
p. 8252 - 8260
(2012/07/28)
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- Palladium-catalyzed intramolecular C(sp2)-H amidination by isonitrile insertion provides direct access to 4-aminoquinazolines from N-arylamidines
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An efficient method for the synthesis of 4-amino-2-aryl(alkyl)quinazolines from readily available N-arylamidines and isonitriles via palladium-catalyzed intramolecular aryl C-H amidination by isonitrile insertion has been developed.
- Wang, Yong,Wang, Honggen,Peng, Jiangling,Zhu, Qiang
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supporting information; experimental part
p. 4604 - 4607
(2011/10/12)
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- Ligand-free copper-catalyzed arylation of amidines
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Copper-catalyzed cross-coupling reactions of amidine salts were utilized to synthesize monoarylated amidines in moderate to high yields with ligand-free conditions. DMF was the superior solvent for the N-arylation of benzamidines, while MeCN was used in the formation of N-aryl amidines in moderate to high yield.(Figure Presented)
- Cortes-Salva, Michelle,Garvin, Corey,Antilla, Jon C.
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supporting information; experimental part
p. 1456 - 1459
(2011/04/26)
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- Reinvestigating the synthesis of N-arylbenzamidines from benzonitriles and anilines in the presence of AlCl3
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The preparation of N-phenylbenzamidine 3a from the reaction between benzonitrile Ia and aniline in the presence of AId3 is reinvestigated with respect to mode of reagent addition, reaction temperature and Lewis acid catalysis. Pre-forming the nitrile-Lewis acid complex prior to the addition of aniline allows for milder reaction conditions, allowing for the higher yielding synthesis of N-phenylbenzamidine 3a (83%). Using these modified conditions several N-(4-substituted phenyl)benzamidines can be prepared including the N-(4-methoxyphenyl)benzamidine 3b (93%) and the previously unobtainable 2-amino-N-(4-methoxyphenyl)benzamidine 31(56%). All new compounds are fully characterised.
- Koutentis, Panayiotis A.,Mirallai, Styliana I.
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experimental part
p. 5134 - 5139
(2010/08/20)
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- Synthesis and molecular structures of lanthanocene amide complexes and their catalytic activity for addition of amines to nitriles
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Reaction of (CH3C5H4)2LnCl(THF) with NaNHAr in a 1:1 molar ratio in THF afforded the amide complexes (CH3C5H4)2LnNHAr(THF) [(Ar = 2,6-Me2C6H
- Cai, Tao,Chen, Xiaoniu,Xu, Fan,Zhang, Yong,Yao, Yingming,Shen, Qi
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experimental part
p. 3167 - 3171
(2010/01/05)
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- Addition of amines to nitriles catalyzed by ytterbium amides: An efficient one-step synthesis of monosubstituted N-arylamidines
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A one-step synthesis of monosubstituted N-arylamidinates via addition of amines to nitriles catalyzed by ytterbium amides is reported. The reactions with various substrates give the products in good to excellent yields with 5 mol % ytterbium at 100 °C under solvent-free conditions.
- Wang, Junfeng,Xu, Fan,Cai, Tao,Shen, Qi
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p. 445 - 448
(2008/09/19)
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- Synthesis & Pharmacological Evaluation of Ethyl 3-Substituted-phenyl-2-methylmercapto/ phenyl/ methyl-4(3H)-pyrimidone-5-carboxylates
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A number of ethyl 3-substituted-phenyl-2-methylmercapto/ phenyl/ methyl-4(3H)-pyrimidone-5-carboxylates (V) have been prepared by the reaction of amidines (III) with diethyl ethoxymethylenemalonate.In order to confirm the structure (V), ethyl 3-(2'-methylphenyl)-2-methylmercapto-4(3H)pyrimidone-5-carboxylate (103) has been transformed into the earlier synthesised 3-(2'-methylphenyl)-2-methylmercapto-4(3H)-pyrimidone (115) by decarboxylation of 3-(2'-methylphenyl)-2-methylmercapto-4(3H)-pyrimidone-5-carboxylic acid (114), obtained by the alkaline hydrolysis of 103.Someof these compounds have shown antiinflammatory, diuretic and antipassive cutaneous anaphylaxis activities.
- Gupta, K. A.,Saxena, Anil K.,Jain, Padam C.
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p. 228 - 233
(2007/10/02)
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