- Gold-Catalyzed Cyclization of 2-Alkynylaldehyde Cyclic Acetals via Hydride Shift for the Synthesis of Indenone Derivatives
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An efficient gold-catalyzed cyclization of 2-alkynylaldehyde cyclic acetals has been developed for the synthesis of indenone derivatives. A wide variety of functionalized indenone derivatives can be obtained in good-to-excellent yields. HMBC and NOESY NMR analyses and mechanistic elucidation experiments revealed that the cyclization occurs via a 1,5-H shift. The cyclic acetal group promoted the 1,5-H shift by activating the benzylic C-H bond and preventing the migration of the alkoxy group by tethering both alkoxy groups.
- Yamada, Tsuyoshi,Park, Kwihwan,Tachikawa, Takumu,Fujii, Akiko,Rudolph, Matthias,Hashmi, A. Stephen K.,Sajiki, Hironao
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supporting information
p. 1883 - 1888
(2020/03/03)
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- DIARYLTHIOHYDANTOIN COMPOUND AS ANDROGEN RECEPTOR ANTAGONIST
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The present application belongs to the field of medicine. In particular, the present application relates to a diarylthiohydantoin compound as an androgen receptor antagonist or a pharmaceutically acceptable salt thereof, a preparation method of the same, a pharmaceutical composition comprising the compound, and a use thereof in treating a cell proliferative disease mediated by androgen. The compound of the present application has good antagonistic effect on androgen receptor and exhibits excellent antitumor effect.
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Paragraph 0679-0681
(2020/07/07)
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- Sequential Assembly of Morita-Baylis-Hillman Carbonates and Activated ortho-Vinylbenzaldehydes to Construct Chiral Methanobenzo[7]annulenone Frameworks
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The α-regioselective asymmetric [3 + 2] annulation reaction of Morita-Baylis-Hillman carbonates from isatins and activated ortho-vinylbenzaldehyses was developed by the catalysis of a chiral tertiary amine. The sequential N-heterocyclic carbene-mediated intramolecular Stetter reaction was conducted to finally furnish the bridged 5,8-methanobenzo[7]annulen-9-one architectures incorporating a spirooxindole motif with excellent stereoselectivity.
- Jiang, Bo,Xiao, Ben-Xian,Ouyang, Qin,Liang, Hua-Ping,Du, Wei,Chen, Ying-Chun
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supporting information
(2019/05/08)
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- Palladium-catalyzed ortho-C(sp2)[sbnd]H bromination of benzaldehydes via a monodentate transient directing group strategy
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A facile and efficient monodentate transient directing group strategy was developed to enable the palladium-catalyzed ortho-C(sp2)[sbnd]H bromination of benzaldehydes. A broad scope of benzaldehydes were transformed into the desired products by employing 2-amino-5-chlorobenzotrifluoride as a monodentate transient directing group, demonstrating good functional group tolerance. Mild reaction conditions and no requirement for a silver salt are also features of this strategy.
- Yong, Qiyun,Sun, Bing,Zhang, Fang-Lin
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supporting information
(2019/11/03)
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- Method for preparing 3,5-disubstituted oxadiazole compound
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The invention discloses a method for preparing a 3,5-disubstituted oxadiazole compound N-((3-(2-bromo-5-nitrophenyl)-1,2,4-oxadiazole-5-yl)methyl)ethylamine. 4-nitrobromobenzene used as a starting material undergoes hydroformylation, oximation, eliminatio
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Paragraph 0024-0026
(2019/04/30)
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- Enantioselective, Catalytic Vicinal Difluorination of Alkenes
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The enantioselective, catalytic vicinal difluorination of alkenes is reported by II/IIII catalysis using a novel, C2-symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArIIIIF2 species is enabled by Selectfluor oxidation and addition of an inexpensive HF–amine complex. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of Br?nsted acidity. Selectivity reversal from the 1,1-difluorination pathway (geminal) to the desired 1,2-difluorination (vicinal) is disclosed (>20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF3 unit that is pervasive in drug discovery (20 examples, up to 94:06 e.r.). An achiral variant of the reaction is also presented using p-TolI (up to >95 % yield).
- Scheidt, Felix,Sch?fer, Michael,Sarie, Jér?me C.,Daniliuc, Constantin G.,Molloy, John J.,Gilmour, Ryan
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supporting information
p. 16431 - 16435
(2018/11/23)
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- Organocatalytic regiospecific synthesis of 1H-indene-2-carbaldehyde derivatives: suppression of cycloolefin isomerisation by employing sterically demanding catalysts
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The regiospecific synthesis of 1H-indene-2-carbaldehyde derivatives was achieved through transition-metal-free, reductive cyclisation of ortho-formyl trans-cinnamaldehydes with Hantzsch ester in the presence of an aminocatalyst. In particular, cycloolefin isomerisation of the resulting products could be inhibited efficiently by the introduction of a sterically demanding stereo-defined aminocatalyst.
- Mao, Hui,Kim, Dong Wan,Shin, Hun Yi,Song, Choong Eui,Yang, Jung Woon
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supporting information
p. 1355 - 1362
(2017/02/15)
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- Discovery of a Highly Potent, Selective, and Orally Bioavailable Macrocyclic Inhibitor of Blood Coagulation Factor VIIa-Tissue Factor Complex
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Inhibitors of the tissue factor (TF)/factor VIIa complex (TF-FVIIa) are promising novel anticoagulants which show excellent efficacy and minimal bleeding in preclinical models. Starting with an aminoisoquinoline P1-based macrocyclic inhibitor, optimizatio
- Zhang, Xiaojun,Glunz, Peter W.,Johnson, James A.,Jiang, Wen,Jacutin-Porte, Swanee,Ladziata, Vladimir,Zou, Yan,Phillips, Monique S.,Wurtz, Nicholas R.,Parkhurst, Brandon,Rendina, Alan R.,Harper, Timothy M.,Cheney, Daniel L.,Luettgen, Joseph M.,Wong, Pancras C.,Seiffert, Dietmar,Wexler, Ruth R.,Priestley, E. Scott
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p. 7125 - 7137
(2016/08/24)
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- Tandem Pd-catalyzed C-C coupling/recyclization of 2-(2-bromoaryl)cyclopropane-1,1-dicarboxylates with primary nitro alkanes
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The first successful synthesis of 1H-2,3-benzoxazine 3-oxides has been described. The efficiency of the approach is provided by the C-C-coupling of 2-(2-bromoaryl)cyclopropane-1,1-dicarboxylates with primary nitroalkanes catalyzed by Pd(dba)2/JohnPhos system followed by in situ recyclization of the intermediates. Several representative transformations allowing selective modification of the nitronate as well as malonate functionalities in the resulting compounds are demonstrated.
- Mikhaylov, Andrey A.,Dilman, Alexander D.,Novikov, Roman A.,Khoroshutina, Yulia A.,Struchkova, Marina I.,Arkhipov, Dmitry E.,Nelyubina, Yulia V.,Tabolin, Andrey A.,Ioffe, Sema L.
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supporting information
p. 11 - 14
(2015/12/23)
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- Synthesis and P1′ SAR exploration of potent macrocyclic tissue factor-factor VIIa inhibitors
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Selective tissue factor-factor VIIa complex (TF-FVIIa) inhibitors are viewed as promising compounds for treating thrombotic disease. In this contribution, we describe multifaceted exploratory SAR studies of S1′-binding moieties within a macrocyclic chemotype aimed at replacing cyclopropyl sulfone P1′ group. Over the course of the optimization efforts, the 1-(1H-tetrazol-5-yl)cyclopropane P1′ substituent emerged as an improved alternative, offering increased metabolic stability and lower clearance, while maintaining excellent potency and selectivity.
- Ladziata, Vladimir (Uladzimir),Glunz, Peter W.,Zou, Yan,Zhang, Xiaojun,Jiang, Wen,Jacutin-Porte, Swanee,Cheney, Daniel L.,Wei, Anzhi,Luettgen, Joseph M.,Harper, Timothy M.,Wong, Pancras C.,Seiffert, Dietmar,Wexler, Ruth R.,Priestley, E. Scott
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p. 5051 - 5057
(2016/10/05)
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- SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS
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The present invention relates to novel substituted bridged urea compounds, corresponding related analogs, pharmaceutical compositions and methods of use thereof. Sirtuin-modulating compounds of the present invention may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders, which include, but are not limited to, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. The present invention also related to compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Paragraph 0881; 0882
(2015/06/10)
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- PYRIMIDOPYRIMIDINONES USEFUL AS WEE-1 KINASE INHIBITORS
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The present invention relates to compounds that are useful as inhibitors of the activity of Wee-1 kinase. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in the treatment of cancer and methods of treating cancer.
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Page/Page column 303
(2015/07/07)
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- Simple, copper(I)-catalyzed oxidation of benzylic/allylic alcohols to carbonyl compounds: Synthesis of functionalized cinnamates in one pot
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An environmentally benign [Cu(I)]-catalyzed oxidation of activated (benzylic/allylic) alcohols to the corresponding carbonyl compounds is presented. Interestingly, the reaction was also compatible with benzylic alcohols containing ortho-bromo substituents on the aromatic ring without competing with the expected intermolecular Buchwald coupling. Significantly, the catalytic system enables the synthesis of cinnamate-esters in a sequential domino one-pot fashion via oxidation followed by Wittig-Horner protocol. Copyright
- Reddy, Alavala Gopi Krishna,Mahendar, Lodi,Satyanarayana, Gedu
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supporting information
p. 2076 - 2087
(2014/07/07)
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- SUBSTITUTED BRIDGED UREA ANALOGS AS SIRTUIN MODULATORS
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Provided herein are novel substituted bridged urea and related analogs and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.
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Page/Page column 173-174
(2014/12/12)
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- Selective ortho -bromination of substituted benzaldoximes using Pd-catalyzed C-H activation: Application to the synthesis of substituted 2-bromobenzaldehydes
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Substituted 2-bromobenzaldehydes were synthesized from benzaldehydes using a three-step sequence involving a selective palladium-catalyzed ortho-bromination as the key step. O-Methyloxime serves as a directing group in this reaction. A rapid deprotection of substituted 2-bromobenzaldoximes afforded substituted 2-bromobenzaldehydes with good overall yields.
- Dubost, Emmanuelle,Fossey, Christine,Cailly, Thomas,Rault, Sylvain,Fabis, Frederic
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experimental part
p. 6414 - 6420
(2011/09/16)
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- Hydrogen-bonding catalysis and inhibition by simple solvents in the stereoselective kinetic epoxide-opening spirocyclization of glycal epoxides to form spiroketals
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Mechanistic investigations of a MeOH-induced kinetic epoxide-opening spirocyclization of glycal epoxides have revealed dramatic, specific roles for simple solvents in hydrogen-bonding catalysis of this reaction to form spiroketal products stereoselectively with inversion of configuration at the anomeric carbon. A series of electronically tuned C1-aryl glycal epoxides was used to study the mechanism of this reaction based on differential reaction rates and inherent preferences for SN2 versus SN1 reaction manifolds. Hammett analysis of reaction kinetics with these substrates is consistent with an SN2 or SN2-like mechanism (ρ = -1.3 vs ρ = -5.1 for corresponding SN1 reactions of these substrates). Notably, the spirocyclization reaction is second-order dependent on MeOH, and the glycal ring oxygen is required for second-order MeOH catalysis. However, acetone cosolvent is a first-order inhibitor of the reaction. A transition state consistent with the experimental data is proposed in which one equivalent of MeOH activates the epoxide electrophile via a hydrogen bond while a second equivalent of MeOH chelates the side-chain nucleophile and glycal ring oxygen. A paradoxical previous observation that decreased MeOH concentration leads to increased competing intermolecular methyl glycoside formation is resolved by the finding that this side reaction is only first-order dependent on MeOH. This study highlights the unusual abilities of simple solvents to act as hydrogen-bonding catalysts and inhibitors in epoxide-opening reactions, providing both stereoselectivity and discrimination between competing reaction manifolds. This spirocyclization reaction provides efficient, stereocontrolled access to spiroketals that are key structural motifs in natural products.
- Wurst, Jacqueline M.,Liu, Guodong,Tan, Derek S.
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supporting information; experimental part
p. 7916 - 7925
(2011/07/08)
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- Versatile synthesis of isoquinolines and isochromenes by Pd-catalyzed oxidative carbonylation of (2-alkynyl)benzylideneamine derivatives
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Isoquinoline-4-carboxylic esters 3 and isochromene-4-carboxylic esters 4 have been conveniently prepared by direct PdI2-catalyzed oxidative heterocyclization/alkoxycarbonylation of readily available (2- alkynylbenzylidene)amine derivatives. In particular, (2-alkynylbenzylidene) (tert-butyl)amines 2 selectively afforded isoquinoline derivatives 3 by N-cyclization, whereas N-(2-alkynylbenzylidene)-N′-phenylhydrazines 5 led to the formation of isochromenes 4 through O-cyclization ensuing from water attack on the imino group of the substrate. Reactions were carried out in alcoholic solvents at 80-100 °C and under 20-80 atm (at 25 °C) of a 4:1 mixture of CO/air, in the presence of PdI2 (2-10 mol-%) in conjunction with KI (KI/PdI2 molar ratio = 10). In the case of imines 2, the use of a dehydration agent, such as trialkyl orthoformate, was necessary to obtain satisfactory yields of isoquinolines 3.
- Gabriele, Bartolo,Veltri, Lucia,Maltese, Vito,Spina, Rosella,Mancuso, Raffaella,Salerno, Giuseppe
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experimental part
p. 5626 - 5635
(2011/11/29)
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- MACROCYCLIC FACTOR VIIA INHIBITORS USEFUL AS ANTICOAGULANTS
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The present invention relates generally to novel macrocycles of Formula (I) or stereoisomers, tautomers, pharmaceutically acceptable salts, solvates, or prodrugs thereof, wherein the variables A, B, C, D, L, M, W, Z1, Z2, Z3, Z4, R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 are as defined herein. These compounds are selective inhibitors of factor VIIa which can be used as medicaments.
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Page/Page column 106
(2008/12/07)
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- Palladium-catalyzed carbonylative cyclization of Baylis-Hillman adducts. An efficient approach for the stereoselective synthesis of 3-alkenyl phthalides
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A palladium-mediated carbonylative cyclization reaction of Baylis-Hillman adducts is disclosed. This simple, efficient and straightforward sequence leads to the formation of an array of 3-alkenylphthalides with different substitution patterns on the aromatic ring, with good chemical yields and selectivities.
- Coelho, Fernando,Veronese, Demetrius,Pavam, Cesar H.,de Paula, Vanderlei I.,Buffon, Regina
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p. 4563 - 4572
(2007/10/03)
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- Fused cycloheptane and fused azacycloheptane compounds and their methods of use
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The invention comprises novel compounds that are effective in the prophylaxis and treatment of diseases, such as integrin receptors mediated diseases, in particular, diseases or conditions mediated by integrin receptors, such as αvβ3, αvβ5, αvβ6and the like. The invention encompasses novel compounds, pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of such diseases and disorders. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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- Design and synthesis of a conformationally rigid mimic of the dihydropyrimidine calcium channel modulator SQ 32,926
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A conformationally rigid polyheterocycle (3) which mimics the putative receptor-bound conformation of dihydropyridine-type calcium channel modulators is prepared in a seven-step reaction sequence based on a Biginelli-type cyclocondensation reaction.
- Jauk, Birgit,Pernat, Tetiana,Kappe, C. Oliver
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p. 227 - 239
(2007/10/03)
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- N-substituted 3,4,5,6-tetrahydrophthalimides and their intermediates
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N-substituted 3,4,5,6-tetrahydrophthalimides and their intermediates of the general formula I STR1 where A is --NO2, --NH2 or STR2 corresponding to the compounds Ia, Ib and Ic, B is --CH2 --, --CH2 --CHR1/
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