- Copper-Catalyzed Selective N-Arylation of Oxadiazolones by Diaryliodonium Salts
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Here, we report the method for copper-catalyzed N-arylation of diverse oxadiazolones by diaryliodonium salts under mild conditions in high yields (up to 92%) using available CuI as a catalyst. The developed method allows utilizing both symmetric and unsymmetric diaryliodonium salts bearing auxiliary groups such as 2,4,6-trimethoxyphenyl (TMP). We found that the steric effects in aryl moieties determined the chemoselectivity of N- and O-arylation of the 1,2,4-oxadiazol-5(4H)-ones. Mesityl-substituted diaryliodonium salts demonstrated the high potential as a selective arylation reagent. The structural study suggests that steric accessibility of N-atom in 1,2,4-oxadiazol-5(4H)-ones impact to arylation with sterically hindered diaryliodonium salts. The synthetic application of proposed method was also demonstrated on selective arylation of 1,3,4-oxadiazol-2(3H)-ones and 1,2,4-oxadiazole-5-thiol. (Figure presented.).
- Soldatova, Natalia S.,Semenov, Artem V.,Geyl, Kirill K.,Baykov, Sergey V.,Shetnev, Anton A.,Konstantinova, Anna S.,Korsakov, Mikhail M.,Yusubov, Mekhman S.,Postnikov, Pavel S.
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supporting information
p. 3566 - 3576
(2021/06/16)
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- Cobalt-Catalyzed, Directed Intermolecular C-H Bond Functionalization for Multiheteroatom Heterocycle Synthesis: The Case of Benzotriazine
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Transition-metal-catalyzed, directed intermolecular C-H bond functionalization is synthetically useful but heavily underexplored in multiheteroatom heterocycle synthesis. Herein we report a cobalt catalytic method for the formation of a three-nitrogen-bearing benzotriazine scaffold via the coupling of arylhydrazine and oxadiazolone. This synthetic protocol features a low-cost base metal catalyst, a maximum number of heteroatoms built into a heterocycle, a distinct synthetic logic for benzotriazines, a superior step economy, and a broad substrate scope.
- Wu, Weiping,Fan, Shuaixin,Li, Tielei,Fang, Lili,Chu, Benfa,Zhu, Jin
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p. 5652 - 5657
(2021/08/01)
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- COMPOUNDS
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A compound for use in the treatment of a disease ameliorated by the inhibition of Notum of formula (I): (I)
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Page/Page column 117
(2020/03/23)
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- 5-Phenyl-1,3,4-oxadiazol-2(3 H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit
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Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-Triazole 7 as an attractive starting point for a structure-based drug design hit-To-lead program. Optimization of 7 identified oxadiazol-2-one 23dd as a preferred example with properties consistent with drug-like chemical space. Screening 23dd in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of 23dd demonstrated good plasma exposure and partial blood-brain barrier penetration. Significant progress was made in developing fragment hit 7 into lead 23dd (>600-fold increase in activity), making it suitable as a new chemical tool for exploring the role of Notum-mediated regulation of Wnt signaling.
- Mahy, William,Willis, Nicky J.,Zhao, Yuguang,Woodward, Hannah L.,Svensson, Fredrik,Sipthorp, James,Vecchia, Luca,Ruza, Reinis R.,Hillier, James,Kj?r, Svend,Frew, Sarah,Monaghan, Amy,Bictash, Magda,Salinas, Patricia C.,Whiting, Paul,Vincent, Jean-Paul,Jones, E. Yvonne,Fish, Paul V.
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p. 12942 - 12956
(2020/11/13)
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- Tert-Butyl Nitrite Mediated Synthesis of 1,2,4-Oxadiazol-5(4 H)-ones from Terminal Aryl Alkenes
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tert-Butyl nitrite (TBN) mediated synthesis of 3-aryl-1,2,4-oxadiazol-5(4H)-ones has been accomplished using terminal aryl alkenes via a biradical reaction intermediate. Three consecutive sp2 C-H bond functionalizations of styrenes afforded 3-phenyl-1,2,4-oxadiazol-5(4H)-ones via the formation of new C?N, C?O, C-O, and two C-N bonds. Both of the N atoms originate from TBN, while the carbonyl oxygen is from the water (moisture) the other oxygen from the N?O part of the TBN.
- Sau, Prasenjit,Rakshit, Amitava,Alam, Tipu,Srivastava, Hemant Kumar,Patel, Bhisma K.
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supporting information
p. 4966 - 4970
(2019/07/03)
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- Rh(II)-Catalyzed Transannulation of 1,2,4-Oxadiazole Derivatives with 1-Sulfonyl-1,2,3-triazoles: Regioselective Synthesis of 5-Sulfonamidoimidazoles
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An effective method for the synthesis of fully substituted 5-sulfonamidoimidazoles by Rh(II)-catalyzed transannulation of 1,2,4-oxadiazole derivatives with N-sulfonyl-1,2,3-triazoles is reported. The reaction works well with both aromatic 1,2,4-oxadiazoles and 1,2,4-oxadiazol-5-ones providing a flexible approach to N-(alkoxy/amino)carbonyl- and N-alkyl-substituted imidazoles. Both the disclosed reactions are completely regioselective and provide the first examples of a carbenoid-mediated transformation of N,N,O-heterocycles.
- Strelnikova, Julia O.,Rostovskii, Nikolai V.,Starova, Galina L.,Khlebnikov, Alexander F.,Novikov, Mikhail S.
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p. 11232 - 11244
(2018/09/06)
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- Green synthesis method of oxadiazole derivatives
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The invention relates to the field of organic chemistry, overcomes disadvantages in the synthesis of oxadiazole derivatives in the prior art, and provides a green synthesis method of the oxadiazole derivatives. The method comprises the following specific steps: (1) adding a basic reagent, dropwise adding a carbonylation reagent, stirring evenly, and back-flowing at 100 DEG C, wherein water is usedas a solvent, N-hydroxybenzamidine or substituted N-hydroxybenzamidine is used as a raw material, the reaction time is 1-5 hours; and (2) after the reaction is finished, cooling, standing, adjustingpH to 3-4 with 1 mol/L diluted HCl acidification reaction solution, performing suction filtration, collecting filter cakes, washing the filter cakes with water, and performing vacuum drying to finallyobtain the oxadiazole derivative. N-hydroxybenzamidine or substituted N-hydroxybenzamidine and a carbonylation reagent are used as the raw materials, under the action of the basic reagent, the oxadiazole derivatives can be synthesized in one step in water, and the two steps of esterification and cyclization are simplified to one step, thus greatly shortening the reaction time and increasing the reaction yield. The method has the advantages of being mild in reaction conditions, convenient to separate and purify, green and environmentally friendly.
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Paragraph 0018-0019; 0035-0038
(2019/01/08)
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- Oxadiazolone-Enabled Synthesis of Primary Azaaromatic Amines
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Despite their tremendous synthetic and pharmaceutical utility, primary azaaromatic amines remain elusive for access based on a generally applicable C-H functionalization strategy. An oxadiazolone-enabled approach is reported for convenient entry into N-unsubstituted 1-aminoisoquinolines through Co(III)-catalyzed redox-neutral, step-, atom-, and purification-economic C-H functionalization with alkynes. A 15N labeling experiment reveals the effectiveness of both oxadiazolone N atoms as directing sites. The installed primary amine can be harnessed as a synthetically useful handle for attachment of divergent appendages.
- Yu, Xiaolong,Chen, Kehao,Yang, Fan,Zha, Shanke,Zhu, Jin
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p. 5412 - 5415
(2016/11/06)
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- OXADIAZOLE COMPOUNDS
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The present invention relates to a compound of formula (I) or (II) or a stereoisomer, enantiomer, racemic, or tautomer thereof, (I) (II) wherein R1,R2,R3,L1,L2,L3,L4,L5 and n, have the same meaning as that defined in the claims and the description. The present invention also relates to compositions, in particular pharmaceuticals, comprising such compounds, and to uses of such compounds and compositions for the prevention and/or treatment of metabolic disorders and/or neurodegenerative diseases, and/or protein misfolding disorders.
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Page/Page column 149
(2015/11/11)
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- NH-acidities and Hammett correlation of 3-para substituted phenyl-1,2,4-oxadiazol-5(4H)-ones and 1,2 λ43,5-oxathiadiazole 2-oxides in nonaqueous media
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NH acidities of some 3-(p-substitutedphenyl)-1,2,4-oxadiazol-5(4H)-ones and 4-(p-substitutedphenyl)-1,2 λ43,5-oxathiadiazole 2-oxides were determined in methanol by means of potentiometric titration with sodium methoxide. pKa values of the titl
- Dueruest, Nedime,Dueruest, Yasar,Goezlukaya, Emine Oezge
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- Kinetics of base-catalysed hydrolysis and cyclisation of substituted acetamide and benzamide O-(phenoxycarbonyl)oximes
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The reaction kinetics of acetamide O-(4-nitrophenoxycarbonyl)oxime have been studied in aqueous buffers at pH 2-11. At pH > 9, the pH dependence of kobs is linear with slope 1, the cyclisation to 3-methyl-1,2,4-oxadiazol-5(4H)-one and 4-nitrophenol being the only reaction. At pH obs on pH has been used to determine the rate equation and to propose the reaction mechanism. The cyclisation kinetics of substituted benzamide O-(phenoxycarbonyl)oximes have been studied in the pH range from 9.25 to 11. The reaction mechanism has been proposed based on the ρ constants found. In the first reaction step, the proton is split off from the NH2 group; the subsequent, rate-limiting step involves simultaneous N-C bond formation and C-O bond splitting.
- Mindl, Jaromir,Kavalek, Jaromir,Strakova, Helena,Sterba, Vojeslav
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p. 1641 - 1653
(2007/10/03)
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- New NO donors with antithrombotic and vasodilating activities, Part 26. Amidoximes and their prodrugs.
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Seventeen amidoximes (2a-q) comprising aliphatic (2a-d), aromatic (2e-n), and bis compounds (2o-q) have been synthesized. In the Born test 4-chlorophenylethenecarboxamidoxime (21) was most active and inhibited the blood platelet aggregation induced by col
- Rehse,Brehme
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p. 375 - 379
(2007/10/03)
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