- Method for preparing hydrofluoroether through two-step process
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The invention discloses a method for preparing hydrofluoroether through a two-step process. With the method provided by the invention, p-toluensulfonyl chloride and fluorine-containing alcohol are subjected to a reaction to obtain p-toluenesulfonate, and the p-toluenesulfonate and sodium alkoxide are subjected to a Williamson ether synthetic reaction to obtain the hydrofluoroether. The method disclosed by the invention has the advantages of cheap and low-toxicity raw materials, mild and controllable reaction conditions, and high yield.
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Paragraph 0061; 0062; 0073; 0074
(2019/07/10)
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- Discovery of a class of highly potent Janus Kinase 1/2 (JAK1/2) inhibitors demonstrating effective cell-based blockade of IL-13 signaling
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Disruption of interleukin-13 (IL-13) signaling with large molecule antibody therapies has shown promise in diseases of allergic inflammation. Given that IL-13 recruits several members of the Janus Kinase family (JAK1, JAK2, and TYK2) to its receptor complex, JAK inhibition may offer an alternate small molecule approach to disrupting IL-13 signaling. Herein we demonstrate that JAK1 is likely the isoform most important to IL-13 signaling. Structure-based design was then used to improve the JAK1 potency of a series of previously reported JAK2 inhibitors. The ability to impede IL-13 signaling was thereby significantly improved, with the best compounds exhibiting single digit nM IC50’s in cell-based assays dependent upon IL-13 signaling. Appropriate substitution was further found to influence inhibition of a key off-target, LRRK2. Finally, the most potent compounds were found to be metabolically labile, which makes them ideal scaffolds for further development as topical agents for IL-13 mediated diseases of the lungs and skin (for example asthma and atopic dermatitis, respectively).
- Zak, Mark,Hanan, Emily J.,Lupardus, Patrick,Brown, David G.,Robinson, Colin,Siu, Michael,Lyssikatos, Joseph P.,Romero, F. Anthony,Zhao, Guiling,Kellar, Terry,Mendonca, Rohan,Ray, Nicholas C.,Goodacre, Simon C.,Crackett, Peter H.,McLean, Neville,Hurley, Christopher A.,Yuen, Po-wai,Cheng, Yun-Xing,Liu, Xiongcai,Liimatta, Marya,Kohli, Pawan Bir,Nonomiya, Jim,Salmon, Gary,Buckley, Gerry,Lloyd, Julia,Gibbons, Paul,Ghilardi, Nico,Kenny, Jane R.,Johnson, Adam
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supporting information
p. 1522 - 1531
(2019/04/25)
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- Anti-artz sea silent sickness drug Lu - AE - 58054 preparation method (by machine translation)
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The invention discloses a novel method for preparing a medicine Lu-AE-58054 for resisting an alzheimer's disease. The novel method comprises the following steps: firstly, reacting 2,2,3,3-tetrafluoromethane-1-propyl alcohol with paratoluensulfonyl chlorid
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Paragraph 0080; 0081
(2019/01/22)
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- Synthesis and physical properties of new fluoroether sulfones
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Eight new strategically designed fluoroether sulfone solvents have been synthesized through different synthetic pathways for potential applications in lithium-sulfur battery electrolytes. The structures of these compounds have been confirmed by 1H-NMR, 13C-NMR and elemental analysis. Several 1,2-dimethoxyethane (DME)-based electrolyte formulations have been prepared with these solvents to derive an electrolyte with good ionic conductivity (>5 mS cm?1 at 25 ℃). The viscosity of these new additives has also been determined as it is directly related to the ionic conductivity. Three of these solvents that contain a trifluoromethyl group displayed acceptable ionic conductivity.
- Yue, Zheng,Mei, Xinyi,Dunya, Hamza,Ma, Qiang,McGarry, Christopher,Mandal, Braja K.
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p. 118 - 123
(2018/11/10)
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- PROCESS FOR THE MANUFACTURE OF IDALOPIRDINE
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Disclosed herein is a process for the preparation of idalopirdine and pharmaceutically acceptable salts thereof.
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Paragraph 0099; 0100
(2016/07/05)
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- Alternative synthetic routes to hydrofluoroolefins
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A series of hydrofluoroolefins with -CF=CH2, -CH=CHF and -CH=CF2 groups were designed and prepared via various synthetic routes, including HX or BrF elimination, Wittig-type olefination or fluorination using SF4.
- Yagupolskii, Yu. L.,Pavlenko,Shelyazhenko,Filatov,Kremlev,Mushta,Gerus,Peng, Sheng,Petrov,Nappa, Mario
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p. 134 - 141
(2015/11/10)
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- Highly stereoselective approach to 3-fluoroalkylated (E)-hex-3-ene-1,5- diyne derivatives via an addition-elimination reaction
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Palladium(0)-catalyzed Sonogashira cross-coupling reaction of 2-fluoroalkylated (Z)-2-fluoro-1-iodoethene, which is easily prepared from commercially available polyfluorinated alcohols in facile three steps, with terminal alkynes in DMF at room temperature for 24 h took place stereospecifically to give the corresponding 1-fluoroalkylated (Z)-1-fluorobut-1-en-3-yne derivatives in good to excellent yield. Thus obtained fluoroalkylated 1-fluoroenynes were effectively subjected to addition-elimination reaction with various alkynyllithiums at room temperature, leading to 3-fluoroalkylated hex-3-ene-1,5-diyne derivatives in good to high yields with an excellent E selectivity.
- Konno, Tsutomu,Kishi, Misato,Ishihara, Takashi,Yamada, Shigeyuki
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p. 144 - 151
(2013/11/19)
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- 2-AMINO PYRIMIDINE COMPOUNDS AS POTENT HSP-90 INHIBITORS
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The present invention is directed to compounds of formula (I), or pharmaceutically acceptable salts thereof, their synthesis, and their use as HSP-90 inhibitors.
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Page/Page column 26
(2010/03/04)
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- Ionic liquids on the basis of 2,3,4,6,7,8,9,10-octahydropyrimido-[1,2-a] azepine (1,8-diazabicyclo[5.4.0]undec-7-ene)
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New ionic liquids containing alkyl and polyfluoroalkyl substituents and various anions were synthesized from 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a] azepinium ion (1,8-diazabicyclo[5.4.0]undec-7-en-8-ium). Their NMR spectra and miscibility with water and organic solvents were studied. Pleiades Publishing, Inc., 2006.
- Tolstikova,Shainyan
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p. 1068 - 1074
(2007/10/03)
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- Facile syntheses of various per- or polyfluoroalkylated internal acetylene derivatives
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Treatment of per- or polyfluoroalkylated vinyl iodides 5 with 2equiv. of n-BuLi in THF produced the corresponding lithium acetylides in situ, which were transformed into zinc acetylides by the addition of ZnCl2· TMEDA complex into the reaction mixture. The in situ generated zinc acetylides were exposed to the cross-coupling conditions such as ArI/cat. Pd(PPh 3)4, reflux, 6-12 h, giving rise to the desired per- or polyfluoroalkylated acetylenes in high yields. In the case of trifluoromethylated acetylene, commercially available 2-bromo-3,3,3-trifluoropropene 6 could also be used instead of 5 as the starting material. In the acetylenes having a fluoroalkyl group and an aliphatic side chain, vinyl iodides 7, prepared by radical addition of perfluoroalkyl iodide to terminal acetylenes, were treated with t-BuOK at room temperature or at the reflux temperature of benzene, affording the desired compounds in good yields.
- Konno, Tsutomu,Chae, Jungha,Kanda, Masashi,Nagai, Go,Tamura, Kazushige,Ishihara, Takashi,Yamanaka, Hiroki
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p. 7571 - 7580
(2007/10/03)
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- Inorganic anionic oxygen-containing α-nucleophiles - Effective acyl group acceptors: Hydroxylamine ranks first among the α-nucleophile series
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Comparative analysis of the nucleophilicity of inorganic oxygen-containing α-nucleophiles (hydroxylamine and ClO-, BrO--, HOO--, NH2O-, and F- ions) covering the pKa range from -2 to 13.81 toward 4-nitrophenyl esters (4-nitrophenyl acetate, 4-nitrophenyl p-toluenesulfonate, diethyl 4-nitrophenyl phosphate, ethyl 4-nitrophenyl ethylphosphonate, and 4-nitrophenyl dimethylcarbamate) in water at 25°C (ionic strength μ 1.0, KCl) was performed in terms of the extrathermodynamic Brosted relation. It was found for the first time that hydroxylamine anion ranks first among the series of α-nucleophiles. It is more reactive than HOO- ion with respect to 4-nitrophenyl acetate (by a factor of ~8), 4-nitrophenyl p-toluenesulfonate (by a factor of ~4) and 4-nitrophenyl dimethylcarbamate (by a factor of ~10). The nucleophilicities of HOO- and NH 2O- ions toward diethyl 4-nitrophenyl phosphate and ethyl 4-nitrophenyl ethylphosphonate are comparable. Taking into account that neutral hydroxylamine exhibits an anomalously high reactivity, as compared to not only common organic but also inorganic α-nucleophiles, it may be regarded as a unique α-nucleophile. Both neutral hydroxylamine and its anion as O-nucleophiles ensure high rates of acyl group transfer throughout a wide range of pH.
- Simanenko,Popov,Prokop'eva,Karpichev,Savelova,Suprun,Bunton
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p. 1286 - 1298
(2007/10/03)
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- Facile generation of polyfluoro-1-(tosyloxy)prop-1-enyllithiums and their reaction with electrophiles. A new, efficient and convenient access to (Z)-1,1-di- and 1,1,1-tri-fluoro-3-(tosyloxy)alk-3-en-2-ones
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Polyfluoro-1-(tosyloxy)prop-1-enyllithiums, generated by the reaction of polyfluoropropyl toluene-p-sulfonates or polyfluoroprop-1-enyl toluene-p-sulfonates with n-butyllithium, readily react with a variety of electrophiles, such as aldehydes, ketones, me
- Funabiki, Kazumasa,Ohtsuki, Tetsuya,Ishihara, Takashi,Yamanaka, Hiroki
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p. 2413 - 2423
(2007/10/03)
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- 19F nuclear magnetic resonance studies of halogenated propanes
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The relationship between 19F chemical shifts in halogenated propanes and their structures are elucidated using MNDO calculations to determine the population of rotamers.The pairs of atom gauche to a fluorine atom and van der Waals interaction between the two terminal substituents are responsible for the 19F chemical shifts.The differences among chemical shifts in diastereomers are also discussed in terms of the conformation of molecule.
- Tanuma, T.,Ohnishi, K.,Okamoto, H.,Miyajima, T.,Morikawa, S.
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p. 259 - 284
(2007/10/02)
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- α,α,ω-TRIHYDRO-α-HALOPERFLUOROALKANES
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A synthesis has been developed for α,α,ω-trihydrohaloperfluoroalkanes, H(CF2CF2)n*CH2X, where X is Cl or Br and n is 1 or 4.It is based on the cleavage of the aromatic sulfonate esters of α,α,ω-trihydroperfluoroalkan-α-ols by alkali metal halides.
- Shilin, S. V.,Florensova, O. N.,Chernov, N. F.,Voronkov, M. G.
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p. 1697 - 1699
(2007/10/02)
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- SYNTHESIS OF THREE PARTIALLY FLUORINATED ALKANESULFONIC ACIDS AS POTENTIAL FUEL-CELL ELECTROLYTES.
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The simple and effective syntheses of CH//2FCH//2SO//3H, CF//3CH//2SO//3H, AND CHF//2CF//2CH//2SO//3H have been achieved with 18. 8%, 34. 1%, and 33. 7% overall yields. The low molecuar weight partially fluorinated alkanesulfonic acids containing alpha -methylene groups can be prepared from the p-toluenesulfonates of the corresponding alcohols, via a reaction with benzyl mercaptan, followed by an oxidative chlorination of the resulting sulfides, with subsequent hydrolysis of the sulfonyl chloride. The reaction of partially fluorinated alkyl halides with sodium sulfite (Strecker's method) proved to be inefficient (very low yields) and unreliable. The sulfonate salts formed are difficult to recover and purify.
- Bunyagidj,Piotrowska,Aldridge
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p. 344 - 346
(2007/10/02)
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