- Cu-Catalyzed Oxidative-Reaction of Tosylmethylisocyanide and Benzyl Alcohols: Efficient Synthesis of 4-(tert-butylperoxy)-5-aryloxazol-2(3H)-ones and 5-Aryloxazol-2(5H)-ones
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Herein, a novel copper-catalyzed reaction of tosylmethylisocyanide (TosMIC) with benzyl alcohols has been developed using tert-butyl hydroperoxide (TBHP) for the first time. The reaction involves the in-situ oxidation of benzyl alcohol to corresponding be
- Sepahvand, Heshmatollah,Bazgir, Ayoob,Shaabani, Ahmad
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- A new efficient synthesis of 5-aryloxazoles from arylidene diacetates and application to the preparation of BMS-337197, a novel IMPDH inhibitor
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A new method for the synthesis of 5-aryloxazoles is described. Treatment of arylidene diacetates with one equivalent of TosMIC reagent in the presence of excess of potassium carbonate in methanol afforded 5-aryloxazoles in "one-pot" in 90-94%. Heteroaryli
- Chen, Bang-Chi,Bednarz, Mark S.,Zhang, Huiping,Zhao, Rulin,Murali,Balu Balasubramanian, Dhar,Barrish, Joel C.
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- Discovery of a Potent Glutathione Peroxidase 4 Inhibitor as a Selective Ferroptosis Inducer
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Potent and selective ferroptosis regulators promote an intensive understanding of the regulation and mechanisms underlying ferroptosis, which is highly associated with various diseases. In this study, through a stepwise structure optimization, a potent and selective ferroptosis inducer was developed targeting to inhibit glutathione peroxidase 4 (GPX4), and the structure-activity relationship (SAR) of these compounds was uncovered. Compound26aexhibited outstanding GPX4 inhibitory activity with a percent inhibition up to 71.7% at 1.0 μM compared to 45.9% of RSL-3. At the cellular level,26acould significantly induce lipid peroxide (LPO) increase and effectively induce ferroptosis with satisfactory selectivity (the value of 31.5). The morphological analysis confirmed the ferroptosis induced by26a. Furthermore,26asignificantly restrained tumor growth in a mouse 4T1 xenograft model without obvious toxicity.
- Xu, Congjun,Xiao, Zhanghong,Wang, Jing,Lai, Hualu,Zhang, Tao,Guan, Zilin,Xia, Meng,Chen, Meixu,Ren, Lingling,He, Yuanfeng,Gao, Yuqi,Zhao, Chunshun
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p. 13312 - 13326
(2021/09/28)
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- Design, synthesis and biological evaluation of imidazole and oxazole fragments as HIV-1 integrase-LEDGF/p75 disruptors and inhibitors of microbial pathogens
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We describe here the synthesis of libraries of novel 1-subtituted-5-aryl-1H-imidazole, 5-aryl-4-tosyl-4,5-dihydro-1,3-oxazole and 5-aryl-1,3-oxazole fragments via microwave (MW)-assisted cycloaddition of para-toluenesulfonylmethyl isocyanide (TosMIC) to imines and aldehydes. The compounds obtained were biologically evaluated in an AlphaScreen HIV-1 IN-LEDGF/p75 inhibition assay with six imidazole-based compounds (16c, 16f, 17c, 17f, 20a and 20d) displaying more than 50% inhibition at 10 μM, with IC50 values ranging from 7.0 to 30.4 μM. Additionally the hypothesis model developed predicts all active scaffolds except 20d to occupy similar areas as the N-heterocyclic (A) moiety and two aromatic rings (B and C) of previously identified inhibitor 5. These results indicate that the identified compounds represent a viable starting point for their use as templates in the design of next generation inhibitors targeting the HIV-1 IN and LEDGF/p75 protein-protein interaction. In addition, the in vitro antimicrobial properties of these fragments were tested by minimum inhibitory concentration (MIC) assays showing that compound 16f exhibited a MIC value of 15.6 μg/ml against S. aureus, while 17f displayed a similar MIC value against B. cereus, suggesting that these compounds could be further developed to specifically target those microbial pathogens.
- Rashamuse, Thompho J.,Harrison, Angela T.,Mosebi, Salerwe,van Vuuren, Sandy,Coyanis, E. Mabel,Bode, Moira L.
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- Reaction Conditions for the Regiodivergent Direct Arylations at C2- or C5-Positions of Oxazoles using Phosphine-Free Palladium Catalysts
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Two sets of reaction conditions for the regiodivergent C2- or C5- direct arylations of oxazole are reported. In both cases, phosphine-free catalysts and inexpensive bases were employed allowing the access to the arylated oxazoles in moderate to high yields. Using Pd(OAc)2/KOAc as catalyst and base, regioselective C5-arylations were observed; whereas, using Pd(acac)2/Cs2CO3 system, the arylation occurred at the C2-position of oxazole. The higher reactivity of C5-H bond of oxazole as compared to the C2-H bond in the presence of Pd(OAc)2/KOAc system is consistent with a concerted metalation deprotonation mechanism; whereas the C2-arylation likely occurs via a simple base deprotonation of the oxazole C2-position. Then, from these C2- or C5-arylated oxazoles, a second palladium-catalyzed direct C?H bond arylation affords 2,5-diaryloxazoles with two different aryl groups. We also applied these sequential arylations to the straightforward synthesis of 2-arylphenanthro[9,10-d]oxazoles via three C?H bond functionalization steps. The Ru-catalyzed C?H arylation of the aryl unit of 2-aryloxazoles is also described. (Figure presented.).
- Shi, Xinzhe,Soulé, Jean-Fran?ois,Doucet, Henri
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p. 4748 - 4760
(2019/09/12)
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- Tandem oxidative isocyanide-based cycloaddition reactions in the presence of MIL-101(Cr) as a reusable solid catalyst
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The tandem oxidative three-component synthesis of two types of the heterocycles such as furans and imidazopyridines, via isocyanides [1+4] cycloaddition reactions in the presence of MIL-101(Cr) under aerobic conditions are reported. When the 4-toluenesulfonylmethyl isocyanide was used, an unexpected [3+2] cycloaddition reaction of isocyanides with aldehydes accomplished and dihydrophenyloxazoles and phenyloxazoles produced. These syntheses were successfully carried out using a wide scope of the substrates.
- Shaabani, Ahmad,Sepahvand, Heshmatollah,Amini, Mostafa M.,Hashemzadeh, Alireza,Borjian Boroujeni, Mahmoud,Badali, Elham
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p. 1832 - 1837
(2018/03/07)
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- Tandem cycloaddition-decarboxylation of α-keto acid and isocyanide under oxidant-free conditions towards monosubstituted oxazoles
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An efficient method, tandem [3 + 2] cycloaddition-decarboxylation of α-keto acid and isocyanide promoted by copper salt, has been developed. Under oxidant-free conditions, a series monosubstituted oxazoles have been constructed. Different from the traditional application of α-oxo acids as acyl surrogates, the elegant approach herein ingeniously avoids consuming excess oxidants.
- Zhang, Ling-Juan,Xu, Mei-Chen,Liu, Jie,Zhang, Xian-Ming
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p. 73450 - 73453
(2016/08/18)
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- A One-Pot Tandem Approach for the Synthesis of 5-(Het)aryloxazoles from Substituted (Het)aryl Methyl Alcohols and Benzyl Bromides
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A new modified van Leusen strategy has been developed for the synthesis of biologically significant 5-substituted oxazoles by the reaction of (het)aryl methyl alcohols or benzyl bromides as precursors with tosylmethylisocyanide (TosMIC) under basic conditions. This method is efficient, takes place under mild reaction conditions, and is tolerant of various functional groups with high yield.
- Vinay Kumar, Koravangala S.,Swaroop, Toreshettahally R.,Rajeev, Narasimhamurthy,Vinayaka, Ajjampura C.,Lingaraju, Gejjalagere S.,Rangappa, Kanchugarakoppal S.,Sadashiva, Maralinganadoddi P.
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supporting information
p. 1363 - 1366
(2016/06/01)
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- Mild palladium-catalyzed regioselective direct arylation of azoles promoted by tetrabutylammonium acetate
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A mild, general, and convenient palladium-catalyzed direct arylation of the 5-position of azoles with aryl bromides, efficiently promoted by tetrabutylammonium acetate, is described. 1-Methylpyrazole, oxazole, and thiazole reacted at 70°C in N,N-dimethyla
- Bellina, Fabio,Lessi, Marco,Manzini, Chiara
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p. 5621 - 5630
(2013/09/12)
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- Copper-mediated C-H/C-H biaryl coupling of benzoic acid derivatives and 1,3-azoles
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Hot couple: A precious-metal-free copper-mediated intermolecular direct biaryl coupling of benzoic acid derivatives and 1,3-azoles has been developed. The key to success is the installation of an amide-based bidentate coordinating group, which is easily removed and transformed into the parent ester groups after the coupling reaction. Kinetic studies indicate that the rate-limiting step is the aromatic C-H bond cleavage of benzoic acid derivatives. Copyright
- Nishino, Mayuko,Hirano, Koji,Satoh, Tetsuya,Miura, Masahiro
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supporting information
p. 4457 - 4461
(2013/05/22)
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- Copper-mediated dehydrogenative biaryl coupling of naphthylamines and 1,3-azoles
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A copper-mediated dehydrogenative biaryl cross-coupling of naphthylamines and 1,3-azoles has been developed. The key to its success is the introduction of N,N-bidentate coordination system based on the picolinamide directing group. The reaction proceeds s
- Odani, Riko,Hirano, Koji,Satoh, Tetsuya,Miura, Masahiro
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p. 11045 - 11052
(2013/11/19)
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- Copper-mediated and copper-catalyzed cross-coupling of indoles and 1,3-azoles: Double C-H activation
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A new bronze age: The described copper-mediated cross-coupling with double C-H activation can provide a convergent access to indole-containing biheteroaryls that are of high interest in pharmaceutical and medicinal chemistry. In this strategy an easily attachable and detachable 2-pyrimidyl directing group is used. Moreover, a variant that is catalytic in copper is achieved by using atmospheric oxygen as an ideal co-oxidant (see scheme). Copyright
- Nishino, Mayuko,Hirano, Koji,Satoh, Tetsuya,Miura, Masahiro
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supporting information; experimental part
p. 6993 - 6997
(2012/10/07)
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- 1,1-dibromo-1-alkenes as valuable partners in the copper-catalyzed direct alkynylation of azoles
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The copper-catalyzed direct alkynylation of azoles with 1,1-dibromo-1-alkenes as electrophiles is described. These easily accessible substrates are a useful addition to the field of direct alkynylations in an efficient and functional group tolerant reaction to provide a straightforward entry to diverse alkynyl heterocycles.
- Pacheco Berciano, Beatriz,Lebrequier, Sabrina,Besselievre, Francois,Piguel, Sandrine
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supporting information; experimental part
p. 4038 - 4041
(2010/11/16)
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- A Mild and convenient synthesis of 4-tosyl-4,5-dihydrooxazoles
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A facile and mild synthesis of 4-tosyl-4,5-dihydrooxazoles is described. The reaction between tosyl methyl isocyanide (TosMIC) and cinnamic or aromatic aldehydes is catalyzed by triethylamine, affording trans-5-styryl- or 5-aryl-4-tosyl-4,5-dihydrooxazole
- Companyo, Xavier,Moyano, Albert,Rios, Ramon
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experimental part
p. 293 - 296
(2010/04/23)
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- Heterocyclizations via TosMIC-based multicomponent reactions: A new approach to one-pot facile synthesis of substituted quinoxaline derivatives
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A novel multicomponent reaction involving o-phenylenediamines, aldehydes and p-toluenesulfonylmethyl isocyanide (TosMIC) in the presence of a base leading to the formation of quinoxalines in very good yields is described. Georg Thieme Verlag Stuttgart.
- Neochoritis, Constantinos,Stephanidou-Stephanatou, Julia,Tsoleridis, Constantinos A.
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scheme or table
p. 302 - 305
(2009/06/23)
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- Reactions between weinreb amides and 2-magnesiated oxazoles: A simple and efficient preparation of 2-acyl oxazoles
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(Chemical Equation Presented) Treatment of oxazole or 5-aryl oxazoles with i-PrMgCl smoothly generates the corresponding 2-Grignard reagents, which react with Weinreb amides to provide exclusively 2-acyl oxazole products.
- Pippel, Daniel J.,Mapes, Christopher M.,Mani, Neelakandha S.
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p. 5828 - 5831
(2008/02/09)
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- ANTIFUNGAL AGENTS
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Compounds of formula (I), and pharmaceutically acceptable salts thereof, may be used in therapy, for example as antifungal agents: (I) wherein: Rl, R2, R3, R4, R5, R6, R7, X and X1 are as defined herein. Certain compounds of formula (I) are also provided. Compounds of formula (T), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
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Page/Page column 66
(2008/06/13)
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- Pyrimidines and uses thereof
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The invention relates to pyrimidines and uses thereof, including to inhibit lysophosphatidic acid acyltransferase β (LPAAT-β) activity and/or proliferation of cells such as tumor-cells.
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- PROCESS FOR PRODUCING 5-SUBSTITUTED OXAZOLE COMPOUNDS AND 5-SUBSTITUTED IMIDAZOLE COMPOUNDS
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A process for producing heterocyclic compounds which are useful as pesticides, drugs, functional materials or intermediates thereof. TosMIC is reacted with an aldehyde or an imino compound (1) in a solvent mixture of an aprotic solvent with a protic solve
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- NOVEL AMIDE COMPOUNDS
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A compound of the formula (I):R1-A-X-NHCO-Y-R2 ???whereinR1 is heterocyclic group which may have suitable substituents, or phenyl which may have suitable substituents,R2 is condensed phenyl which may have suitable substituents, phenyl which may have suitable substituents, or thienyl which may have suitable substituents,A is a group of the formula:-(CH2)t-(O)m- or in which R3 and R4 are each hydrogen or linked together to form imino,R5 is hydrogen or lower alkyl,t is 0, 1 or 2,p, m and n are each 0 or 1,X is phenylene which may have suitable substituents, or bivalent heterocyclic group containing nitrogen which may have suitable substituents,Y is bond, lower alkylene, or lower alkenylene, and a salt thereof.
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- Oxazole synthesis with minimal purification: Synthesis and application of a ROMPgel tosmic reagent
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equations presented The synthesis of ring opening metathesis, polymer-supported Tosmic reagent 1 is described. This reagent was utilized in the conversion of aldehydes to oxazoles in good yields and purities.
- Barrett, Anthony G. M.,Cramp, Susan M.,Hennessy, Alan J.,Procopiou, Panayiotis A.,Roberts, Richard S.
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p. 271 - 273
(2007/10/03)
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- A solid-phase equivalent of van Leusen's TosMIC, and its application in oxazole synthesis
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Polystyrene-SH resin, prepared from Merrifield resin in two steps, was converted to polystyrene-SO2-CH2-NC in three steps. This resin functions as a solid-phase equivalent of p-tolylsulfonylmethyl isocyanide (TosMIC). Thus, reaction with aromatic aldehydes and tetrabutylammonium hydroxide as base yields 5-aryloxazoles.
- Kulkarni, Bheemashankar A.,Ganesan
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p. 5633 - 5636
(2007/10/03)
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- Solution-phase parallel oxazole synthesis with TosMIC
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A quaternary ammonium hydroxide ion exchange resin catalyzes the reaction of p-tolylsulfonylmethyl isocyanide (TosMIC) with aromatic aldehydes to give 5-aryloxazoles. The base and the p-tolylsulfinic acid byproduct are removed by simple filtration, result
- Kulkarni, Bheemashankar A.,Ganesan
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p. 5637 - 5638
(2007/10/03)
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