- Br?nsted acid-catalyzed enantioselective addition of 1,3-diones to in situ generated N-acyl ketimines
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A Br?nsted acid-catalyzed asymmetric Mannich-type addition of 1,3-diones to cyclic N-acyl ketimines is reported for the synthesis of enantioenriched isoindolinones. Various dicarbonyl-substituted isoindolinones bearing a quaternary carbon stereocenter were synthesized with excellent yields (up to 98%) and moderate to high enantioselectivities (up to 95% ee), and most of them possess a fluorine atom at the reactive center. Furthermore, the synthetic utility of the protocol has been demonstrated by the debenzoylation of the product.
- Sadhu, Milon M.,Ray, Sumit K.,Unhale, Rajshekhar A.,Singh, Vinod K.
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supporting information
p. 410 - 414
(2022/01/20)
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- A Serendipitous One-Pot Cyanation/Hydrolysis/Enamide Formation: Direct Access to 3-Methyleneisoindolin-1-ones
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A direct, one-pot conversion of 2’-haloacetophenones to 3-methyleneisoindolin-1-one scaffolds using CuCN as the sole reagent without the need for moisture-free or anaerobic conditions is reported. This serendipitously discovered transformation with a broa
- Banik, Trisha,Kaliappan, Krishna P.
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supporting information
p. 628 - 633
(2020/12/09)
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- Testing the limits of radical-anionic CH-amination: A 10-million-fold decrease in basicity opens a new path to hydroxyisoindolines via a mixed C-N/C-O-forming cascade
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An intramolecular C(sp3)-H amidation proceeds in the presence of t-BuOK, molecular oxygen, and DMF. This transformation is initiated by the deprotonation of an acidic N-H bond and selective radical activation of a benzylic C-H bond towards hydrogen atom transfer (HAT). Cyclization of this radical-anion intermediate en route to a two-centered/three-electron (2c,3e) C-N bond removes electron density from nitrogen. As this electronegative element resists such an oxidation , making nitrogen more electron rich is key to overcoming this problem. This work dramatically expands the range of N-anions that can participate in this process by using amides instead of anilines. The resulting 107-fold decrease in the N-component basicity (and nucleophilicity) doubles the activation barrier for C-N bond formation and makes this process nearly thermoneutral. Remarkably, this reaction also converts a weak reductant into a much stronger reductant. Such reductant upconversion allows mild oxidants like molecular oxygen to complete the first part of the cascade. In contrast, the second stage of NH/CH activation forms a highly stabilized radical-anion intermediate incapable of undergoing electron transfer to oxygen. Because the oxidation is unfavored, an alternative reaction path opens via coupling between the radical anion intermediate and either superoxide or hydroperoxide radical. The hydroperoxide intermediate transforms into the final hydroxyisoindoline products under basic conditions. The use of TEMPO as an additive was found to activate less reactive amides. The combination of experimental and computational data outlines a conceptually new mechanism for conversion of unprotected amides into hydroxyisoindolines proceeding as a sequence of C-H amidation and C-H oxidation.
- Alabugin, Igor V.,Dos Passos Gomes, Gabriel,Elliott, Quintin,Evoniuk, Christopher J.
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p. 6539 - 6555
(2020/07/15)
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- COMPOUND HAVING BET INHIBITORY ACTIVITY AND PREPARATION METHOD AND USE THEREFOR
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The invention relates to the field of pharmaceutical chemistry. Specifically, the present invention relates to a series of BET (bromodomain and extra-terminal domain) inhibitors having a novel structure, particularly inhibitors targeting BRD4 (Bromodomain-containing protein 4), and a preparation method and use therefor. The structure thereof is shown in the following general formula (I). Said compounds or a stereoisomer, racemate, geometric isomer, tautomer, prodrug, hydrate, solvate, or crystal form thereof, or a pharmaceutically acceptable salt thereof, and the pharmaceutical compsosition thereof can be used for the treatment and/or prevention of related diseases mediated by bromodomain proteins.
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Paragraph 0198-0199
(2020/12/22)
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- BF3·OEt2-Catalyzed Vinyl Azide Addition to in Situ Generated N-Acyl Iminium Salts: Synthesis of 3-Oxoisoindoline-1-acetamides
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BF3·OEt2-catalyzed nucleophilic addition of vinyl azides to in situ generated N-acyl iminium salts obtained from 3-hydroxyisoindolinones is described in this article. The procedure is operationally simple, mild, additive, and metal-free. The reaction proceeds smoothly at ambient temperature with a wide range of 3-hydroxyisoindol-1-ones and vinyl azides to afford 3-oxoisoindoline-1-acetamides (32 examples) in high yields (up to 97%). Furthermore, the synthetic utility of this methodology is depicted by exploiting the reactivity of an amide functionality in the products.
- Kumar Das, Deb,Kannaujiya, Vinod Kumar,Sadhu, Milon M.,Ray, Sumit Kumar,Singh, Vinod K.
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p. 15865 - 15876
(2019/12/24)
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- o-Acylbenzonitriles: Synthesis and Heterocyclization under Acid Hydrolysis of the Cyano Group
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2-Cyanobenzophenones were synthesized by reaction of 2-bromobenzophenones with copper(I) cyanide in DMF, and their transformations involving acid hydrolysis of the cyano group were studied. Reactions of o-benzoylbenzonitriles with trifluoroacetic acid in
- Mochalov,Fedotov,Trofimova,Zefirov
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p. 403 - 413
(2018/06/12)
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- Novel spiroisoindolinone derivatives, preparation method thereof and pharmaceutical compositions for the prevention and treatment of cancer containing the same as an active ingredient
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The present invention relates to a novel spiro isoindolinone derivative having an anticancer activity, a preparation method thereof, and a pharmaceutical composition comprising the same as an active ingredient and, more specifically, to a spiro isoindolinone derivative produced as a result of [3+2] ring formation using a Rhodium (III) catalyst, a preparation method thereof, and a composition for preventing or treating cancer comprising the same as an active ingredient. A novel spiro isoindolinone derivative according to the present invention shows an excellent anticancer activity against various human cancer cell lines, and thus is expected to be useful as a pharmaceutical composition for preventing and treating cancer. In addition, a method for preparing a spiro isoindolinone derivative using a Rhodium (III) catalyst of the present invention can be applied and introduced to a wide range of functional groups, and is very useful in synthesizing a novel medicine or a compound having a biological activity as a reaction having position selectivity and chemical selectivity.COPYRIGHT KIPO 2018
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Paragraph 0134; 0138
(2018/08/02)
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- Enantioselective Trapping of Oxonium Ylides by 3-Hydroxyisoindolinones via a Formal SN1 Pathway for Construction of Contiguous Quaternary Stereocenters
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An enantioselective Rh(II)/chiral phosphoric acid co-catalyzed three-component reaction via trapping of oxonium ylides with 3-hydroxyisoindolinones by a formal SN1 pathway is described. This reaction allows for the efficient synthesis of isoindolinone derivatives with two contiguous quaternary stereogenic centers in high yields (up to 93%) with excellent enantioselectivities and moderate diastereoselectivities under mild reaction conditions.
- Kang, Zhenghui,Zhang, Dan,Shou, Jiayi,Hu, Wenhao
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supporting information
p. 983 - 986
(2018/02/23)
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- Asymmetric hydrogenolysis of racemic 3-substitued-3-hydroxy-isoindolin-1-ones employing SPINOL-derived chiral phosphoric acid
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The asymmetric hydrogenolysis of racemic 3-substitued-3-hydroxyisoindolin-1-ones has been developed employing SPINOL-derived phosphoric acid and a high steric demand Hantzsch ester as the hydrogen source. The corresponding products are obtained in good yields and up to 93% enantioselectivities.
- Zhang, Yiliang,He, Li,Shi, Lei
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supporting information
p. 1592 - 1595
(2018/03/26)
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- A chiral Br?nsted acid-catalyzed highly enantioselective Mannich-type reaction of α-diazo esters with in situ generated N -acyl ketimines
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A chiral phosphoric acid-catalyzed asymmetric Mannich-type reaction of α-diazo esters with in situ generated N-acyl ketimines, derived from 3-hydroxyisoindolinones has been demonstrated in this communication. A variety of isoindolinone-based α-amino diazo esters bearing a quaternary stereogenic center were afforded in high yields (up to 99%) with excellent enantioselectivities (up to 99% ee). Furthermore, the synthetic utility of the products has been depicted by the hydrogenation of the diazo moiety of adducts.
- Unhale, Rajshekhar A.,Sadhu, Milon M.,Ray, Sumit K.,Biswas, Rayhan G.,Singh, Vinod K.
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supporting information
p. 3516 - 3519
(2018/04/10)
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- Rhodium-Catalyzed [3 + 2] Annulation of Cyclic N-Acyl Ketimines with Activated Olefins: Anticancer Activity of Spiroisoindolinones
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The rhodium(III)-catalyzed redox-neutral coupling reaction of N-acyl ketimines generated in situ from 3-hydroxyisoindolinones with various activated olefins is described. This approach leads to the synthesis of bioactive spiroisoindolinone derivatives in
- Sharma, Satyasheel,Oh, Yongguk,Mishra, Neeraj Kumar,De, Umasankar,Jo, Hyeim,Sachan, Richa,Kim, Hyung Sik,Jung, Young Hoon,Kim, In Su
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p. 3359 - 3367
(2017/04/13)
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- Ir(I)-catalyzed enantioselective hydrogenolysis of 3-aryl-3-hydroxyisoindolin-1-ones
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An enantioselective hydrogenolysis of 3-aryl-3-hydroxyisoindolin-1-ones under H2has been developed by using Ir(I)/(R)-MeO-Biphep complex as a catalyst. Cyclic diaryl methylamides were obtained in moderate to excellent yields and up to 92%?ee.
- Ge, Chen,Liang, Ren-Xiao,Liu, Ren-Rong,Xiang, Bin,Jia, Yi-Xia
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supporting information
p. 142 - 144
(2016/12/23)
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- Enantioselective Hydrophosphonylation of in Situ Generated N-Acyl Ketimines Catalyzed by BINOL-Derived Phosphoric Acid
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An efficient route to pharmacologically interesting isoindolinone-based α-amino phosphonates is described via asymmetric hydrophosphonylation of in situ generated ketimines catalyzed by BINOL-derived phosphoric acid. The reaction proceeds smoothly at ambient temperature affording a variety of α-amino phosphonates with a quaternary stereogenic center embedded in isoindolinone motif in high yields with excellent enantiomeric ratios (up to 98.5:1.5 er). Several interesting transformations of the products into valuable synthetic intermediates are also depicted.
- Suneja, Arun,Unhale, Rajshekhar A.,Singh, Vinod K.
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supporting information
p. 476 - 479
(2017/02/10)
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- Chiral Br?nsted acid-catalysed enantioselective synthesis of isoindolinone-derived N(acyl),S-acetals
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The first organocatalytic asymmetric addition of thiols to N-acyl ketimines, which are generated in situ from 3-hydroxy isoindolinones, is described. The reaction proceeds smoothly with a broad range of ketimines and thiols using a chiral Br?nsted acid catalyst to afford N(acyl),S-acetals comprising a tetrasubstituted stereocenter in high yields and enantioselectivities (up to 98.5:1.5 e.r.). The usefulness of the developed protocol is demonstrated in the synthesis of a known HIV-1 reverse transcriptase inhibitor.
- Su?, Josipa,Dokli, Irena,Gredi?ak, Matija
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supporting information
p. 2071 - 2074
(2016/02/09)
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- Catalytic [3 + 2] annulation of ketimines with alkynes via C-H activation by a cationic iridium(cod) complex
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[3 + 2] Annulation of ketimines with internal and terminal alkynes proceeded via C-H activation to give aminoindene derivatives in high yields, which is catalyzed by a cationic iridium complex coordinated with 1,5-cyclooctadiene (cod). This journal is the Partner Organisations 2014.
- Nagamoto, Midori,Nishimura, Takahiro
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supporting information
p. 6274 - 6277
(2014/06/09)
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- Hydroxorhodium/chiral diene complexes as effective catalysts for the asymmetric arylation of 3-aryl-3-hydroxyisoindolin-1-ones
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Water is out, aryl is in! Asymmetric synthesis of isoindoline-1-ones bearing an α-triaryl-substituted stereogenic center was realized in the enantioselective addition of arylboroxines to 3-aryl-3-hydroxyisoindolin-1-ones in the presence of a hydroxorhodium/chiral diene catalyst, where cyclic N-carbonyl ketimines were generated in situ by dehydration. Copyright
- Nishimura, Takahiro,Noishiki, Akira,Ebe, Yusuke,Hayashi, Tamio
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p. 1777 - 1780
(2013/04/10)
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- Chiral phosphoric acid catalyzed asymmetric hydrogenolysis of racemic 3-aryl-3-hydroxyisoindolin-1-ones
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The enantioselective hydrogenolysis of racemic 3-aryl-3-hydroxyisoindolin- 1-ones catalyzed by BINOL-derived chiral phosphoric acid with benzothiazoline as the hydride source is described. The corresponding cyclic diaryl methylamines are obtained in good to excellent yields and up to 91% enantioselectivities.
- Zhou, Jian-Qing,Sheng, Wei-Jian,Jia, Jian-Hong,Ye, Qing,Gao, Jian-Rong,Jia, Yi-Xia
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supporting information
p. 3082 - 3084
(2013/06/27)
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- Hydrogenolysis of the C-O bond of hydroxylactams as a convenient method for the synthesis of substituted isoindolin-1-ones
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A simple and efficient method for the synthesis of isoindolin-1-ones containing alkyl or aryl substituents at positions 2 and (or) 3 was suggested. The method is based on the earlier unknown Pd0-catalyzed hydrogenolysis of hydroxylactams.
- Sagirova,Starodubtseva,Turova,Vinogradov
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p. 1032 - 1037
(2014/03/21)
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- A Practical Two-Step Synthesis of 3-Alkyl-2,3-dihydro-1H-isoindolin-1-ones
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A flexible approach to 3-alkyl-2,3-dihydro-1H-isoindolin-1-ones via the reductive-alkylation procedure is described. Present method is versatile in scope, allowing the easy introduction of various C-3 carbon-substituents by Grignard addition to phthalimid
- Ruan, Yuan-Ping,Chen, Ming-De,He, Ming-Zhu,Zhou, Xiang,Huang, Pei-Qiang
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p. 853 - 861
(2007/10/03)
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- A new synthesis of 3-alkyl-1-isoindolinones
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A new, concise, and efficient method for the synthesis of 3-alkyl-1-isoindolinones was described. 3-Alkyl-3-hydroxy-2,3-dihydro-1-isoindolinones, prepared from the reaction of phthalimide and alkyl lithium, were treated with sodium cyanoborohydride in aci
- Wang, Eng-Chi,Chen, Hsien-Fan,Feng, Pei-Kuan,Lin, Yu-Li,Hsu, Ming-Kuan
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p. 9163 - 9165
(2007/10/03)
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- Heteroatom-Directed Metalation. Lithiation of N-Propenylbenzamides and N-Propenyl-o-toluamides. Novel Routes to Ortho-Substituted Primary Benzamide Derivatives and N-Unsubstituted Isoquinolin-1(2H)-ones
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Reaction of N-propenylbenzamides 4 and 9, obtained by LDA-induced isomerization of the corresponding N-allylbenzamides, 1, 8, and 14, with 2 equiv of sec-butyllithium or tert-butyllithium at low temperature regiospecifically generates the highly reactive N,ortho-dilithiated species (e.g., 5 and 17).These dilithio species react avidly with a wide spectrum of electophilic reagents, including alky halides, giving adducts which on hydrolysis with warm 50percent aqueous acetic acid are converted into ortho-substituted primary benzamides in excellent yields.Ortho-lithiation of N-propenylbenzamides is thus formally equivalent to ortho-lithiation of primary benzamides themselves.The utility of this important, previously unknown, synthetic operation is enhanced by the well-known facility with which the primary amide moiety can be transformed into other useful functional groups, as exemplified by the synthesis of 2-methoxy-6-methylbenzoic acid (12) and 2-methoxy-6-methylbenzonitrile (13) from N-propenyl-2-methoxybenzamide (9).N-Propenyl-o-toluamide (7) undergoes regiospecific dilithiation on nitrogen and on the methyl group under conditions analogous to those used for the N-propenylbenzamides.These dilithio species react with DMF or "Weinreb type" amides to give condensation products which cyclize to N-propenylisoquinolin-1(2H)-ones under mildly acidic conditions.Removal of the N-propenyl moiety under more strongly acidic conditions provides N-unsubstituted isoquinolin-1(2H)-ones with high overall efficiency.This process is exemplified by the synthesis of isoquinolin-1(2H)-one (23) and its 3-n-butyl congener 26 from N-propenyl-2-methylbenzamide (7).
- Fisher, Lawrence E.,Muchowski, Joseph M.,Clark, Robin D.
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p. 2700 - 2705
(2007/10/02)
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