- A synthesis of 1-aryl-3,5-dioxo-tetrahydro-1H-pyrazols from reaction of alkyl isocyanides, isopropylidene Meldrum's acid and arylhydrazines
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The reaction between alkyl isocyanides and isopropylidene Meldrum's acid in the presence of arylhydrazines leads to functionalised 1-aryl-3,5-dioxo- tetrahydro-1H-pyrazols in good yields.
- Yavari, Issa,Sabbaghan, Maryam,Ghazanfarpour-Darjani, Majid,Hossaini, Zinatossadat
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Read Online
- Facile preparation and purification of mono tert-butyl malonate
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Reaction of Meldrum's acid with tert-BuOH gives tert-BuO 2CCH2CO2H, which can be easily purified via its corresponding crystalline ammonium salt and subsequent acidification. Copyright Taylor & Francis LLC.
- Tararov, Vitali I.,Korostylev, Andrei,Koenig, Gerd,Boerner, Armin
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Read Online
- Alkylidene Meldrum's Acids as Platforms for the Vinylogous Synthesis of Dihydropyranones
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Upon Br?nsted base organocatalysis, ketone-derived alkylidene Meldrum's acids proved to be competent vinylogous platforms able to undergo a formal (4+2) cycloaddition reaction with dihydro-2,3-furandione, providing an unprecedented route to 3,6-dihydropyran-2-ones as spiro[4.5]decane derivatives with up to 98 % ee thanks to the commercially available Takemoto catalyst. Preliminary investigation showed that this reaction could be extended to other activated ketones, establishing these alkylidene Meldrum's acids as a novel C4-synthon in the vinylogous series.
- Wittmann, Stéphane,Martzel, Thomas,Pham Truong, Cong Thanh,Toffano, Martial,Oudeyer, Sylvain,Guillot, Régis,Bournaud, Chloée,Gandon, Vincent,Brière, Jean-Fran?ois,Vo-Thanh, Giang
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supporting information
p. 11110 - 11114
(2021/04/09)
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- Synthesis of Cyclopentadienes for Cyclopentadienyl Ligands via Cp*RhIII-Catalyzed Formal sp3C-H Activation/Spiroannulations
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An efficient Cp*RhIII-catalyzed formal C(sp3)-H activation/spiroannulation of alkylidene Meldrum's acids with alkynes has been developed using catalytical Cu(OAc)2 and air as the oxidant. This reaction demonstrates a new and straightforward approach to spirocyclopentadienes with Meldrum's acid moieties in good to excellent yields under mild reaction conditions with a broad substrate scope. Notably, this protocol provides a novel and straightforward approach to cyclopentadienes with various substitution patterns and the corresponding cyclopentadienyl-type ligands from simple substrates.
- Wang, Yongzhuang,Huang, Xiaoli,Wang, Qin,Tang, Yuhai,Xu, Silong,Li, Yang
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supporting information
p. 757 - 761
(2021/02/01)
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- GPR40 receptor stimulant, and preparation method, pharmaceutical composition and application thereof
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The invention discloses a GPR40 receptor stimulant, and a preparation method, a pharmaceutical composition and application thereof. The invention particularly discloses a GPR40 receptor stimulant shown in general formula (I) and pharmacologically acceptable salt thereof, a preparation process of the compound, a pharmaceutical composition containing the compound of general formula (I), and application of the compound and the pharmaceutical composition in anti-diabetes.
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Paragraph 0163; 0199; 0218-0220
(2019/10/15)
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- Design, synthesis and biological evaluation of a series of novel GPR40 agonists containing nitrogen heterocyclic rings
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A novel series of GPR40 agonists is designed by introducing nitrogen-containing heterocyclic ring at the terminal phenyl ring of TAK-875 with the aim of decreasing its lipophilicity. Three different β-substituted phenylpropionic acids were investigated as the acidic components. A total of 34 compounds have been synthesized, among which, compound 30 exhibited comparable GPR40 agonistic activity in vitro with TAK-875 and relatively lower lipophilicity through calculation (30, EC50 = 1.2 μM, cLogP = 1.3; TAK-875: EC50 = 5.1 μM, cLogP = 3.4). Moreover, compound 30 was able to enhance the insulin secretion of primary islets isolated from normal ICR mice and showed no obvious inhibition against cytochromes P450 in vitro. In vivo, compound 30 exhibited efficacy in oral glucose tolerance test (oGTT) in normal ICR mice.
- Sun, Zhaozhu,Zhou, Tian,Pan, Xuan,Yang, Ying,Huan, Yi,Xiao, Zhiyan,Shen, Zhufang,Liu, Zhanzhu
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supporting information
p. 3050 - 3056
(2018/08/11)
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- Rapid Access to Thiolactone Derivatives through Radical-Mediated Acyl Thiol-Ene and Acyl Thiol-Yne Cyclization
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A new synthetic approach to thiolactones that employs an efficient acyl thiol-ene (ATE) or acyl thiol-yne (ATY) cyclization to convert unsaturated thiocarboxylic acid derivatives into thiolactones under very mild conditions is described. The high overall yields, fast kinetics, high diastereoselectivity, excellent regiocontrol, and broad substrate scope of these reaction processes render this a very useful approach for diversity-oriented synthesis and drug discovery efforts. A detailed computational rationale is provided for the observed regiocontrol.
- McCourt, Ruairi O.,Dénès, Fabrice,Sanchez-Sanz, Goar,Scanlan, Eoin M.
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supporting information
p. 2948 - 2951
(2018/05/28)
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- Heterocyclic compound
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The present invention relates to compound (I) or a salt thereof which has a ROR γ t inhibitory action. wherein each symbol is as defined in the specification.
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Paragraph 1173
(2016/10/08)
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- HETEROCYCLIC COMPOUNDS AND THEIR USE AS RETINOID-RELATED ORPHAN RECEPTOR (ROR) GAMMA-T INHIBITORS
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Provided are heterocyclic compounds having a RORγt inhibitory action represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
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Paragraph 0330
(2016/01/25)
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- Development of a large scale asymmetric synthesis of the glucocorticoid agonist BI 653048 BS H3PO4
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The development of a large scale synthesis of the glucocorticoid agonist BI 653048 BS H3PO4 (1·H3PO4) is presented. A key trifluoromethyl ketone intermediate 22 containing an N-(4-methoxyphenyl)ethyl amide was prepared by an enolization/bromine-magnesium exchange/electrophile trapping reaction. A nonselective propargylation of trifluoromethyl ketone 22 gave the desired diastereomer in 32% yield and with dr = 98:2 from a 1:1 diastereomeric mixture after crystallization. Subsequently, an asymmetric propargylation was developed which provided the desired diastereomer in 4:1 diastereoselectivity and 75% yield with dr = 99:1 after crystallization. The azaindole moiety was efficiently installed by a one-pot cross coupling/indolization reaction. An efficient deprotection of the 4-methoxyphenethyl group was developed using H3PO4/anisole to produce the anisole solvate of the API in high yield and purity. The final form, a phosphoric acid cocrystal, was produced in high yield and purity and with consistent control of particle size.
- Reeves, Jonathan T.,Fandrick, Daniel R.,Tan, Zhulin,Song, Jinhua J.,Rodriguez, Sonia,Qu, Bo,Kim, Soojin,Niemeier, Oliver,Li, Zhibin,Byrne, Denis,Campbell, Scot,Chitroda, Ashish,Decroos, Phil,Fachinger, Thomas,Fuchs, Victor,Gonnella, Nina C.,Grinberg, Nelu,Haddad, Nizar,Jaeger, Burkhard,Lee, Heewon,Lorenz, Jon C.,Ma, Shengli,Narayanan, Bikshandarkoil A.,Nummy, Larry J.,Premasiri, Ajith,Roschangar, Frank,Sarvestani, Max,Shen, Sherry,Spinelli, Earl,Sun, Xiufeng,Varsolona, Richard J.,Yee, Nathan,Brenner, Michael,Senanayake, Chris H.
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p. 3616 - 3635
(2013/06/04)
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- SUBSTITUTED HETEROCYCLIC COMPOUNDS
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The present invention relates to substituted heterocyclic compounds of Formula I or XI: or pharmaceutically acceptable salts or N-oxides or quaternary ammonium salts thereof wherein constituent members are provided hereinwith, as well as their compositions and methods of use, which are histamine II4 receptor inhibitors useful in the treatment of histamine II4 receptor-associated conditions or diseases or disorders including, for example, inflammatory diseases or disorders, pruritus, and pain.
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Page/Page column 99-100
(2010/10/03)
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- SYNTHESIS OF CERTAIN TRIFLUOROMETHYL KETONES
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A process for synthesis of a compound of Formula (X) wherein R1 is an aryl group substituted with one to three substituent groups, wherein each substituent group of R1 is independently C1-C5 alkyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, halogen, carboxy, cyano, or trifluoromethyl, wherein each substituent group of R1 is optionally independently substituted with one to three substituents selected from C1-C3 alkyl, C1-C3 alkoxy, phenyl, and alkoxyphenyl; and R2 and R3 are each independently C1-C5 alkyl.
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Page/Page column 13-14
(2010/12/29)
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- GLUCOCORTICOID MIMETICS, METHODS OF MAKING THEM, PHARMACEUTICAL COMPOSITIONS, AND USES THEREOF
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Compounds of Formula I wherein R1, R2, X, and Y are as defined herein, or a tautomer, optical isomer, prodrug, co-crystal, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.
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Page/Page column 98-99
(2009/12/28)
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- Process for preparing C7 intermediates and their use in the preparation on N-substituted pyrrole derivatives
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The present invention relates to a process for preparing C7 intermediates and their use in the preparation of pyrrole derivatives of a class that is effective at inhibiting the biosynthesis of cholesterol in humans, and more particularly to improved synthetic methods for preparing 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids. The invention further relates to intermediates in this process.
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Page/Page column 5
(2010/11/28)
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- Process for preparing C5 products and their use for Atorvastatin synthesis
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The present invention relates to a process for preparing C5 intermediates and their use in the preparation of pyrrole derivatives of a class that is effective at inhibiting the biosynthesis of cholesterol in humans, and more particularly to improved synthetic methods for preparing 3,5-dihydroxy-7-pyrrol-1-yl heptanoic acids from 1,4-diketo starting materials. The invention further relates to intermediates in this process
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Page/Page column 5; 17
(2010/11/23)
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- CYCLIC CARBOTHIOIC ACID DERIVATIVES
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A compound or a mixture of compounds comprising an aromachernical compound of the formula: (I) wherein: R is a straight or branched chain, saturated or unsaturated hydrocarbyl group; preferably, alkyl or alkenyl, having 1-8 carbon atoms; R1 is a straight or branched chain, saturated or unsaturated hydrocarbyl group; preferably, alkyl or alkenyl, having 1-8 carbon atoms; x is an integer from I to 8, and y is an integer from o to 4. as well as compositions, products, preparations or articles having improved aroma, fragrance or odor characteristics containing as active ingredient such compound or mixture of compounds.
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- Convenient Access to Polysubstituted 1-Indanones by Sc(OTf) 3-Catalyzed Intramolecular Friedel-Crafts Acylation of Benzyl Meldrum's Acid Derivatives
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(Matrix presented) The intramolecular Friedel-Crafts acylation of benzyl Meldrum's acids is catalyzed by Sc(OTf)3 under mild reaction conditions. Several polysubstituted 1-indanones have been prepared.
- Fillion, Eric,Fishlock, Dan
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p. 4653 - 4656
(2007/10/03)
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- Mn(III)-based oxidative free-radical cyclizations of alkenyl Meldrum's acids
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Oxidative cyclization of unsaturated Meldrum's acids can be carried out at temperatures as low as -30°C. The rate-determining step is cyclization of the enolate to the alkene (11 to 14 and 15) rather than enolization, which is the rate-determining step with dimethyl 4-pentenylmalonate (1). While cyclization of 1 gives mainly cyclopentanes, cyclization of Meldrum's acids provides a versatile route to cyclohexenes.
- Snider, Barry B.,Smith, Rachel B.
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- A regiospecific synthesis of 3,3,6-trimethylindan-1-one
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A novel, regiospecific synthesis of 3,3,6-trimethylindan1-one (5) was achieved. The route to 5 was 6 steps and proceeded in 27% overall yield.
- Vogt,Molino,Robichaud
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p. 679 - 684
(2007/10/03)
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- REACTION OF TRIMETHYLSILYL DERIVATIVES WITH MELDRUM'S ACID : A NEW AND EASY MONOFUNCTIONALIZATION OF MALONIC ACID
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Treament of Meldrum's acid with silylated derivatives (amines, lactams or alcohols) yields very easily monofunctionalized malonic silyl esters.Hydrolysis of these silyl esters leads to the corresponding monoacids with a very good yield.
- Rigo, B.,Fasseur, D.,Cauliez, P.,Couturier, D.
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p. 3073 - 3076
(2007/10/02)
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- A NOVEL SOLVOLYTIC REARRANGEMENT OF 2,2-DIMETHYL-5-(1-BROMOMETHYLETHYLIDENE)-1,3-DIOXANE-4,6-DIONE
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Treatment of the title compound under basic aqueous conditions leads to 2,2-dimethyl-5-(2-ketopropyl)-1,3-dioxane-4,6-dione; the structure and mechanism of formation of this compound is described.
- Hunter, Norman R.,Green, Nancy A.,McKinnon, David M.
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p. 4589 - 4592
(2007/10/02)
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