- Photochemical Cyclopropenation of Alkynes with Diazirines as Carbene Precursors in Continuous Flow
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An efficient synthesis of 3-trifluoromethyl-3-aryl-cyclopropenes via the cyclopropenation reaction of alkynes with photolytically generated carbenes from diazirine compounds is described. This reaction is performed in continuous flow using readily available LEDs under mild reaction conditions. This new and efficient method describes the synthesis of 25 examples of 3-trifluoromethyl-3-aryl-cyclopropenes with yields up to 97%, achieved in continuous flow with a 5 min residence time. Control experiments highlighted that diazirines are more efficient than diazo compounds for this transformation.
- Tanbouza, Nour,Carreras, Virginie,Ollevier, Thierry
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supporting information
p. 5420 - 5424
(2021/07/26)
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- Photodecarboxylative Amination of Redox-Active Esters with Diazirines
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Diazirines have been recently demonstrated to serve as electrophilic amination reagents that afford diaziridines, versatile heterocycles that are readily transformed into amines, hydrazines, and nitrogen-containing heterocycles. Here, we report the photodecarboxylative amination of redox-active esters with diazirines using inexpensive photoactivators under mild conditions with an enhanced scope for primary substrates. The stability of diazirines to blue light is demonstrated, paving the way for further research into other photochemical amination methods with these unique heterocycles.
- Maharaj, Vishala,Chandrachud, Preeti P.,Che, Wen,Wojtas, Lukasz,Lopchuk, Justin M.
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supporting information
p. 8838 - 8842
(2021/11/24)
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- Decarboxylative Amination: Diazirines as Single and Double Electrophilic Nitrogen Transfer Reagents
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The ubiquity of nitrogen-containing small molecules in medicine necessitates the continued search for improved methods for C-N bond formation. Electrophilic amination often requires a disparate toolkit of reagents whose selection depends on the specific structure and functionality of the substrate to be aminated. Further, many of these reagents are challenging to handle, engage in undesired side reactions, and function only within a narrow scope. Here we report the use of diazirines as practical reagents for the decarboxylative amination of simple and complex redox-active esters. The diaziridines thus produced are readily diversifiable to amines, hydrazines, and nitrogen-containing heterocycles in one step. The reaction has also been applied in fluorous phase synthesis with a perfluorinated diazirine.
- Chandrachud, Preeti P.,Wojtas, Lukasz,Lopchuk, Justin M.
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p. 21743 - 21750
(2021/01/11)
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- Discovery of N-Cyano-sulfoximineurea Derivatives as Potent and Orally Bioavailable NLRP3 Inflammasome Inhibitors
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NLRP3 inflammasome mediated release of interleukin-1β (IL-1β) has been implicated in various diseases. In this study, rationally designed mimics of sulfonylurea moiety were investigated as NLRP3 inhibitors. Our results culminated into discovery of series of unprecedented N-cyano sulfoximineurea derivatives as potent NLRP3 inflammasome inhibitors. Compound 15 (IC50 = 7 nM) and analogues were found to be highly potent and selective NLRP3 inflammasome inhibitor with good pharmacokinetic profile. These effects translate in vivo, as 15, 29, and 34 significantly inhibit NLRP3 dependent IL-1β secretion in mice.
- Agarwal, Sameer,Sasane, Santosh,Shah, Hardik A.,Pethani, Jignesh P.,Deshmukh, Prashant,Vyas, Vismit,Iyer, Pravin,Bhavsar, Harsh,Viswanathan, Kasinath,Bandyopadhyay, Debdutta,Giri, Poonam,Mahapatra, Jogeswar,Chatterjee, Abhijit,Jain, Mukul R.,Sharma, Rajiv
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supporting information
p. 414 - 418
(2020/03/13)
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- PROCESSES AND COMPOUNDS FOR THE DECARBOXYLATIVE AMINATION OF REDOX-ACTIVE ESTERS WITH DIAZIRINES
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The invention described herein relates generally to processes for the synthesis of amine-containing organic compounds. More specifically, described herein relates to processes for the decarboxylative amination of redox-active esters with diazirines and the products formed thereof. Compounds for use in the above processes are also described.
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Page/Page column 20; 31
(2020/12/30)
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- SO2F2-Activated Efficient Beckmann Rearrangement of Ketoximes for Accessing Amides and Lactams
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A novel, mild and practical protocol for the efficient activation of the Beckmann rearrangement utilizing the readily available and economical sulfuryl fluoride (SO2F2 gas) has been developed. The substrate scope of the operationally simple methodology has been demonstrated by 37 examples with good to nearly quantitative isolated yields (over 90 % yield in most cases) in a short time, including B(OH)2, COOH, NH2, and OH substituted substrates. A tentative mechanism was proposed involving formation and elimination of key intermediate, sulfonyl ester.
- Zhang, Guofu,Zhao, Yiyong,Xuan, Lidi,Ding, Chengrong
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supporting information
p. 4911 - 4915
(2019/07/31)
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- Visible-Light-Photosensitized Aryl and Alkyl Decarboxylative Functionalization Reactions
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Despite significant progress in aliphatic decarboxylation, an efficient and general protocol for radical aromatic decarboxylation has lagged far behind. Herein, we describe a general strategy for rapid access to both aryl and alkyl radicals by photosensitized decarboxylation of the corresponding carboxylic acids esters followed by their successive use in divergent carbon–heteroatom and carbon–carbon bond-forming reactions. Identification of a suitable activator for carboxylic acids is the key to bypass a competing single-electron-transfer mechanism and “switch on” an energy-transfer-mediated homolysis of unsymmetrical σ-bonds for a concerted fragmentation/decarboxylation process.
- Patra, Tuhin,Mukherjee, Satobhisha,Ma, Jiajia,Strieth-Kalthoff, Felix,Glorius, Frank
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supporting information
p. 10514 - 10520
(2019/07/12)
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- Beckmann rearrangement of ketoxime catalyzed by N-methyl-imidazolium hydrosulfate
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Beckmann rearrangement of ketoxime catalyzed by acidic ionic liquid-N-methyl-imidazolium hydrosulfate was studied. Rearrangement of benzophenone oxime gave the desirable product with 45% yield at 90 ?C. When co-catalyst P2O5 was added, the yield could be improved to 91%. The catalyst could be reused three cycles with the same efficiency. Finally, reactions of other ketoximes were also investigated.
- Hu, Hongyu,Cai, Xuting,Xu, Zhuying,Yan, Xiaoyang,Zhao, Shengxian
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- Continuous Platform to Generate Nitroalkanes On-Demand (in Situ) Using Peracetic Acid-Mediated Oxidation in a PFA Pipes-in-Series Reactor
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The synthetic utility of the aza-Henry reaction can be diminished on scale by potential hazards associated with the use of peracid to prepare nitroalkane substrates and the nitroalkanes themselves. In response, a continuous and scalable chemistry platform to prepare aliphatic nitroalkanes on-demand using the oxidation of oximes with peracetic acid and direct reaction of the nitroalkane intermediate in an aza-Henry reaction is reported. A uniquely designed pipes-in-series plug-flow tube reactor addresses a range of process challenges, including stability and safe handling of peroxides and nitroalkanes. The subsequent continuous extraction generates a solution of purified nitroalkane, which can be directly used in the following enantioselective aza-Henry chemistry to furnish valuable chiral diamine precursors with high selectivity, thus completely avoiding isolation of the potentially unsafe low-molecular-weight nitroalkane intermediate. A continuous campaign (16 h) established that these conditions were effective in processing 100 g of the oxime and furnishing 1.4 L of nitroalkane solution.
- Tsukanov, Sergey V.,Johnson, Martin D.,May, Scott A.,Kolis, Stanley P.,Yates, Matthew H.,Johnston, Jeffrey N.
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supporting information
p. 971 - 977
(2018/08/28)
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- IDO inhibitors
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The invention discloses novel compounds used as indoleeamine-pyrrole-2,3-dioxygenase (IDO) inhibitors, and specifically discloses the compounds represented by a formula (I) shown in the description and pharmaceutically-acceptable salts of the compounds. The invention also discloses an application of the compounds represented by the formula (I) and the pharmaceutically-acceptable salts of the compounds in preparation of a medicament for treating tumors.
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Paragraph 0143; 0144; 0145
(2019/01/05)
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- Synthesis of diaziridines and diazirines via resin-bound sulfonyl oximes
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Diazirines are one of the most prominent functionalities in labeling experiments in vivo and in vitro because they allow photochemical generation of carbenes. The strategy presented herein describes the formation of diaziridines, being essential precursors in diazirine syntheses, using solid-supported procedures with immobilized sulfonyl oximes. The solid-supported building blocks have been shown to be valuable intermediates for CuAAC and amidation reactions, offering the possibility to build complex compounds with diverse functionalities.
- Protasova, Irina,Bulat, Bekir,Jung, Nicole,Br?se, Stefan
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supporting information
p. 34 - 37
(2017/11/28)
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- TETRAZOLINONE COMPOUND AND USE THEREOF
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The compound represented by formula (1): wherein R4 and R5 each represents a hydrogen atom, a halogen atom, or a C1-C3 alkyl group; R6 represents a C1-C4 alkyl group, a C3-C6 cycloalkyl group, or the like; R7, R8, and R9 each represents a hydrogen atom, a halogen atom, or the like; R10 represents a C1-C3 alkyl group, or the like; R13 represents a C1-C3 alkyl group, or the like; and Q represents a phenyl group, or the like; has an excellent control effect on pests.
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-
Paragraph 0844-0845
(2015/11/16)
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- Iron-Catalyzed C-N Bond Formation via the Beckmann Rearrangement
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A simple, iron-based catalytic system allows for facile Beckmann rearrangement of various oximes. The mild conditions avoid the use of harsh or expensive acids, and the reactions do not require an inert atmosphere. Additionally, a range of amides can be accessed through this transformation.
- Jefferies, Latisha R.,Weber, Savannah R.,Cook, Silas P.
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supporting information
p. 331 - 334
(2015/02/19)
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- Alternative one-pot synthesis of (trifluoromethyl)phenyldiazirines from tosyloxime derivatives: Application for new synthesis of optically pure diazirinylphenylalanines for photoaffinity labeling
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Alternative one-pot synthesis of 3-(trifluoromethyl)-3-phenyldiazirine derivatives from corresponding tosyloximes is developed. The deprotonation of intermediate diaziridine by NH2- is a new approach for construction of diazirine. Moreover, a novel synthesis of optically pure (trifluoromethyl)diazirinylphenylalanine derivatives was attempted involving these methods.
- Wang, Lei,Murai, Yuta,Yoshida, Takuma,Ishida, Akiko,Masuda, Katsuyoshi,Sakihama, Yasuko,Hashidoko, Yasuyuki,Hatanaka, Yasumaru,Hashimoto, Makoto
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supporting information
p. 616 - 619
(2015/03/04)
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- Economical and practical strategies for synthesis of α-trifluoromethylated amines
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A powerful approach to synthesize α-trifluoromethylated amines has been developed. The method is operationally simple, broad in substrate scope and amenable to scale-up using trifluoroacetic anhydride. Meanwhile, the strategy not only provided a versatile approach to synthesize α-trifluoromethylated amines but also provides a new method for exploring the new reactivity of trifluoroacetic anhydride.
- Jiang,Cheng,Yuan
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p. 2406 - 2408
(2016/05/19)
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- Structure-activity study leading to identification of a highly active thienopyrimidine based EGFR inhibitor
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Based on the thieno[2,3-d]pyrimidine scaffold, a series of new 4-amino-6-aryl thienopyrimidines have been prepared and evaluated as EGFR tyrosine kinase inhibitors. The in vitro activity was found to depend strongly on the substitution pattern in the 6-aryl ring, the stereochemistry, and the basicity at the secondary 4-amino group. A stepwise optimization by combination of active fragments led to the discovery of three structures with EGFR IC 50 50 of 0.3 nM towards EGFR and its mutants L858R and L861Q. Studies using human cancer cell lines and an EGFR-L858R reporter cell system revealed good cellular potency, verifying the identified thienopyrimidines as promising lead structures.
- Bugge, Steffen,Kaspersen, Svein Jacob,Larsen, Synne,Nonstad, Unni,Bj?rk?y, Geir,Sundby, Eirik,Hoff, B?rd Helge
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p. 354 - 374
(2014/03/21)
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- PYRROLO [3, 2 -E] [1,2,4] TRIAZOLO [1,5 -A] PYRIMIDINES DERIVATIVES AS INHIBITORS OF MICROGLIA ACTIVATION
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The invention relates to novel compounds useful in the treatment and prophylaxis of disease. Compounds of the formula (I) wherein X is halogen, independently selected form chlorine and fluorine and n is 0, 1 or 2. and their pharmaceutically acceptable salts are useful in the treatment and prophylaxis of diseases caused by activation of microglia, particularly Alzheimer's disease.
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Page/Page column 15
(2011/04/26)
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- COSMETIC USE OF AND COSMETIC COMPOUND CONTAINING PHOTOREACTIVE COMPOUND, PHOTOREACTIVE POLYAMINE AND POLYAMINE SHEET
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A use of a polyamine sheet usable for cosmetic purposes is disclosed. A photoreactive polyamine utilized for the creation of this polyamine sheet, and a photoreactive compound that comprises a raw material for this photoreactive polyamine is also disclosed as well as their use for cosmetic purposes and cosmetic compounds containing the same. A photoreactive compound having a diazirine group as a photoreactive group, a photoreactive polyamine compound created from this photoreactive compound and polyamine, a polyamine sheet utilizing this photoreactive polyamine compound, and production methods thereof are disclosed along with their cosmetic uses and cosmetic compounds containing the same.
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Page/Page column 13-14
(2008/06/13)
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- THIADIAZOLES AS CXC- AND CC- CHEMOKINE RECEPTOR LIGANDS
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Disclosed are novel compounds of Formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and ischemia reperfusion injury, pain (e.g., acute pain, acute and chronic inflammatory pain, and neuropathic pain) using a compound of Formula (IA).
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Page/Page column 208
(2010/02/12)
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- 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
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There are disclosed compounds of the formula or a pharmaceutically acceptable salt or solvate thereof which are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.
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- 3,4-Di-substituted cyclobutene-1,2-diones as CXC-chemokine receptor ligands
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There are disclosed compounds of the formula or a pharmaceutically acceptable salt or solvate thereof which are useful for the treatment of chemokine-mediated diseases such as acute and chronic inflammatory disorders and cancer.
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- Enantiomeric excess determination of α-amino acids by 19F NMR spectroscopy of their N,N-dimethyl-(2,2,2-trifluoro-1-phenylethyl)amine-C,N)palladium complexes
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The synthesis and resolution of the trifluoromethyl-palladacycle, di-μ-chloro-bis(N,N-dimethyl-(2,2,2-trifluoro-1-phenylethyl)amine-2-C,N) palladium(II) are shown. The utility of the complex and its application in the enantiomeric excess determination of α-amino acids by 19F NMR spectroscopy is demonstrated and X-ray diffraction analysis of one of the diastereomeric complexes, trans-{[(R)-phenylglycinato-N,O][(R)-N,N-dimethyl-(2,2,2-trifluoro-1- phenylethyl)amine-C,N]palladium(II)}, is reported.
- Levrat, Fabrice,Stoeckli-Evans, Helen,Engel, Norbert
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p. 2335 - 2344
(2007/10/03)
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- 19F NMR non-equivalence of diastereomeric amides of 2,2,2-trifluoro-1-phenylethylamine
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An alternate synthesis and resolution is reported for 2,2,2-trifluoro-1-phenylethylamine. The 19F NMR of a series of amide derivatives of chiral acids is described. The diastereomeric non-equivalence of the 19F NMR signals (0.05-0.09 ppm) of these amides permits use of these derivatives for determination of enantiomeric purity of alpha-substituted acids. The potential for configurational correlations is discussed.
- Wang,Mosher
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p. 987 - 990
(2007/10/02)
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