Metal‐Free Synthesis of Pyrazoles from 1,3‐Diarylpropenes and Hydrazines <i>via</i> Multiple Inter‐/Intramolecular C–H Aminations

Tang, Li; Ma, Minyang; Zhang, Qi; Luo, Huan; Wang, Tao; Chai, Yonghai

doi:10.1002/adsc.201700196

Cited by 24 publications

(5 citation statements)

References 80 publications

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“…For examples, the transition-metal-catalyzed cross-coupling reactions, − [3+2] or [4+1] annulation using hydrazones, − annulation of azodicarboxylates with dipoles, electrophilic cyclization of functionalized hydrazones, − and annulation of diazo compounds , have been reported as effective methods. Despite the availability of these enriched synthetic pathways, the reaction of a hydrazine with a 1,3-electrophilic substrate such as 1,3-dicarbonyl substrates, − Michael acceptors, − tertiary enamines, and related multicomponent variants , remain as the predominant options. The advantages of such methods cover not only the stable and easily available substrates but also the fast generation of high molecular diversity from the varied reaction partners of hydrazines.…”

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confidence: 99%

Domino C-H Sulfonylation and Pyrazole Annulation for Fully Substituted Pyrazole Synthesis in Water Using Hydrophilic Enaminones

Guo

Wang

et al. 2019

J. Org. Chem.

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The cascade reactions between NH 2-functionalized enaminones and sulfonyl hydrazines have been developed for the synthesis of fully substituted pyrazoles. By making use of the hydrophilic primary amino group in the enaminones, the reactions proceed well in the medium of pure water in the presence of molecular iodine, TBHP, and NaHCO3 via cascade C-H sulfonylation and pyrazole annulation. The cleavage of the C–N bond in enaminones is confirmed by the experiment using 15 N-labeled enaminone.

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mentioning

confidence: 99%

Domino C-H Sulfonylation and Pyrazole Annulation for Fully Substituted Pyrazole Synthesis in Water Using Hydrophilic Enaminones

Guo

Wang

et al. 2019

J. Org. Chem.

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“…The reaction of trimellitic anhydride 21 with trimethylaniline 22 under acidic conditions yielded compound 25f [44]. Finally, condensation of 3,5-dimethylpyrazole 23 with ethyl bromoacetate 24, followed by hydrolysis with NaOH, yielded 25i [45]. Using 1-ethyl-3-(3-dimethylpropyl) carbodiimide (EDC)/1-hydroxybenzotriazole (HOBT) or 1-ethyl-3-(3-dimethylpropyl) base carbodiimide (EDC)/2-(7-azabenzotriazol-1-yl)-N, N, N', N'-tetramethyluronium hexafluorophosphate (HATU) as a condensing agent, benzenesulfonamide ( 9) condensed with various carboxylic acids (25), followed by deprotection of tetrahydropyran with saturated ammonium chloride solution, afforded the title compounds SW-(a-i), as shown in Scheme 2, and the overall yield was around 50%.…”

Section: Synthesismentioning

confidence: 99%

Design, Synthesis, Evaluation and Molecular Dynamics Simulation of Dengue Virus NS5-RdRp Inhibitors

Zong,

Li,

et al. 2023

Pharmaceuticals

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Dengue virus (DENV) is a major mosquito-borne human pathogen in tropical countries; however, there are currently no targeted antiviral treatments for DENV infection. Compounds 27 and 29 have been reported to be allosteric inhibitors of DENV RdRp with potent inhibitory effects. In this study, the structures of compounds 27 and 29 were optimized using computer-aided drug design (CADD) approaches. Nine novel compounds were synthesized based on rational considerations, including molecular docking scores, free energy of binding to receptor proteins, predicted Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) parameters, structural diversity, and feasibility of synthesis. Subsequently, the anti-DENV activity was assessed. In the cytopathic effect (CPE) assay conducted on BHK-21 cells using the DENV2 NGC strain, both SW-b and SW-d demonstrated comparable or superior activity against DENV2, with IC50 values of 3.58 ± 0.29 μM and 23.94 ± 1.00 μM, respectively, compared to that of compound 27 (IC50 = 19.67 ± 1.12 μM). Importantly, both SW-b and SW-d exhibited low cytotoxicity, with CC50 values of 24.65 μmol and 133.70 μmol, respectively, resulting in selectivity indices of 6.89 and 5.58, respectively. Furthermore, when compared to the positive control compound 3′-dATP (IC50 = 30.09 ± 8.26 μM), SW-b and SW-d displayed superior inhibitory activity in an enzyme inhibitory assay, with IC50 values of 11.54 ± 1.30 μM and 13.54 ± 0.32 μM, respectively. Molecular dynamics (MD) simulations elucidated the mode of action of SW-b and SW-d, highlighting their ability to enhance π–π packing interactions between benzene rings and residue W795 in the S1 fragment, compared to compounds 27 and 29. Although the transacylsulphonamide fragment reduced the interaction between T794 and NH, it augmented the interaction between R729 and T794. In summary, our study underscores the potential of SW-b and SW-d as allosteric inhibitors targeting the DENV NS5 RdRp domain. However, further in vivo studies are warranted to assess their pharmacology and toxicity profiles.

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“…[2] Among them, pyrazoles are of great interest, since they are considered as the privileged medicinal scaffold. [3] As a convenient route to substituted pyrazoles, oxidative intramolecular cyclizations of α,β-alkenyl hydrazones under the action of DDQ, [4] hypervalent iodine-based oxidants, [5] molecular iodine catalysis, [6] phosphotungstic acid/SiO 2 heterogenous catalysis [7] or under copper- [8] and vanadium-catalyzed [9] conditions were reported.…”

Section: Introductionmentioning

confidence: 99%

Electrocatalytic Synthesis of Substituted Pyrazoles via Hypervalent Iodine Mediated Intramolecular C−N Coupling

et al. 2022

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The electrochemical intramolecular cross‐dehydrogenative C(sp2)−H/N−H coupling of α,β‐unsaturated hydrazones resulting in substituted pyrazoles has been discovered. The process is catalyzed by hypervalent iodine species generated in situ through anodic oxidation of aryl iodide in fluorinated alcohol media. The formation of hypervalent iodine compound and its key role in the construction of a new C−N bond was confirmed with CV and NMR experiments. A wide range of substituted pyrazoles were obtained in yields ranging from 46% to 88%.

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Metal‐Free Synthesis of Pyrazoles from 1,3‐Diarylpropenes and Hydrazines via Multiple Inter‐/Intramolecular C–H Aminations

Cited by 24 publications

References 80 publications

Domino C-H Sulfonylation and Pyrazole Annulation for Fully Substituted Pyrazole Synthesis in Water Using Hydrophilic Enaminones

Domino C-H Sulfonylation and Pyrazole Annulation for Fully Substituted Pyrazole Synthesis in Water Using Hydrophilic Enaminones

Design, Synthesis, Evaluation and Molecular Dynamics Simulation of Dengue Virus NS5-RdRp Inhibitors

Electrocatalytic Synthesis of Substituted Pyrazoles via Hypervalent Iodine Mediated Intramolecular C−N Coupling

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