- Scalable Continuous Synthesis of Grignard Reagents from in Situ-Activated Magnesium Metal
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The continuous synthesis of Grignard reagents has been investigated under continuous processing conditions using Mg turnings at variable liquid throughputs and concentrations. A novel process window easily accessible through continuous processing was employed, namely, using a large molar access of Mg turnings within the reactor and achieving Mg activation by mechanical means. A laboratory and a 10-fold-increased pilot-scale reactor setup were built and evaluated, including integrated inline analytics via ATR-IR measurements. The main goal of this work was to explore the full potential of classic Grignard reagent formation through the use of scalable flow chemistry and to allow for fast and safe process optimization. It was found that on both the laboratory and pilot scales, full conversion of the employed halides could be achieved with a single passage through the reactor. Furthermore, Grignard reagent yields of 89-100% were reached on the laboratory scale.
- Deitmann, Eva,G?ssl, Lars,Hofmann, Christian,L?b, Patrick,Menges-Flanagan, Gabriele
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- Preparation of Grignard reagents from magnesium metal under continuous flow conditions and on-line monitoring by NMR spectroscopy
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A convenient method for the classical preparation of Grignard reagents from aryl halides and magnesium using a fluidized bed reactor under continuous flow conditions was developed. The process was combined with quenching of the Grignard reagent by CO2 as a model reaction performed using a second flow reactor. The formation and quenching of the reagent was monitored by on-line 1H NMR spectroscopy. The combination of continuous flow operation for Grignard reagents with reaction monitoring by on-line NMR spectroscopy allows one to quickly optimize the working conditions.
- Goldbach, Michel,Danieli, Ernesto,Perlo, Juan,Kaptein, Bernard,Litvinov, Victor M.,Blümich, Bernhard,Casanova, Federico,Duchateau, Alexander L.L.
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- Formation of phenylmagnesium halides in toluene
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Formation reactions of phenylmagnesium chloride and bromide in toluene in the presence of one or two equivalents of diethyl ether or THF were investigated kinetically. Also, the reaction in diethyl ether and in chlorobenzene was addressed. Kinetic features of the reactions are similar to those found previously for the formation of alkylmagnesium halides in toluene and consist of rapid formation of a disolvated Grignard reagent followed by a slower formation of a monosolvated reagent. The latter is able of catalyzing the conversion of different halides into Grignard reagents. However, the contribution of Wurtz-type side reactions is considerable except when THF is used in toluene. Involving the kinetic data and the activation parameters some details of the reaction mechanism were discussed.
- Simuste, Hannes,Panov, Dmitri,Tuulmets, Ants,Nguyen, Binh T.
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- Palladium-Catalyzed Cross-Coupling of Arenediazonium Salts with Organoindium or Organobismuth Reagents
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Arylindium and isolated triarylbismuth compounds generated in situ react as nucleophiles with arenediazonium salts in palladium-catalyzed cross-coupling reactions to give substituted biphenyls.
- Riemer, Nastja,Coswig, Christin,Shipman, Mike,Schmidt, Bernd
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- Nickel-Catalyzed Alkyl-Alkyl Cross-Electrophile Coupling Reaction of 1,3-Dimesylates for the Synthesis of Alkylcyclopropanes
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Cross-electrophile coupling reactions of two Csp3-X bonds remain challenging. Herein we report an intramolecular nickel-catalyzed cross-electrophile coupling reaction of 1,3-diol derivatives. Notably, this transformation is utilized to synthesize a range of mono- and 1,2-disubstituted alkylcyclopropanes, including those derived from terpenes, steroids, and aldol products. Additionally, enantioenriched cyclopropanes are synthesized from the products of proline-catalyzed and Evans aldol reactions. A procedure for direct transformation of 1,3-diols to cyclopropanes is also described. Calculations and experimental data are consistent with a nickel-catalyzed mechanism that begins with stereoablative oxidative addition at the secondary center.
- Chen, Pan-Pan,Hong, Xin,Jarvo, Elizabeth R.,McGinnis, Tristan M.,Sanford, Amberly B.,Thane, Taylor A.
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- Design, synthesis and antifungal activity of novel selenochroman-4-one derivatives
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A series of novel selenochroman-4-one derivatives bearing semicarbazone or nitrogen heterocycle was designed, synthesized, tested antifungal activity and characterized via 1H-NMR, 13C-NMR, and HRMS. The design of the compounds is based on the principle of molecule hybrid and bioisosterism. We aimed at attaching semicarbazones or nitrogen heterocycle to the selenochroman-4-one for enhancing antifungal activity. The antifungal activity of target compounds was evaluated using the microdilution broth method in vitro test. Bioassay results indicated that some of the derivatives displayed good fungistatic activity on Candida zeylanoides, Candida albicans, Cryptococcus neoformans, resistant to fluconazole strain 103 (Candida albicans), resistant to fluconazole strain 100 (Candida albicans) and strain SC5314 (Candida albicans). All the compounds exhibit antifungal activities against the tested funguses in different levels, among them, 7 compounds of antifungal activity against several funguses is better than that of the control drug fluconazole. Based on the results, preliminary structure activity relationships (SARs) were summarized to serve as a foundation for further investigation.
- Xu, Hang,Hu, Yu-Kun,Guo, Meng-Bi,Huang, Ai-Su,Su, Xin,Guo, Chun
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- Formation of Transient Anionic Metal Clusters in Palladium/Diene-Catalyzed Cross-Coupling Reactions
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Despite their considerable practical value, palladium/1,3-diene-catalyzed cross-coupling reactions between Grignard reagents RMgCl and alkyl halides AlkylX remain mechanistically poorly understood. Herein, we probe the intermediates formed in these reactions by a combination of electrospray-ionization mass spectrometry, UV/Vis spectroscopy, and NMR spectroscopy. According to our results and in line with previous hypotheses, the first step of the catalytic cycle brings about transmetalation to afford organopalladate anions. These organopalladate anions apparently undergo SN2-type reactions with the AlkylX coupling partner. The resulting neutral complexes then release the cross-coupling products by reductive elimination. In gas-phase fragmentation experiments, the occurrence of reductive eliminations was observed for anionic analogues of the neutral complexes. Although the actual catalytic cycle is supposed to involve chiefly mononuclear palladium species, anionic palladium nanoclusters [PdnR(DE)n]?, (n=2, 4, 6; DE=diene) were also observed. At short reaction times, the dinuclear complexes usually predominated, whereas at longer times the tetra- and hexanuclear clusters became relatively more abundant. In parallel, the formation of palladium black pointed to continued aggregation processes. Thus, the present study directly shows dynamic behavior of the palladium/diene catalyst system and degradation of the active catalyst with increasing reaction time.
- Kolter, Marlene,Koszinowski, Konrad
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- Ni-Catalyzed C(sp2)-H alkylation ofN-quinolylbenzamides using alkylsilyl peroxides as structurally diverse alkyl sources
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A Ni-catalyzed direct C-H alkylation ofN-quinolylbenzamides using alkylsilyl peroxides as alkyl-radical precursors is described. The reaction forms a new C(sp3)-C(sp2) bondviathe selective cleavage of both C(sp3)-C(sp3) and C(sp2)-H bonds. This transformation shows a high functional-group tolerance and, due to the structural diversity of alkylsilyl peroxides, a wide range of alkyl chains including functional groups and complex structures can be introduced at theortho-position of readily availableN-quinolylbenzamide derivatives. Mechanistic studies suggest that the reaction involves a radical mechanism.
- Kano, Taichi,Maruoka, Keiji,Matsumoto, Akira,Sakurai, Shunya,Tsuzuki, Saori
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supporting information
p. 7942 - 7945
(2021/08/17)
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- Room-Temperature Palladium(II)-Catalyzed Direct 2-Arylation of Indoles with Tetraarylstannanes
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A palladium(II)-catalyzed direct 2-arylation of indoles by tetraarylstannanes with oxygen (balloon) as the oxidant at room temperature has been developed. Various tetraarylstannanes can be employed as aryl sources for 2-arylation of indoles in up to 89% yield, providing a practical and efficient catalytic protocol for accessing 2-arylindoles.
- Liu, Yuxia,Wang, Chao,Huang, Linjuan,Xue, Dong
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supporting information
p. 1613 - 1618
(2020/09/15)
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- Structure-Activity Relationship Studies of α-Ketoamides as Inhibitors of the Phospholipase A and Acyltransferase Enzyme Family
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The phospholipase A and acyltransferase (PLAAT) family of cysteine hydrolases consists of five members, which are involved in the Ca2+-independent production of N-acylphosphatidylethanolamines (NAPEs). NAPEs are lipid precursors for bioactive N-acylethanolamines (NAEs) that are involved in various physiological processes such as food intake, pain, inflammation, stress, and anxiety. Recently, we identified α-ketoamides as the first pan-active PLAAT inhibitor scaffold that reduced arachidonic acid levels in PLAAT3-overexpressing U2OS cells and in HepG2 cells. Here, we report the structure-activity relationships of the α-ketoamide series using activity-based protein profiling. This led to the identification of LEI-301, a nanomolar potent inhibitor for the PLAAT family members. LEI-301 reduced the NAE levels, including anandamide, in cells overexpressing PLAAT2 or PLAAT5. Collectively, LEI-301 may help to dissect the physiological role of the PLAATs.
- Zhou, Juan,Mock, Elliot D.,Al Ayed, Karol,Di, Xinyu,Kantae, Vasudev,Burggraaff, Lindsey,Stevens, Anna F.,Martella, Andrea,Mohr, Florian,Jiang, Ming,Van Der Wel, Tom,Wendel, Tiemen J.,Ofman, Tim P.,Tran, Yvonne,De Koster, Nicky,Van Westen, Gerard J.P.,Hankemeier, Thomas,Van Der Stelt, Mario
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p. 9340 - 9359
(2020/10/19)
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- Method for synthesizing anthracene OLED intermediate
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The invention relates to a method for synthesizing anthracene OLED (organic light emission diode) intermediates. According to the method, the anthracene OLED intermediates are prepared from an aryl Grignard reagent and aryl halide through a Kumada cross-coupling reaction at the temperature of 25-35 DEG C under the protection of inert atmosphere and in the presence of a catalyst. The method has thebeneficial effects as follows: the NiCl2(dppp) catalyst is cheap and easily available, and a prepared product is high in yield and high in purity; the reaction condition is the room temperature, energy is saved, and the reaction condition is milder.
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Paragraph 0023-0024; 0030-0032
(2020/11/23)
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- Synthesis of trifluoromethyl moieties by late-stage copper (I) mediated nucleophilic fluorination
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The nucleophilic fluorination of bromodifluoromethyl derivatives mediated by the complex (PPh3)3CuF is described. Under the reaction conditions, different trifluoroacetates, trifluoroketones, trifluoroarenes and trifluoroacetamides were obtained in good yields.
- Bermejo Góme, Antonio,González, Miguel A. Cortés,Lübcke, Marvin,Johansson, Magnus J.,Schou, Magnus,Szabó, Kálmán J.
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- Nickel-Catalyzed Asymmetric Kumada Cross-Coupling of Symmetric Cyclic Sulfates
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Nickel-catalyzed enantioselective cross-couplings between symmetric cyclic sulfates and aromatic Grignard reagents are described. These reactions are effective with a broad range of substituted cyclic sulfates and deliver products with asymmetric tertiary carbon centers. Mechanistic experiments point to a stereoinvertive SN2-like oxidative addition of a nickel complex to the electrophilic substrate.
- Eno, Meredith S.,Lu, Alexander,Morken, James P.
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supporting information
p. 7824 - 7827
(2016/07/11)
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- Facile Hydrogenolysis of C(sp3)–C(sp3) σ Bonds
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The modification of benzylic quaternary, tertiary, and secondary carbon centers through palladium-catalyzed hydrogenolysis of C(sp3)–C(sp3) σ bonds is presented. When benzyl Meldrum's acid derivatives bearing quaternary benzylic centers are treated under mild hydrogenolysis conditions – palladium on carbon and atmospheric pressure of hydrogen – aromatics substituted with tertiary benzylic centers and Meldrum's acid are obtained with good to excellent yield. Analogously, substrates containing tertiary or secondary benzylic centers yield aromatics substituted with secondary benzylic centers or toluene derivatives, respectively. Furthermore, this strategy is used for the high yielding synthesis of diarylmethanes. The scope of the reductive dealkylation reaction is explored and the limitations with respect to steric and electronic factors are determined. A mechanistic analysis of the reaction is described that consisted of deuterium labelling experiments and hydrogenolysis of enantioenriched derivatives. The investigation shows that the C(sp3)–C(sp3) σ bond-cleaving events occur through a hybrid SN1/SN2 mechanism, in which the palladium center displaces a carbon-based leaving group, namely Meldrum's acid, with inversion of configuration, followed by reductive elimination of palladium to furnish a C?H bond. (Figure presented.).
- Fillion, Eric,Beaton, Eric,Nguyen, Yen,Wilsily, Ashraf,Bondarenko, Ganna,Jacq, Jér?me
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supporting information
p. 3422 - 3434
(2016/11/13)
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- Enantioselective synthesis of diaryl aziridines using tetrahydrothiophene- based chiral sulfides as organocatalysts
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This work describes catalytic and asymmetric aziridinations (15 examples, 95-98% ee) of benzyl bromide and imines via the imino Corey-Chaykovsky reaction using (thiolan-2-yl)diarylmethanol benzyl ether as an organocatalyst. The catalyst and analogues thereof were prepared through an expeditious and efficient synthetic route featuring a double nucleophilic substitution and Shi epoxidation as key steps.
- Huang, Meng-Ting,Wu, Hsin-Yi,Chein, Rong-Jie
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supporting information
p. 1101 - 1103
(2014/01/17)
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- Synthesis of oxazolidin-2-ones and imidazolidin-2-ones directly from 1,3-diols or 3-amino alcohols using iodobenzene dichloride and sodium azide
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A general and efficient method for the synthesis of oxazolidin-2-ones and imidazolidin-2-ones directly from 1,3-diols and 3-amino alcohols has been developed using the same reagent combination of iodobenzene dichloride (PhICl2) and sodium azide (NaN3).
- He, Tian,Gao, Wen-Chao,Wang, Wei-Kun,Zhang, Chi
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supporting information
p. 1113 - 1118
(2014/04/03)
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- Cyclopalladation of telluro ether ligands: Synthesis, reactivity and structural characterization
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Treatment of [PdCl2(PhCN)2] with diaryl telluride in 1:2 molar ratio gave mononuclear palladium complexes, trans-[PdCl2(TeR2)2] (1) (R = Mes (1a) (Mes = 2,4,6-trimethylphenyl), Ph (1b), o-tol (1c) (o-tol = ortho-tolyl)). Reaction of [PdCl2(TeMes2)2] with one equivalent of [PdCl2(PhCN)2] or Na2PdCl4 with TeRR′ afforded chloro-bridged binuclear complexes, [Pd2(μ-Cl)2Cl2(TeRR′)2] (2) (R/R′ = Mes/Mes (2a); Mes/Ph (2b); Ph/Ph (2c)). A toluene-methanol solution of trans-[PdCl2(TeMes2)2] on refluxing for 30 minutes yielded a binuclear cyclopalladated complex, [Pd2(μ-Cl)2{CH2C6H2(4,6-Me2)TeMes)}2] (3). When the refluxing was prolonged, a mononuclear complex cis-[PdCl2{MesTeCH2C6H2(4,6-Me2)TeMes}] (4) was isolated. Treatment of palladium acetate with TeMes2 afforded an acetato-bridged analogue of 3, [Pd2(μ-OAc)2{CH2C6H2(4,6-Me2)TeMes}2] (5a) together with a very minor component, a tetranuclear complex, [Pd(μ-OAc)(μ-TeMes)]4 (6). This reaction with unsymmetrical tellurides, MesTeR, also gave cyclopalladated complexes [Pd2(μ-OAc)2{CH2C6H2(4,6-Me2)TeR}2] (R = o-tol (5b) and Ph (5c)) in which 2-methyl of the mesityl group of the telluride was exclusively metallated. The complex trans-[PdCl2(TeMes2)2] on refluxing in xylene gave palladium telluride, Pd7Te3. These complexes were characterized by elemental analyses, IR and NMR (1H, 13C and 125Te) spectroscopy. The molecular structures of trans-[PdCl2(TeMes2)2] (1a), [Pd2(μ-Cl)2Cl2(TeMes2)2]·2acetone (2a·2acetone), cis-[PdCl2{MesTeCH2C6H2(4,6-Me2)TeMes}] (4), [Pd2(μ-OAc)2{CH2C6H2(4,6-Me2)TeMes)}2]·toluene (5a·toluene), [Pd2(μ-OAc)2{CH2C6H2(4,6-Me2)Tetol-o}2] (5b) and [Pd(μ-OAc)(μ-TeMes)]4 (6) were established by single crystal X-ray diffraction analyses. The mononuclear complex 1a was isolated in two polymorphic forms each with the trans configuration. This journal is
- Kolay, Siddhartha,Kumar, Mukesh,Wadawale, Amey,Das, Dasarathi,Jain, Vimal K.
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supporting information
p. 16056 - 16065
(2015/01/09)
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- A chiron approach for the total synthesis of crassalactone A
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The total synthesis of crassalactone A (1) has been achieved in twelve steps starting from commercially available 1,5-D-gluconolactone. Still-Gennari olefination, one-pot deprotection, and lactonization are the key reactions involved in the synthesis. Copyright
- Yadav, Jhillu Singh,Rao, Gokada Maheswara,Thirupathaiah, Bodakuntala
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p. 2233 - 2239
(2014/01/06)
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- Selective introducing of aryl and amino groups: Reaction of benzanthrone and organometallic reagents
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The reaction of benzanthrone and aryl magnesium bromides produced 6-aryl-substituted benzanthrones in moderate to good yields. Similarly, 6-alkylaminobenzanthrones were selectively prepared by the reaction of benzanthrone and lithium alkylamides. In contrast, for the lithium arylamides, the arylamino groups were selectively introduced at the 4-position of the benzanthrone.
- Umeda, Rui,Namba, Teruaki,Yoshimura, Tomohiro,Nakatsukasa, Masamichi,Nishiyama, Yutaka
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p. 1526 - 1531
(2013/02/23)
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- Photo-induced electron transfer in a pyrenylcarbazole containing polymer-multiwalled carbon nanotube composite
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A polymer incorporated with a pyrenylcarbazole pendant poly(12-(3-(pyren-1- yl)-carbazol-9-yl)dodecyl methacrylate, denoted as PCP) was synthesized and applied in the functionalization of multi-walled carbon nanotubes (MWCNTs) by noncovalent π-π interaction. The PCP-MWCNT hybrids were isolated and characterized by SEM, TEM, and UV-visible absorption and emission spectroscopies. The strong interaction between PCP and the MWCNT in a 1,1,2,2-tetrachloroethane (TCE) solution was studied. It demonstrated an effective quenching effect on emission from PCP by the MWCNTs. DFT calculations showed electron delocalization between the pyrene and carbazole moieties. The LUMO of PCP is mainly located on the pyrene moiety while the LUMO + 1 is predominantly positioned on the carbazole moiety. Femtosecond transient absorption (TA) experiments determined the characteristic TA peaks of the excited states, which have contributions from both the pyrene and carbazole moieties. The excited state lifetime of the polymer PCP was measured to be 659 ps and the photo-excited electrons were injected into the MWCNTs very effectively on a time scale of 420 fs.
- Yu, Lihong,Lo, Kin Cheung,Xi, Jingyu,Phillips, David Lee,Chan, Wai Kin
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supporting information
p. 1833 - 1842
(2013/06/27)
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- Reversible near-infrared fluorescent probe introducing tellurium to mimetic glutathione peroxidase for monitoring the redox cycles between peroxynitrite and glutathione in vivo
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The redox homeostasis between peroxynitrite and glutathione is closely associated with the physiological and pathological processes, e.g. vascular tissue prolonged relaxation and smooth muscle preparations, attenuation hepatic necrosis, and activation matrix metalloproteinase-2. We report a near-infrared fluorescent probe based on heptamethine cyanine, which integrates with telluroenzyme mimics for monitoring the changes of ONOO-/GSH levels in cells and in vivo. The probe can reversibly respond to ONOO- and GSH and exhibits high selectivity, sensitivity, and mitochondrial target. It is successfully applied to visualize the changes of redox cycles during the outbreak of ONOO- and the antioxidant GSH repair in cells and animal. The probe would provide a significant advance on the redox events involved in the cellular redox regulation.
- Yu, Fabiao,Li, Peng,Wang, Bingshuai,Han, Keli
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supporting information
p. 7674 - 7680
(2013/07/05)
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- BICYCLO-HEPTAN-2-AMINES
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The present invention provides bicyclo-heptan-2-amines that selectively bind to the sigma-2 receptor and are useful in the treatment of diseases related to the sigma-2 receptor, for example, cancer and neurological disorders.
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(2012/07/31)
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- Manganese(III)-assisted specific intramolecular addition
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Oligomethylene-tethered -alkenyl 3-oxobutanoates and 3-oxobutanamides underwent manganese(III)-mediated oxidative intramolecular addition to produce dihydrofuran-fused macrolides and macrocyclic amides from 8 to 26 members. A similar reaction of the oligooxamethylene-tethered -alkenyl 3-oxobutanoates also gave dihydrofuran-fused crown ether type macrolides which had a phase-transfer ability with sodium and potassium picrates. The manganese(III)-assisted specific intramolecular addition could be explained by the -complexation of the -alkenyl part with the manganese(III) enolate. Georg Thieme Verlag Stuttgart - New York.
- Ito, Yosuke,Jogo, Shunsuke,Fukuda, Noriko,Okumura, Ryo,Nishino, Hiroshi
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experimental part
p. 1365 - 1374
(2011/06/17)
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- PROCESS FOR THE PREPARATION OF GRIGNARD COMPOUNDS
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The invention relates to a process for the preparation of Grignard compounds using a continuous method which involves the reaction of an organic halide dissolved in an organic solvent with metallic magnesium which, together with the activator solution in an organic solvent, fills the flow reactor or optionally a system of flow reactors, and subsequently, the resulting reaction mixture is fed into the terminal flow reactor containing metallic magnesium in order to achieve complete conversion of the organic halide, whereby preferably the organic solvent is re-circulated to flow reactors in a form of vapour.
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Page/Page column 9
(2010/11/03)
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- Gold-catalyzed intramolecular [3+2] cycloadditions of 1-Aryl-1-allene-6- enes
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Treatment of 1-aryl-1-allen-6-enes with [PPh3AuCl]/AgSbF 6 (5 mol%) in CH2Cl2 at 25°C led to intramolecular [3+2] cycloadditions, giving cis-fused dihydrobenzo[a]fluorene products efficiently and selectively. The reactions proceeded with initial formation of trans/cis mixtures of 2-alkyl-1-isopropy1-2-phenyl-1,2- dihydronaphthalene cations B, which were convertible into the desired cis-fused cycloadducts through the combined action of a gold catalyst and a Bronsted acid. Theoretic calculation supports the participation of the trans-B cation as reaction intermediate. Although HOTf showed similar activity towards several 1-aryl-1-allen-6-enes, it lacks generality for this cycloaddition reaction.
- Chaudhuri, Rupsha,Liao, Hsin-Yi,Liu, Rai-Shung
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experimental part
p. 8895 - 8901
(2010/04/05)
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- Selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. Discovery of a morpholinopropylaminobenzimidazole derivative (TMC353121)
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A preceding paper (Bonfanti et al. J. Med Chem. 2007, 50, 4572-4584) reported the optimization of the pharmacokinetic profile of substituted benzimidazoles by reducing their tissue retention. However, the modifications that were necessary to achieve this goal also led to a significant drop in anti-RSV activity. This paper describes a molecular modeling study followed by a lead optimization program that led to the recovery of the initial potent antiviral activity and the selection of TMC353121 as a clinical candidate.
- Bonfanti, Jean-Fran?ois,Meyer, Christophe,Doublet, Frédéric,Fortin, Jér?me,Müller, Philippe,Queguiner, Laurence,Gevers, Tom,Janssens, Peggy,Szel, Heidi,Willebrords, Rudy,Timmerman, Philip,Wuyts, Koen,Van Remoortere, Pieter,Janssens, Frans,Wigerinck, Piet,Andries, Koen
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p. 875 - 896
(2008/09/19)
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- RENIN INHIBITORS
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Described are compounds that bind to aspartic proteases to inhibit their activity. They are useful in the treatment or amelioration of diseases associated with aspartic protease activity. Also described are methods of use of the compounds described herein in ameliorating or treating aspartic protease related disorders in a subject in need thereof.
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Page/Page column 140-141
(2009/01/23)
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- Thiazepine inhibitors of HIV-1 integrase
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The present invention discloses non-catechol compounds, such as thiazolothiazepines, and analogs and derivatives thereof, which are anti-integrase inhibitors. The compounds, which are useful as treatments for HIV disease, include compounds (I), (II), (III), or pharmaceutically acceptable salts thereof wherein A is thiazole, benzene, naphthalene, pyridine, pyrimidine, pyrazine, or quinoline; R is one or more of H, halogen, lower alkyl, lower alkoxy, NO2, lower ester or carboxylic acid; X—Y is CH2—S, S—CH2, CH2—O, CH2—S(O). S(O)—CH2, CH2—CH2, CH2—CH2—CH2, or CH2—CH2—CH2—CH2; R4 is H or hydroxy; R5 is H, phenyl, or alkylamine; W is S or O; and R6 is H, substituted or unsubstituted alkyl or amine; and Z is S, O, CH2, CH2CH2, or C═O.
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Page/Page column 16-17
(2008/06/13)
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- N-(3-(IMIDAZO [1,5-A]PYRIMIDIN-4-YL)PHENYL]-SULFONAMIDES AND N-[3-(IMIDAZO[1,5-A]PYRIMIDIN-4-YL)-PHENYL]-CARBOXAMIDES AND THEIR USE AS GABAA RECEPTOR MODULATORS
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The present invention relates to compounds of formula I wherein R1, R2, R3 and X are as defined in the claims. The compounds have specific affinity for the GABAA receptor and are therefore useful in the treatment and prevention of diseases modulated by the 1 and 2-GABAA receptors.
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Page/Page column 18-19
(2008/06/13)
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- Radical clocks and electron transfer. Comparison of crown ether effects on the reactivity of potassium and magnesium towards 1-bromo-2-(3-butenyl)benzene. the incidence of homogeneous versus heterogeneous electron transfer on selectivity
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The reaction of the title precursor of the aryl radical clock 1-bromo-2-(3-butenyl)benzene, 1Br, towards potassium and magnesium in THF was studied in the presence and absence of various additives, at ambient and low temperatures. The additives were cis-dicyclohexano-18-crown-6 or tert-butyl alcohol; the first one to render soluble potassium by forming its alkalide, the second to distinguish carbanionic from radical cyclization. The addition of 1Br to a THF stirred suspension of potassium pieces yields remarkably low amounts of products resulting from radical cyclization, in contrast to the amounts reported by Bunnett and Beckwith's group for the reaction in 67% ammonia-33% tert-butyl alcohol medium. The amount of cyclized products obtained with potassium pieces in THF is in the same range as that observed in the reaction of magnesium with 1Br in THF. This similarity allows us to discard the earlier triad hypothesis that we proposed to account for the unexpectedly low amounts of cyclized products of aryl halides radical clocks in Grignard reagent formation. The addition of crown ethers to the THF reaction medium induces contrasting effects for potassium and magnesium. A distinctive increase in the radical cyclization is observed for potassium, whereas the addition of crown inhibits the formation of Grignard reagent more efficiently when the solvent is diethyl ether than when it is THF. The observed effects are explained by putting in perspective the metal reactive dissolution with elementary steps occurring in the vicinity of a cathode. The reaction of potassium pieces or magnesium turnings is comparable to the heterogeneous electron transfer occurring at a cathode whereas the reaction of potassium in the presence of crown ether is comparable to homogeneous conditions of electron transfer obtained in redox catalysis. A discussion of the dianion hypothesis for the Grignard reaction of aryl halides is provided and the importance of considering the reactivity of reactive metal dissolution (or organic corrosion) in the framework of recent progress made in the modelling of electrode reactivity is emphasized. This paper shows that caution should be taken when radical clocks are used to study reactions at the metal-solution interface. More specifically, the non-bservation of rearranged products from the radical clock (even for the very rapid ones) under these conditions does not necessary imply that there is no radical intermediate along the dominant reaction channel. This pattern of reactivity strongly contrasts with that usually observed when radical clocks are used in homogeneous media. The leading parameters in the rearranged/unrearranged products ratio seem to be the time that the reactive species (radical anions) created by the first electron transfer spend in the close vicinity of this surface, the rate constant of rearrangement of the radical formed by the cleavage of the radical anion and the redox properties of this radical. Copyright
- Hazimeh, Hassan,Mattalia, Jean-Marc,Marchi-Delapierre, Caroline,Barone, Rene,Nudelman, Norma S.,Chanon, Michel
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p. 1145 - 1160
(2007/10/03)
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- BENZIMIDAZOLE DERIVATIVES
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A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof; wherein R1-R7 are as disclosed in the specification and pharmaceutical uses thereof.
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Page/Page column 51
(2008/06/13)
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- 1-PYRIDIN-4-YL-UREA DERIVATIVES
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The invention relates to novel 1-pyridyn-4-yl urea derivatives and related compounds and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as neurohormonal antagonists.
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- Quinuclidine compounds and drugs containing the same as the active ingredient
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The present invention provides an excellent squalene synthesizing enzyme inhibitor. Specifically, it provides a compound (I) represented by the following formula, a salt thereof or a hydrate of them. In which R1 represents (1) hydrogen atom or (2) hydroxyl group; HAr represents an aromatic heterocycle which may be substituted with 1 to 3 groups; Ar represents an optionally substituted aromatic ring; W represents a chain represented by (1) —CH2—CH2— which may be substituted, (2) —CH=CH— which may be substituted, (3) —C≡C—, (4) —NH—CO—, (5) —CO—NH—, (6) —NH—CH2—, (7) —CH2—NH—, (8) —CH2—CO—, (9) —CO—CH2—, (10) —NH—S(O)l—, (11) —S(O)l—NH—, (12) —CH2—S(O)— or (13) —S(O)l—CH2— (l denotes 0, 1 or 2); and X represents a chain represented by (1) a single bond, (2) an optionally substituted C1-6 alkylene chain, (3) an optionally substituted C2-6 alkenylene chain, (4) an optionally substituted C2-6 alkynylene chain, (5) a formula —Q— (wherein Q represents oxygen atom, sulfur atom, CO or N(R2) (wherein R2 represents a C1-6 alkyl group or a C1-6 alkoxy group)), (6) —NH—CO—, (7) —CO—NH—, (8) —NH—CH2—, (9) —CH2—NH—, (10) —CH2—CO—, (11) —CO—CH2—, (12) —NH—S(O)m—, (13) —S(O)m—NH—, (14) —CH2—S(O)m—, (15) —S(O)m—CH2— (wherein m denotes 0, 1 or 2) or (16) —(CH2)n—O— (wherein n denotes an integer from 1 to 6).
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- Method for producing alkyl-bridged ligand systems and transition metal compounds
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The invention relates to a method for producing highly substituted alkyl-bridged ligand systems on the basis of indene derivatives and transition metal compounds. Said alkyl-bridged ligand systems can be obtained in high yields using this method.
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- 2,2-(Diaryl)vinylphosphine compound, palladium catalyst thereof, and process for producing arylamine, diaryl, or arylalkyne with the catalyst
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A novel 2,2-(diaryl)vinylphosphine compound represented by the following general formula (1): (wherein R1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, etc.; R2, R3, R4, R5, R6, and R7 may be the same or different and each is an alkyl group having 1 to 6 carbon atoms, an alicyclic group having 5 to 7 carbon atoms, etc., provided that R4 and R5 taken together and/or R6 and R7 taken together may represent a fused benzene ring, a substituted fused benzene ring, a trimethylene group, etc.; and p, q, r, and s each is 0 to 5, provided that p+q and r+s each is in the range of from 0 to 5); a palladium-phosphine catalyst obtained by causing a palladium compound to act on the novel 2,2-(diaryl)vinylphosphine compound; and a process for obtaining an arylamine, a diaryl and an arylalkyne in the presence of the palladium-phosphine catalyst.
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- Novel arylamine compound and organic electroluminescence device
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A novel arylamine compound represented by the following general formula (1): wherein R1 and R2 each independently represent an alkyl group, an alkoxyl group, an aryl group, an arylalkyl group or an aryloxyl group, Ar1 to Ar4 each independently represent an aryl group or a heterocyclic group, with provisos that at least two of Ar1 to Ar4 each represent m-biphenyl group or a biphenyl group substituted with aryl groups and the others of Ar1 to Ar4 each represent biphenyl group and that, when the biphenyl group substituted with aryl groups is a biphenyl group substituted with two aryl groups, the others of Ar1 to Ar4 each represent an aryl group; and an organic electroluminescence device comprising a layer of organic compounds which comprises the novel arylamine compound. The organic electroluminescence device has a high luminance, excellent heat resistance and a long life and emits light; at a high efficiency. The novel arylamine compound provides the advantageous properties to the organic electroluminescence device.
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- Chiral hydride complexes
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Novel chiral boron and aluminum hydride complexes, compositions comprising the chiral hydride complexes, and methods for their synthesis and use are described. The novel chiral hydride complexes are of the formulas: PA1 MBH4-n-a (R*)n (R')a ; PA1 MBH2-b (R**) (R')b ; PA1 MBH(R***); PA1 MBH(R*) (R"); PA1 MAlH4-n-a (R*)n (R')a ; PA1 MAlH2-b (R**)(R')b ; PA1 MAlH(R***); and PA1 MAlH(R*) (R"), PAL wherein PA1 M is Na+, Li+ or K+ ; PA1 each R* is independently a monodentate chiral ligand; PA1 R** is a bidentate chiral ligand; PA1 R*** is a tridentate chiral ligand; PA1 R' is a monodentate achiral ligand; PA1 R" is a bidentate achiral ligand; PA1 n is 1-3; PA1 a is 0-2; and PA1 b is 0-1, PAL with the proviso that n+a3, and with the further proviso that when R** is S-BINOL, M is not Li+.
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- Kinetics and Thermodynamics of Oxidation of Magnesium with Phenyl Halides in Benzene in the Presence of Diethyl Ether
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The equilibrium constants and the enthalpies and entropies of adsorption of phenyl chloride and phenyl iodide on the surface of magnesium during oxidation in benzene were determined. The reaction scheme explaining acceleration of conversion and increase in the fraction of products of the Wuertz reaction with increasing concentration of oxidant was suggested.
- Maslennikov,Spirina
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p. 274 - 276
(2007/10/03)
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- Nature of Organic Radical in Hydrocarbon Halide and Character of Its Adsorption on Magnesium Surface during Oxidation of the Metal
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Adsorption of various hydrocarbon bromides on magnesium surface from a mixture of diethyl ether and benzene during magnesium oxidation was studied. The character of adsorption, the reaction rate, and the yields of the Grignard reagents are determined by the structure of the organic radical in the oxidant molecule.
- Maslennikov,Spirina
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p. 1876 - 1877
(2007/10/03)
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- Triazole derivatives
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The present invention relates to a novel glycerol derivative and a process for preparing the same, and a process for preparing a triazole derivative. According to the present invention, an optical active 2-arylglycerol derivative which is a novel and useful as a synthetic intermediate of medicament can be provided and furthermore, (R)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazole-1-yl)-propane-1,2-diol which is useful as an antifungal agent can be prepared.
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- Method for preparation of optically active diarylalanines
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A method for preparing a diarylalanine compound is provided. The method includes reacting a diarylaminopropanediol with a reducing agent to form a diarylaminopropanol compound and/or contacting a serine ester derivative with an aryl metal reagent to form diarylaminopropanediol. A diarylmethyloxazolidinone compound is also provided.
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- C-GLYCOSIDE ANALOGUES OF N-(4-HYDROXYPHENYL)RETINAMIDE-O-GLUCURONIDE
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The present invention provides breast cancer chemopreventive arylamide analogues of retinoic acid, more particularly C-glycoside analogues of N-(4-hydroxyphenyl)retinamide-O-glucuronide and N-glycoside analogue of retinoyl beta-glucuronide that resist both beta-glucuronidase mediated enzymatic hydrolysis as well as acid catalyzed hydrolysis. Specifically, the drugs include 4-(retinamido)phenyl-C-glucuronide; 4-(retinamido)phenyl-C-glucoside; 4-(retinamido)benzyl-C-xyloside; 4-(retinamido)benzyl-C-glucoside; 4-(retinamido)benzyl-C-glucuronide; 4-(retinamido)phenyl-C-xyloside, 1-(B-D-lucopyranosyl) retinamide and 1-(D-glucopyranosyluronosly) retinamide. The invention also relates to a method for making such drugs.
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- Hydro-ethano-indeno-pyridines
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A compound of formula I STR1 wherein X, V, W, Y, Z, R, a, b, c, and d are as described herein. These compounds are useful in the treatment of tumors, allergies, bronchoconstriction and CNS diseases and conditions.
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- PHOSPHORUS-CONTAINING HMG-COA REDUCTASE INHIBITORS, NEW INTERMEDIATES AND METHOD
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Compounds which are useful as inhibitors of cholesterol biosynthesis and thus as hypocholesteroleumic agents are provided which have the structure STR1 wherein R is OH, or salts thereof or lower alkoxy; R. sup.x is H or alkyl;X is--CH 2--,--
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- Preparation of polyfluoroenolates
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Polyfluoroenolates, R1 CX=CR2 OM (R1 is F or a perfluoroalkyl group, R2 is a perfluoroalkyl group, X is F, Cl or Br), are easily formed at good yields by dehydrohalogenation reaction of polyfluoroalcoholates, R1 CXY--CR2 HOM (Y is F, Cl or Br), with a strong base such as, e.g., an alkyl metal or an aryl metal. A typical example of the polyfluoroenolates is lithium pentafluoro-2-propenolate which is obtained from hexafluoro-2-propanolate. A polyfluoroenolate of the above general formula can be converted into another polyfluoroenolate having an alkyl or aryl group in place of the halogen X by reaction with an alkyl or aryl metal.
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- Synthesis and Liquid Crystal Behaviour of Further 4,4"-Disubstituted 2'-Fluoro-1,1':4',1"-Terphenyls
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Further to earlier work on the liquid crystal properties of fluoro-1,1':4',1"-terphenyls we have now extended this series to include terminally fluoro- and cyano-substituted 2'-fluoro-1,1':4',1"-terphenyls, chiral 2'-fluoro-1,1':4',1"-terphenyls, and esters derived from 2'-fluoro-1,1':4',1"-terphenyls and incorporating the alkylcyclobutyl group.The preparations and transition temperatures for these series of compounds are presented and their transition temperatures and mesophase types are discussed.An interesting result from this work was the appearence of an S*C phase for one chiral homologue and of SC phases for the esters incorporating the alkylcyclobutyl group.The SC formation is attributed to the presence of the fluoro-substituent.Keywords: terphenyls, fluoroterphenyls, smectic C phases, cyclobutyl esters.
- Chan, L. K. M.,Gray, G. W.,Lacey, D.,Toyne, K. J.
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p. 209 - 240
(2007/10/02)
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- Monoorganylation of dihaloaromatics
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Process for the monoalkylation/monoarylation of dihaloaromatic compounds by treating the latter with selected magnesium or zinc organometallic reagents in the presence of a nickel/bidentate or tridentate phosphorus ligand. The products are intermediates to agricultural and pharmaceutical compounds.
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- Pentacyclic derivatives of piperazine
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Compounds of formula (I): STR1 wherein: X is CH2, O, S or NR wherein R is hydrogen or C1-4 alkyl; Y and Z are independently selected from hydrogen, C1-4 alkyl, C1-4 alkoxy, halogen or CF3 ; R1 is hydrogen, C1-6 alkyl, phenyl or phenyl-C1-4 alkyl any of which phenyl moieties may be substituted by one or more of C1-6 alkyl, C1-6 alkoxy, halogen or CF3 ; R2 is hydrogen, OH, C1-6 alkoxy, phenyl-C1-4 alkoxy, C1-7 acyloxy or NR4 R5 wherein R4 and R5 are independently selected from hydrogen or C1-6 alkyl; R4 is hydrogen and R5 is OH or C1-4 alkoxy; or R4 and R5 together form C3-6 polymethylene optionally interrupted by O or NR6 where R6 is hydrogen or C1-4 alkyl; or together with R1 forms an oxo group or =NOR7 wherein R7 is hydrogen or C1-6 alkyl; and R3 is hydrogen or C1-6 alkyl have useful pharmacological activity, processes for their preparation and their use.
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- Esters of phenalkyloxycarbonylamino acids
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Novel esters of phenylalkyloxy- or phenylalkylthioacylamino acids and pyridylalkyloxy- or pyridylalkylthioacylamino acids, synthesis thereof, intermediates therefor, and the use of said esters for the control of weeds.
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- 3-Fluorobenzodiazepines
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3-Fluoro-2,3-dihydro-1H-1,4-benzodiazepin-2-ones of the formula STR1 wherein R1 is H, alkyl or fluorinated alkyl of 1-4 carbon atoms and up to 9 fluorine atoms or cycloalkylalkyl of 4-8 carbon atoms; R2 is phenyl; monohalophenyl or pyridyl; R3 is F, Cl, Br or NO2, and physiologically acceptable acid addition salts thereof, are central nervous system depressants.
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