- Palladium-Catalyzed Distal m-C-H Functionalization of Arylacetic Acid Derivatives
-
Herein, we present m-C-H olefination on derivatives of phenylacetic acids by tethering with a simple nitrile-based template through palladium catalysis. Notably, the versatility of the method is evaluated with a wide range of phenylacetic acid derivatives for obtaining the meta-olefination products in fair to excellent yields with outstanding selectivities under mild conditions. Significantly, the present strategy is successfully exemplified for the synthesis of drugs/natural product analogues (naproxen, ibuprofen, paracetamol, and cholesterol).
- Srinivas, Dasari,Satyanarayana, Gedu
-
supporting information
p. 7353 - 7358
(2021/10/01)
-
- Synthesis of Tertiary Benzylic Nitriles via Nickel-Catalyzed Markovnikov Hydrocyanation of α-Substituted Styrenes
-
The Markovnikov hydrocyanation of α-substituted styrenes enables the synthesis of tertiary benzylic nitriles under nickel catalysis. The Lewis-acid-free transformation features an unprecedented functional groups tolerance, including the-OH and-NH2 groups. A broad range of tertiary benzylic nitriles were obtained in good to excellent yields. In addition, an asymmetric version of this reaction was preliminarily investigated.
- Xing, Yidan,Yu, Rongrong,Fang, Xianjie
-
p. 1008 - 1012
(2020/02/04)
-
- Cobalt-catalyzed C[sbnd]H activation/C[sbnd]O formation: Synthesis of benzofuranones
-
Herein, C[sbnd]H activation/C[sbnd]O formation reaction using novel cobalt catalytic system is reported. This reaction was given benzofuranones in moderate to excellent yields at room-temperature under air reaction conditions. The introduced strategy is efficient and low-cost method to synthesized benzofuranones from α,α-disubstitution acetic acid.
- Hajipour, Abdol R.,Khorsandi, Zahra
-
-
- EP300/CREBBP INHIBITOR
-
The present invention provides a compound having excellent histone acetyltransferase inhibitory activity against EP300 and/or CREBBP, or a pharmacologically acceptable salt thereof. The compound is represented by the following formula (1) or a pharmacologically acceptable salt thereof: wherein ring Q1, ring Q2, R1, R2, R3 and R4 respectively have the same meanings as defined in the specification.
- -
-
Paragraph 0344; 0345; 0372; 0373
(2020/05/30)
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- N2-(2-METHOXYPHENYL)PYRIMIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION FOR CANCER PREVENTION OR TREATMENT CONTAINING SAME AS ACTIVE INGREDIENT
-
The present invention relates to a N2-(2-methoxyphenyl)pyrimidine derivative, a preparation method thereof, and a pharmaceutical composition for the prevention or treatment of cancer comprising the same as an active ingredient. The N2-(2-methoxyphenyl)pyrimidine derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention is very effective in suppressing anaplastic lymphoma kinase (ALK) activity and as a result it can improve the effectiveness of treatment on cancer cells having anaplastic lymphoma kinase (ALK) fusion proteins such as EML4-ALK and NPM-ALK, so that it can be effectively used as a pharmaceutical composition for preventing or treating cancer.
- -
-
Paragraph 0302; 0303; 0304; 0305; 0306
(2018/05/03)
-
- Synthesis of indolines by copper-mediated intramolecular aromatic C-H amination
-
A Cu(OAc)2-mediated intramolecular aromatic C-H amination proceeds with the aid of a picolinamide-type bidentate coordination group to deliver the corresponding indolines in good yields. The reaction occurs smoothly even under noble-metal-free conditions, and in some cases the use of an MnO2 terminal oxidant renders the process catalytic in Cu. The mild oxidation aptitude of Cu(OAc)2 and/or MnO2 accommodates the formation of electron-rich thiophene-and indole-fused indoline analogues. The Cu-based system can provide an effective approach to various indolines of potent interest in pharmaceutical and medicinal chemistry.
- Takamatsu, Kazutaka,Hirano, Koji,Satoh, Tetsuya,Miura, Masahiro
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p. 3242 - 3249
(2015/03/30)
-
- A biomimetic catalytic aerobic functionalization of phenols
-
The importance of aromatic C-O, C-N, and C-S bonds necessitates increasingly efficient strategies for their formation. Herein, we report a biomimetic approach that converts phenolic C-H bonds into C-O, C-N, and C-S bonds at the sole expense of reducing dioxygen (O2) to water (H 2O). Our method hinges on a regio- and chemoselective copper-catalyzed aerobic oxygenation to provide ortho-quinones. ortho-Quinones are versatile intermediates, whose direct catalytic aerobic synthesis from phenols enables a mild and efficient means of synthesizing polyfunctional aromatic rings. The direct approach: Polyfunctional aromatic rings have been generated by direct functionalization of C-H bonds to C-O, C-N, and C-S bonds at the sole expense of reducing O2 to H2O. The method hinges on a regio- and chemoselective, copper-catalyzed aerobic oxygenation of phenols to provide ortho-quinones (see scheme), thus mimicking the ubiquitous biosynthetic pathway of melanogenesis.
- Esguerra, Kenneth Virgel N.,Fall, Yacoub,Lumb, Jean-Philip
-
supporting information
p. 5877 - 5881
(2014/06/10)
-
- Carbon-based leaving group in substitution reactions: Functionalization of sp3-hybridized quaternary and tertiary benzylic carbon centers
-
Lewis acid promoted substitution reactions employing Meldrum's acid and 5-methyl Meldrum's acid as carbon-based leaving groups are described which transform unstrained quaternary and tertiary benzylic Csp 3-Csp3 bonds into Csp3-X bonds (X = C, H, N). Importantly, this reaction has a broad scope in terms of both suitable substrates and nucleophiles with good to excellent yields obtained (typically >90%).
- Mahoney, Stuart J.,Lou, Tiantong,Bondarenko, Ganna,Fillion, Eric
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p. 3474 - 3477
(2012/09/05)
-
- Effects of various bases on acid-catalyzed amination of 2-chloro-5-ethylpyrimidine: Synthesis of PPARpan agonist GW693085
-
Figure presented A unique buffering effect of various bases, i-Pr 2NEt and CaCO3 in particular, was observed for the acid-catalyzed chloro displacement of 2-chloro-5-ethylpyrimidine with a 2-methyl-2-phenylpropanamine. The use of the
- Glover, Bobby N.,Jones, Lynda A.,Johnson, Byron S.,Millar, Alan,Osterhout, Martin H.,Xie, Shiping
-
experimental part
p. 3904 - 3907
(2010/07/05)
-
- TETRAHYDROISOQUINOLINES, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND THEIR USE IN THERAPY
-
The present invention relates to tetrahydroisoquinoline of the formula (I) or a physiologically tolerated salt thereof. The invention relates to pharmaceutical compositions comprising such tetrahydroisoquinolines, and the use of such tetrahydroisoquinolin
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-
Page/Page column 123
(2009/10/30)
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- CDK INHIBITORS CONTAINING A ZINC BINDING MOIETY
-
The present invention relates to CDK inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The compounds of the invention may further act as HDAC inhibitors.
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-
Page/Page column 77
(2009/04/25)
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- Facile preparation of α-aryl nitriles by direct cyanation of alcohols with TMSCN under the catalysis of InX3
-
(Chemical Equation Presented) A convenient and efficient synthesis of α-aryl nitrites was developed by direct cyanation of alcohols with TMSCN under the catalysis of Lewis acid. Using 5-10 mol % of InBr3 as the catalyst, a variety of benzylic alcohols can be converted to the corresponding nitriles in 5-30 min with yields of 46-99%.
- Chen, Gang,Wang, Zheng,Wu, Jiang,Ding, Kuiling
-
supporting information; experimental part
p. 4573 - 4576
(2009/05/07)
-
- A COMBINATION OF NIACIN AND A PROSTAGLANDIN D2 RECEPTOR ANTAGONIST
-
The present invention is directed to a pharmaceutical composition comprising Niacin or a pharmaceutically acceptable salt, solvate or N-oxide thereof, or a nicotinic acid receptor agonist, and a compound of formula (I) as defined herein, or an N-oxide thereof, or an ester prodrug thereof, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, and its use for treating atherosclerosis, dyslipidemia, diabetes or a related condition while reducing substantial flushing.
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-
Page/Page column 128
(2008/06/13)
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- Synthesis of the C1-C15 fragment of apicularen A through a regioselective electron-transfer-initiated cyclization reaction
-
In this paper we report the preparation of the benzyltetrahydropyran fragment of the vacuolar ATPase inhibitor apicularen A through an oxidative cyclization protocol. In this reaction regioselective cleavage of one homobenzylic ether in the presence of another homobenzylic ether is achieved by selectively weakening one carbon-carbon σ-bond through substitution. This work demonstrates that oxidative fragmentation reactions can be used to generate stable cations selectively, even in the presence of other readily oxidized groups, provided that bond cleavage is sufficiently rapid following oxidation. Georg Thieme Verlag Stuttgart.
- Poniatowski, Alexander J.,Floreancig, Paul E.
-
p. 2291 - 2296
(2008/03/12)
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- 1,3-Diethynylallenes: Stable monomers, length-defined oligomers, asymmetric synthesis, and optical resolution
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A series of differently substituted 1,3-diethynylallenes (DEAs) have been synthesized, confirming that the previously introduced construction protocols tolerate a variety of functional groups. The new DEAs bear at least one polar group to facilitate enantiomer separations on chiral stationary phases and to allow further functionalization. They are thermally and environmentally stable compounds since bulky substituents next to the cumulene moiety suppress the tendency to undergo [2+2] cyclodimerization. A series of length-defined oligomers were obtained as mixtures of stereoisomers by oxidative coupling of a monomeric DEA under Glaser-Hay conditions. The electronic absorption data indicate a lack of extended π-electron conjugation across the oligomeric backbone due to the orthogonality of the allenic π-systems. Remarkably, even complex mixtures of stereoisomers only yield one single set of NMR signals, which underlines the low stereodifferentiation in acyclic allenoacetylenic structures. Optical resolution of DEAs represents an amazing challenge, and preliminary results on the analytical level are reported. Asymmetric synthesis by Pd-mediated SN2′-type cross-coupling of an alkyne to an optically pure bispropargylic precursor opens another promising route to optically active allenes with stereoselectivities currently reaching up to 78 % ee. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Ter Wiel, Matthijs K. J.,Odermatt, Severin,Schanen, Patrick,Seiler, Paul,Diederich, Francois
-
p. 3449 - 3462
(2008/02/12)
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- 2, 6-SUBSTITUTED-4-MONOSUBSTITUTEDAMINO-PYRIDIMIDINE AS PROSTAGLANDIN D2 RECEPTOR ANTAGONISTS
-
The present invention is directed a compound of Formula (I) as defined herein, a pharmaceutical composition comprising a pharmaceutically effective amount of one or more compounds according to Formula (I) in admixture with a pharmaceutically acceptable carrier, and a method of treating a patient suffering from a PGD2-mediated disorder including, but not limited to, allergic disease (such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma and food allergy), systemic mastocytosis, discorders accompanied by systemic mast cell activation, anaphylaxis shock, bronchoconstriction, bronchitis, urticaria, eczema, diseases accompanied by itch (such as atopic dermatitis and urticaria), diseases (such as cataract, retinal detachment, inflammation, infection and sleeping disorders) which is generated secondarily as a result of behavior accompanied by itch (such as scratching and beating), inflammation, chronic obstructive pulmonary diseases, ischemic reperfusion injury, cerebrovascular accident, chronic rheumatoid arthritis, pleurisy, ulcerative colitis and the like by administering to said patient a pharmaceutically effective amount of a compound according to Formula (I).
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Page/Page column 129
(2008/06/13)
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- Potent 4-amino-5-azaindole factor VIIa inhibitors
-
The 4-amino-5-azaindole as an amidino-benzimidazole replacement is described. A series of potent and selective analogs were discovered and showed desirable ex vivo efficacy as measured by PT.
- Hu, Huiyong,Kolesnikov, Aleksandr,Riggs, Jennifer R.,Wesson, Kieron E.,Stephens, Robin,Leahy, Ellen M.,Shrader, William D.,Sprengeler, Paul A.,Green, Michael J.,Sanford, Ellen,Nguyen, Margaret,Gjerstad, Erik,Cabuslay, Ronnel,Young, Wendy B.
-
p. 4567 - 4570
(2007/10/03)
-
- FACTOR VIIA INHIBITOR
-
The present invention relates to novel inhibitors of Factors VIIa, IXa, Xa, XIa, in particular Factor VIIa, pharmaceutical compositions comprising these inhibitors, and methods for using these inhibitors for treating or preventing thromboembolic disorders
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-
Page/Page column 23-24
(2010/02/15)
-
- DIARYL ETHERS AS OPIOID RECEPTOR ANTAGONIST
-
A compound of the formula (I) wherein the variables X1 to X10, R1 to R7 including R3', E, v, y, z, A and B are as described, or a pharmaceutically acceptable salt, solvate, enantiomer, racemate, diastereomer or mixtures thereof, useful for the treatment, prevention or amelioration of obesity and Related Diseases is disclosed.
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Page/Page column 108-109
(2008/06/13)
-
- A convenient ring formation of 3-aryl-2,2-dialkyl-2,3-dihydrobenzofurans from phenols and 2-aryl-2,2-dialkylacetaldehydes
-
A new and simple route for the preparation of 3-aryl-2,2-dialkyl-2,3- dihydrobenzofurans from phenols is described. In the presence of an acid catalyst phenols react with 2-aryl-2,2-dialkylacetaldehydes, prepared in good yield from 2-arylacetonitriles in 2 steps, to give 3-aryl-2,2-dialkyl-2,3- dihydrobenzofurans. Electron-donating substituents were required on the phenols in order to give 3-aryl-2,2-dialkyl-2,3-dihydrobenzofurans in good yield.
- Yamashita, Makoto,Ono, Yujirou,Tawada, Hiroyuki
-
p. 2843 - 2849
(2007/10/03)
-
- A General Method for the Direct α-Arylation of Nitriles with Aryl Chlorides
-
The long-standing challenge of developing a general method for the title methodology is met for a broad range of aryl chlorides through the use of bicyclic P(iBuNCH2CH2)3N (1) as a bulky electron-rich ligand for palladium (see scheme, dba = dibenzylideneacetone).
- You, Jingsong,Verkade, John G.
-
p. 5051 - 5053
(2007/10/03)
-
- P(i-BuNCH2CH2)3N: An efficient ligand for the direct α-arylation of nitriles with aryl bromides
-
A new catalyst system for the synthesis of α-aryl-substituted nitriles is reported. The bicyclic triaminophosphine P(i-BuNCH 2CH2)3N (1b) serves as an efficient and versatile ligand for the palladium-catalyzed direct α-arylation of nitriles with aryl bromides. Using ligand 1b, ethyl cyanoacetate and primary as well as secondary nitriles are efficiently coupled with a wide variety of aryl bromides possessing electron-rich, electron-poor, electron-neutral, and sterically hindered groups.
- You, Jingsong,Verkade, John G.
-
p. 8003 - 8007
(2007/10/03)
-
- HPPARS ACTIVATORS
-
Compounds of formula (1) or a pharmaceutically acceptable salt, solvate, acid isostere, or hydrolyzable ester thereof, are disclosed. Methods of making and using the compounds are also disclosed. In particular methods for treating diseases or conditions a
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-
Page/Page column 53
(2010/02/07)
-
- Synthesis, characterization, and reactivity of arylpalladium cyanoalkyl complexes: Selection of catalysts for the α-arylation of nitriles
-
A new coupling process, the palladium-catalyzed α-arylation of nitriles, was developed by exploring the structure and reactivity of arylpalladium cyanoalkyl complexes. Complexes of 1,2-bis(diphenylphosphino)benzene (DPPBz), 1,1′-bis(di-i-propylphosphino)ferrocene (DiPrPF), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (BINAP), and diphenylethylphosphine (PPh2Et) were prepared. Coordination to palladium through the α-carbon was observed for DPPBz-ligated complexes and for complexes of primary and benzylic nitrile anions. However, the anion of isobutyronitrile was coordinated to palladium through the cyano-nitrogen when the complex was ligated by DiPrPF. The isobutyronitrile anion displaced a phosphine ligand to form a C,N-bridged dimer when generated from PPh2Et-ligated palladium. These results suggest that the nitrile anion preferentially coordinates to palladium through the carbon atom in the absence of steric effects. Thermolysis of the arylpalladium cyanoalkyl complexes led to reductive elimination that formed α-aryl nitriles. The high yields and short reaction times observed for BINAP-ligated complexes suggested that BINAP-ligated palladium catalysts might be appropriate for the arylation of nitriles. Initial results on a palladium-catalyzed process for the direct coupling of aryl bromides and primary, benzylic, and secondary nitrile anions to form α-aryl nitriles in good yields are reported. Copyright
- Culkin, Darcy A.,Hartwig, John F.
-
p. 9330 - 9331
(2007/10/03)
-
- Process for preparing benzylnitriles
-
A process is described for preparing an aromatic compound substituted by a tertiary nitrile of Formula (1.0.0): comprising treating a substituted aromatic compound of Formula (2.0.0): with a secondary nitrile of Formula (3.0.0): in the presence of a base having a pKanumerical value in the range of from about 17 to about 30, provided that the difference in pKanumerical values between said base and the corresponding tertiary nitrile of Formula (3.0.0) is no more than about 6; in an aprotic solvent having a dielectric constant (∈) of less than about 20; and at a reaction temperature in the range of from about 0° C. to about 120° C.; whereby there is formed said tertiary-nitrile-substituted aromatic compound final product of Formula (1.0.0); wherein the constituent parts W1, W2, W3, W4, and W5; and the substituent moieties R1, R2, R3, R4, R5, R6, and R7in the compounds of Formulas (1.0.0), (2.0.0) and (3.0.0) are selected from known organic groups and radicals as further detailed in the instant specification.
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-
-
- 3-[5-substituted benzyl)amino]-2-phenylpiperidines as substance P antagonists
-
This invention provides a compound of the formula: STR1 and its pharmaceutically acceptable salts, wherein R 1 is C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, halo C 1 -C 6 alkyl or terahydropyranyl, having one or more substituents selected from cyano, 1,3-thiazolanyl, COOR 2, COR 2, OCOR 2, CONR 3 R 4, NR 3 R 4, NR 5 COR 3 and C.ident.CR 6, wherein R 2 is hydrogen or C 1 -C 4 alkyl, R 3 and R 4 are independently hydrogen, C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl, R 5 is C 1 -C 4 alkyl or C 3 -C 6 cycloalkyl and R 6 is hydrogen, halo, cyano, C 1 -C 6 alkyl, COOH, COO(C 1 -C 4 alkyl) or phenyl; X is C 1 -C 6 alkoxy or halo C 1 -C 6 alkoxy; and Ar is phenyl optionally substituted with halo.These compounds are useful in the treatment of allergic disorders, angiogenesis, gastrointestinal disorders, central nervous system disorders, inflammatory diseases, emesis, urinary incontinence, pain, migraine, sunburn, and diseases, disorders and adverse conditions caused by Helicobacter pylori, in a mammalian subject.
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-
-
- Application of electrogenerated triphenylmethyl anion as a base for alkylation of arylacetic esters and arylacetonitriles and isomerization of allylbenzenes
-
Phenylacetic esters and phenylacetonitriles were alkylated with alkyl halides, at the position α to an ester or nitrile, either at room temperature (20 deg C) or at -78 deg C, by making use of electrogenerated triphenylmethyl anion (trityl anion).Double-bond isomerization of allylbenzenes was also effectively accomplished by use of this electrogenerated base (EGB).
- Suzuki, Shohei,Kato, Mitsuko,Nakajima, Shoichi
-
p. 357 - 361
(2007/10/02)
-