- Stereoselective Synthesis of Chiral β-Fluoro α-Amino Acids via Pd(II)-Catalyzed Fluorination of Unactivated Methylene C(sp3)-H Bonds: Scope and Mechanistic Studies
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The synthesis of fluorinated complex molecules via direct C(sp3)-H fluorination is attractive yet remains challenging. Here we describe the Pd(II)-catalyzed fluorination of unactivated methylene C(sp3)-H bonds by an inner-sphere mech
- Zhang, Qi,Yin, Xue-Song,Chen, Kai,Zhang, Shuo-Qing,Shi, Bing-Feng
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- Nickel-catalyzed ortho-halogenation of unactivated (hetero)aryl C-H bonds with lithium halides using a removable auxiliary
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The first example of Ni-catalyzed halogenation of (hetero)aryl C-H bonds with lithium halides (LiX, X = Br, I, Cl) using PIP as a removable directing group is reported. This protocol provides an efficient access to ortho-halogenated (hetero)arenes with operational simplicity, good functional group tolerance, and large-scale synthesis.
- Zhan, Bei-Bei,Liu, Yan-Hua,Hu, Fang,Shi, Bing-Feng
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- Copper-Mediated Thiolation of Unactivated Heteroaryl C?H Bonds with Disulfides under Ligand- and Metal-Oxidant-Free Conditions
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Various sulfenylated heteroarenes were synthesized by a copper-mediated C?H thiolation, which was assisted by a 2-(pyridin-2-yl)isopropylamine (PIP-amine) directing group. The reaction features a broad substrate scope, good functional group tolerance, ligand- and metal-oxidant-free conditions, exceptional compatibility with aliphatic disulfides, and excellent yields, providing a highly efficient approach to the biologically important sulfenylated heteroarenes. (Figure presented.).
- Li, Ya,Liu, Yue-Jin,Shi, Bing-Feng
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- 5-FLUORONICOTINAMIDE DERIVATIVES AND USES THEREOF
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Provided herein is a compound of Formula (I), or pharmaceutically acceptable salt thereof, wherein R1, Y, X, and n are defined herein. Also provided herein are compositions comprising a compound of Formula (I) or pharmaceutically acceptable salt thereof, and methods of using a compound of Formula (I) or pharmaceutically acceptable salt thereof, e.g., in the treatment of heart disease.
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Paragraph 00495-00498
(2021/04/10)
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- HETEROCYCLIC COMPOUNDS AS ADENOSINE ANTAGONISTS
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Aminopyrazine compounds as modulators of an adenosine receptor are provided. The compounds may find use as therapeutic agents for the treatment of diseases mediated through a G-protein-coupled receptor signaling pathway and may find particular use in onco
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Paragraph 0405-0406
(2020/08/05)
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- Access to β-Ketonitriles through Nickel-Catalyzed Carbonylative Coupling of α-Bromonitriles with Alkylzinc Reagents
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Herein, we report a nickel-catalyzed carbonylative coupling of α-bromonitriles and alkylzinc reagents with near stoichiometric carbon monoxide to give β-ketonitriles in good yields. The reaction is catalyzed by a readily available and stable nickel(II) pincer complex. The developed protocol tolerates substrates bearing a variety of functional groups, which would be problematic or incompatible with previous synthetic methods. Additionally, we demonstrate the suitability of the method for carbon isotope labeling by the synthesis of 13C-labeled β-ketonitriles and their transformation into isotopically labeled heterocycles.
- Donslund, Aske S.,Neumann, Karoline T.,Corneliussen, Nicklas P.,Grove, Ebbe K.,Herbstritt, Domenique,Daasbjerg, Kim,Skrydstrup, Troels
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supporting information
p. 9856 - 9860
(2019/07/09)
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- Palladium-Catalyzed Electrochemical C-H Bromination Using NH4Br as the Brominating Reagent
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The palladium-catalyzed electrochemical C-H bromination of benzamide derivatives under divided cells is developed, in which NH4Br serves as a brominating reagent and electrolyte. The protocol avoids the use of chemical oxidants and provides an alternative method for the synthesis of aryl bromides.
- Yang, Qi-Liang,Wang, Xiang-Yang,Wang, Tong-Lin,Yang, Xiang,Liu, Dong,Tong, Xiaofeng,Wu, Xin-Yan,Mei, Tian-Sheng
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supporting information
p. 2645 - 2649
(2019/04/17)
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- Nickel-Catalyzed Sulfonylation of C(sp2)–H Bonds with Sodium Sulfinates
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The first nickel-catalyzed ortho-sulfonylation of C(sp2)–H bonds with sodium sulfinates directed by (pyridin-2-yl)isopropylamine (PIP-amine) is described. This strategy exhibits a broad substrate scope and good functional group tolerance with high monosulfonylation selectivity. Besides arenes and heteroarenes, the reaction can also be extended to alkenes, providing diverse diaryl and alkyl aryl sulfones in high yields. Furthermore, a plausible Ni(I)/Ni(III) mechanism is outlined based on our experimental results and related precedents. (Figure presented.).
- Liu, Shuang-Liang,Li, Xue-Hong,Zhang, Shu-Sheng,Hou, Sheng-Kai,Yang, Guang-Chao,Gong, Jun-Fang,Song, Mao-Ping
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supporting information
p. 2241 - 2246
(2017/07/07)
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- Palladium-Catalyzed Directed C(sp3)-H Arylation of Saturated Heterocycles at C-3 Using a Concise Optimization Approach
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Saturated heterocycles, such as THFs, pyrrolidines, piperidines and THPs, are essential components of many biologically active compounds. Examples of C-H functionalization on these important ring systems remain scarce, especially at unactivated positions. Here we report the development of conditions for the palladium-catalyzed stereoselective C(sp3)-H arylation at unactivated 3-positions of 5- and 6-membered N- and O-heterocycles with aminoquinoline directing groups. Subtle differences in substrate structures altered their reactivity significantly; and different conditions were required to achieve high yields in each case. Successful conditions were developed using a short empirical optimization approach to cover reaction space with a limited set of variables. Excellent cis-selectivity was achieved in all cases, except for the THP substrate where minor trans-products were formed through a different palladacyclic intermediate. Here, differences in reactivity and selectivity with other directing groups were examined.
- Affron, Dominic P.,Bull, James A.
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supporting information
p. 139 - 149
(2016/01/20)
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- Dual Role of Acetate in Copper(II) Acetate Catalyzed Dehydrogenation of Chelating Aromatic Secondary Amines: A Kinetic Case Study of Copper-Catalyzed Oxidation Reactions
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Copper(II) acetate is a frequent empirical choice of the copper source in copper(II)-mediated redox reactions. The effect of the acetate counterion appears crucial but has not been adequately investigated. Herein, we report that copper(II) acetate catalyz
- Sreenath, Kesavapillai,Yuan, Zhao,Macias-Contreras, Miguel,Ramachandran, Vasanth,Clark, Ronald J.,Zhu, Lei
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p. 3728 - 3743
(2016/08/19)
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- NITROGEN-CONTAINING SATURATED HETEROCYCLIC COMPOUND
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The present invention provides a compound represented by the following formula (I) or its pharmaceutically acceptable salt: [wherein, R1 represents optionally substituted C1-4 alkyl, n shows integer of 1 to 4, R2 represents optionally substituted C1-4 alkyl or hydrogen atom, R3 represents optionally substituted C1-4 alkyl, R4a, R4b, R4c, and R4d, similarly or differently, represent optionally substituted C6-14 aryl, optionally substituted C1-4 alkyl, or hydrogen atom and the like, A represents optionally substituted C6-14 aryl or optionally substituted 5 to 11 membered heteroaryl].
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Paragraph 0344
(2016/08/29)
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- Copper/silver-mediated direct ortho-ethynylation of unactivated (hetero)aryl C-H bonds with terminal alkyne
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A copper/silver-mediated oxidative ortho-ethynylation of unactivated aryl C-H bonds with terminal alkyne has been developed.The reaction uses the removable PIP directing group and features broad substrate scope, high functional-group tolerance, and compatibility with a wide range of heterocycles, providing an efficient synthesis of aryl alkynes. This procedure highlights the potential of copper catalysts to promote unique, synthetically enabling C-H functionalization reactions that lie outside of the current scope of precious metal catalysis.
- Liu, Yue-Jin,Liu, Yan-Hua,Yin, Xue-Song,Gu, Wen-Jia,Shi, Bing-Feng
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supporting information
p. 205 - 209
(2015/02/19)
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- Nickel-catalyzed thiolation of unactivated aryl C-H bonds: Efficient access to diverse aryl sulfides
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A nickel-catalyzed thiolation of unactivated C(sp2)-H bonds with disulfides employing the PIP directing group was described. This process uses a catalytic nickel catalyst and no metallic oxidants or cocatalysts are required. The reaction tolera
- Yan, Sheng-Yi,Liu, Yue-Jin,Liu, Bin,Liu, Yan-Hua,Shi, Bing-Feng
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supporting information
p. 4069 - 4072
(2015/03/30)
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- Copper-catalyzed ortho-halogenation of arenes and heteroarenes directed by a removable auxiliary
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Copper-catalyzed ortho-halogenation of C(sp2)-H bonds directed by a PIP directing group with NXS (X = Cl, Br, I) has been developed. The reaction is scalable and tolerates a broad range of functional groups and heteroarenes, providing an efficient access to halogenated arenes and heteroarenes.
- Li, Bo,Liu, Bin,Shi, Bing-Feng
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supporting information
p. 5093 - 5096
(2015/03/30)
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- Plasmepsin inhibitory activity and structure-guided optimization of a potent hydroxyethylamine-based antimalarial hit
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Antimalarial hit 1SR (TCMDC-134674) identified in a GlaxoSmithKline cell based screening campaign was evaluated for inhibitory activity against the digestive vacuole plasmepsins (Plm I, II, and IV). It was found to be a potent Plm IV inhibitor with no selectivity over Cathepsin D. A cocrystal structure of 1SR bound to Plm II was solved, providing structural insight for the design of more potent and selective analogues. Structure-guided optimization led to the identification of structurally simplified analogues 17 and 18 as low nanomolar inhibitors of both, plasmepsin Plm IV activity and P. falciparum growth in erythrocytes.
- Jaudzems, Kristaps,Tars, Kaspars,Maurops, Gundars,Ivdra, Natalija,Otikovs, Martins,Leitans, Janis,Kanepe-Lapsa, Iveta,Domraceva, Ilona,Mutule, Ilze,Trapencieris, Peteris,Blackman, Michael J.,Jirgensons, Aigars
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supporting information
p. 373 - 377
(2014/05/06)
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- Pd(ii)-Catalyzed arylation of unactivated methylene C(sp3)-H bonds with aryl halides using a removable auxiliary
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A Pd(ii)-catalyzed arylation of methylene C(sp3)-H bonds in aliphatic amides directed by our newly developed PIP directing group with aryl iodides/bromides has been achieved. Arylation occurs efficiently with a broad range of aryl halides and amides. This journal is the Partner Organisations 2014.
- Zhang, Qi,Yin, Xue-Song,Zhao, Sheng,Fang, Sheng-Long,Shi, Bing-Feng
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supporting information
p. 8353 - 8355
(2014/07/22)
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- Copper-mediated hydroxylation of arenes and heteroarenes directed by a removable bidentate auxiliary
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A copper-mediated C-H hydroxylation of arenes and heteroarenes using our newly developed PIP directing group has been developed. This procedure is scalable and compatible with a wide range of functional groups and heteroarenes, providing an operationally simple protocol for the synthesis of o-hydroxybenzamides. The hydroxylation of nicotinamides gave 4-oxo-1,4-dihydropyridine-3-carboxamides selectively. Preliminary mechanistic studies implicate that a basic ligand-enabled, irreversible, rate-determining CMD step is most likely involved in this process.
- Li, Xin,Liu, Yan-Hua,Gu, Wen-Jia,Li, Bo,Chen, Fa-Jie,Shi, Bing-Feng
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supporting information
p. 3904 - 3907
(2014/08/18)
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- Cu(II)-mediated C-S/N-S bond formation via C-H activation: Access to benzoisothiazolones using elemental sulfur
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A copper-mediated C-S/N-S bond-forming reaction via C-H activation that uses elemental sulfur has been developed. The addition of TBAI was found to be crucial for the success of this transformation. The method is scalable, shows excellent functional group tolerance, and is compatible with heterocycle substrates, providing efficient and practical access to benzoisothiazolones. The direct diversification of the benzoisothiazolone products into a variety of sulfur-containing compounds is also demonstrated.
- Chen, Fa-Jie,Liao, Gang,Li, Xin,Wu, Jun,Shi, Bing-Feng
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supporting information
p. 5644 - 5647
(2015/02/19)
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- Intramolecular redox-active ligand-to-substrate single-electron transfer: Radical reactivity with a palladium(II) complex
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Coordination of the redox-active tridentate NNO ligand LH2 to PdII yields the paramagnetic iminobenzosemiquinonato complex 3. Single-electron reduction of 3 yields diamagnetic amidophenolato complex 4, capable of activating aliphatic azide 5. Experimental and computational studies suggest a redox-noninnocent pathway wherein the redox-active ligand facilitates intramolecular ligand-to-substrate single-electron transfer to generate an open-shell singlet nitrene-substrate radical, ligand radical , enabling subsequent radical-type C-H amination reactivity with PdII.
- Broere, Dani?l L. J.,De Bruin, Bas,Reek, Joost N. H.,Lutz, Martin,Dechert, Sebastian,Van Der Vlugt, Jarl Ivar
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supporting information
p. 11574 - 11577
(2014/11/07)
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- Stereoselective synthesis of chiral α-amino-β-lactams through palladium(II)-catalyzed sequential monoarylation/amidation of C(sp 3)-H Bonds
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Give Me an Ar, give Me an N! Arylation of the methyl group in a simple derivative of readily available alanine under palladium catalysis was followed by intramolecular amidation at the same position to give chiral α-amino-β-lactams with a wide range of aryl substituents (see scheme; Phth=phthaloyl). The α-amino-β-lactams were obtained in moderate to high yields with good functional-group tolerance and high diastereoselectivity. Copyright
- Zhang, Qi,Chen, Kai,Rao, Weihao,Zhang, Yuejun,Chen, Fa-Jie,Shi, Bing-Feng
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supporting information
p. 13588 - 13592
(2014/01/06)
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- 1,5-DIPHENYL-PYRROLIDIN-2-ONE COMPOUNDS AS CB-1 LIGANDS
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CB-1 receptor inverse agonist compounds of Formula and pharmaceutical compositions for the treatment of obesity or cognitive impairment associated with schizophrenia.
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(2009/12/05)
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- COMPOUNDS FOR TREATING VIRAL INFECTIONS
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The invention relates to compounds, pharmaceutical compositions and methods useful for treating viral infection.
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Page/Page column 80; 87
(2008/12/08)
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- A PYRAZOLO[1,5-A]PYRIMIDINE COMPOUND
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The present invention provides a pyrazolo[1,5-a]pyrimidine compound, having CB1 receptor-antagonizing activity, of the following formula [I]: in which R1 and R2 are the same or different and each an optionally substituted aryl group etc, R0 is hydrogen atom, an alkyl group etc, E is a group of the formula: -C(=O)- or -SO?2#191-, R is a group of the following formula [i], [ii] or [iii] etc: Ring A is (a) a C?3-8#191 cycloalkyl group optionally fused to a benzene ring or (b) a benzene ring, Q is a single bond or a methylene group, Ring B is a 4- to 7-membered aliphatic heterocyclic group, said cyclic group binding via its ring-carbon atom to the adjacent nitrogen atom, X is sulfur atom etc, R3 is an alkyl group optionally substituted by an alkylthio group, R4 is hydrogen atom, an alkyl group etc, one of RA and RB is an alkyl group etc, and the other is hydrogen atom, an alkyl group etc, or a pharmaceutically acceptable salt thereof.
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Page/Page column 129-130
(2008/06/13)
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- Acridone-based inhibitors of inosine 5′-monophosphate dehydrogenase: Discovery and SAR leading to the identification of N-(2-(6-(4-ethylpiperazin-1- yl)pyridin-3-yl)propan-2-yl)-2-fluoro-9-oxo-9,10-dihydroacridine-3-carboxamide (BMS-566419)
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Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosine nucleotides, catalyzes the irreversible nicotinamide-adenine dinucleotide dependent oxidation of inosine-5′- monophosphate to xanthosine-5′-monophosphate. Mycophenolate Mofetil (MMF), a prodrug of mycophenolic acid, has clinical utility for the treatment of transplant rejection based on its inhibition of IMPDH. The overall clinical benefit of MMF is limited by what is generally believed to be compound-based, dose-limiting gastrointestinal (GI) toxicity that is related to its specific pharmacokinetic characteristics. Thus, development of an IMPDH inhibitor with a novel structure and a different pharmacokinetic profile may reduce the likelihood of GI toxicity and allow for increased efficacy. This article will detail the discovery and SAR leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability when administered orally in a rat adjuvant arthritis model.
- Watterson, Scott H.,Chen, Ping,Zhao, Yufen,Gu, Henry H.,Dhar, T. G. Murali,Xiao, Zili,Ballentine, Shelley K.,Shen, Zhongqi,Fleener, Catherine A.,Rouleau, Katherine A.,Obermeier, Mary,Yang, Zheng,McIntyre, Kim W.,Shuster, David J.,Witmer, Mark,Dambach, Donna,Chao, Sam,Mathur, Arvind,Chen, Bang-Chi,Barrish, Joel C.,Robl, Jeffrey A.,Townsend, Robert,Iwanowicz, Edwin J.
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p. 3730 - 3742
(2008/02/12)
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- CYANOFLUOROPYRROLIDINE DERIVATIVE
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A cyanofluoropyrrolidine compound of Formula (I) or a pharmaceutically acceptable salt thereof or a hydrate thereof, which is useful as an agent for preventing or treating diseases or conditions capable of being improved by inhibition of dipeptidyl peptidase IV (DPPIV), diabetes mellitus, immune diseases and the like: [wherein A represents a hydrogen atom or a fluorine atom, R1 and R2 are as defined in the specification, X represents a single bond or a C1-3 alkylene group, and R3 represents a group represented by the formula: -N(R4)COR5, -N(R4)SO2R5, -NR4R6, -SO2R5, -SO2NR4R5, -OCONR4R5, -CH=CH-R7 or -C≡C-R7, or represents a heteroaryl group selected from a heteroaryl group which contains at least one oxygen and/or sulfur atom and which may further contain a nitrogen atom, and a 6-membered nitrogen-containing aromatic ring or a 9- to 11-membered condensed ring thereof (wherein the heteroaryl group may be substituted with one or more substituents selected from the substituent Y3 group)].
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Page/Page column 29
(2010/11/08)
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- SUBSTITUTED PYRIDONES AS INHIBITORS OF POLY(ADP-RIBOSE) POLYMERASE (PARP)
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The present invention discloses and claims a series of 2,3,5-substituted pyridone derivatives as defined herein. This invention also relates to methods of making these compounds. The compounds of this invention are inhibitors of poly(adenosine 5'-diphosphate ribose) polymerase (PARP) and are therefore useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases, including diseases associated with the central nervous system and cardiovascular disorders.
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Page/Page column 147-148
(2010/02/14)
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