- Copper-Catalyzed Enantioconvergent Cross-Coupling of Racemic Alkyl Bromides with Azole C(sp2)?H Bonds
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The development of enantioconvergent cross-coupling of racemic alkyl halides directly with heteroarene C(sp2)?H bonds has been impeded by the use of a base at elevated temperature that leads to racemization. We herein report a copper(I)/cinchona-alkaloid-derived N,N,P-ligand catalytic system that enables oxidative addition with racemic alkyl bromides under mild conditions. Thus, coupling with azole C(sp2)?H bonds has been achieved in high enantioselectivity, affording a number of potentially useful α-chiral alkylated azoles, such as 1,3,4-oxadiazoles, oxazoles, and benzo[d]oxazoles as well as 1,3,4-triazoles, for drug discovery. Mechanistic experiments indicated facile deprotonation of an azole C(sp2)?H bond and the involvement of alkyl radical species under the reaction conditions.
- Chang, Xiao-Yong,Chen, Ji-Jun,Gu, Qiang-Shuai,Jiang, Sheng-Peng,Li, Zhong-Liang,Liu, Lin,Liu, Xiao-Dong,Liu, Xin-Yuan,Su, Xiao-Long,Wang, Fu-Li,Yang, Chang-Jiang,Ye, Liu
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p. 380 - 384
(2020/10/30)
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- 1H-INDAZOLE CARBOXAMIDES AS RECEPTOR-INTERACTING PROTEIN KINASE 1 INHIBITORS (RIPK1)
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Compounds having formula (I), and enantiomers, and diastereomers, stereoisomers, pharmaceutically-acceptable salts thereof, (I) are useful as kinase modulators, including RIPK1 modulation. All the variables are as defined herein.
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Page/Page column 69; 70
(2020/05/06)
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- Boron tribromide as a reagent for anti-Markovnikov addition of HBr to cyclopropanes
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Although radical formation from a trialkylborane is well documented, the analogous reaction mode is unknown for trihaloboranes. We have discovered the generation of bromine radicals from boron tribromide and simple proton sources, such as water ortert-butanol, under open-flask conditions. Cyclopropanes bearing a variety of substituents were hydro- and deuterio-brominated to furnish anti-Markovnikov products in a highly regioselective fashion. NMR mechanistic studies and DFT calculations point to a radical pathway instead of the conventional ionic mechanism expected for BBr3
- Chen, Shuming,Gieuw, Matthew H.,Houk, K. N.,Ke, Zhihai,Yeung, Ying-Yeung
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p. 9426 - 9433
(2020/10/02)
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- Method for synthesizing alkyne through catalytic asymmetric cross coupling (by machine translation)
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The invention belongs to the field of, asymmetric synthesis, and discloses a method for catalyzing asymmetric cross- coupling to synthesize: an alkyne, and the L method comprises, the following steps, of A: preparing B a cuprous, salt and C a: ligand; preparing a catalyst; adding a base; reacting the compound with the compound with the compound; and reacting the compound with the compound. Of these, one of them, X is selected from the group consisting of, R halogens. 1 Optionally substituted heteroarylsulfonylcyanamide groups selected from the, group consisting, of optionally substituted, phenyl groups In-flight vehicle, R6 Trialkyl silyl groups or alkyl radicals, R2 Cycloalkyl radicals optionally substituted with an, optionally substituted alkyl, (CH radical2 )n R4 Multi,layer chain, n=0-10,R saw blade4 A group selected, from, the group consisting of phenyl, alkenyl, aralkynyls, noonyloxy,and, noonylsulfonylsulfonylsulfonylsulfonylsulfonylsulfonylsulfonylsulfonylsulfonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylsulphonylphenyl disiloxy-radicals. R3 A ligand, selected from hydrogen or any of the functional groups, is selected from the group consisting of, hydrogen and any L other functional group. The method, R disclosed by the, A invention has the, advantages of good catalytic, R ’ effect, wide application range. and high catalytic efficiency, and the, method disclosed by the, invention has the. advantages of good catalytic effect, wide application range and high catalytic efficiency. (by machine translation)
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- SMALL MOLECULE INHIBITORS OF ALDH AND USES THEREOF
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This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a thiopyrimidinone structure which function as inhibitors of ALDH protein, and their use as therapeutics for the treatment of cancer and other diseases.
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Page/Page column 94-95
(2018/04/12)
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- HBr–DMPU: The First Aprotic Organic Solution of Hydrogen Bromide
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HBr and DMPU (1,3-dimethyl-3,4,5,6-tetrahydro-2-pyrimidinone) form a room-temperature-stable complex that provides a mild, effective, and selective hydrobrominating reagent toward alkynes, alkenes, and allenes. HBr–DMPU could also replace other halogenating reagents in the halo-Prins reaction, ether cleavage, and deoxy-bromination reactions.
- Li, Zhou,Ebule, Rene,Kostyo, Jessica,Hammond, Gerald B.,Xu, Bo
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supporting information
p. 12739 - 12743
(2017/09/25)
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- Silver-Catalyzed Decarboxylative Bromination of Aliphatic Carboxylic Acids
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The silver-catalyzed Hunsdiecker bromination of aliphatic carboxylic acids is described. With Ag(Phen)2OTf as the catalyst and dibromoisocyanuric acid as the brominating agent, various aliphatic carboxylic acids underwent decarboxylative bromination to provide the corresponding alkyl bromides under mild conditions. This method not only is efficient and general but also enjoys wide functional group compatibility. An oxidative radical mechanism involving Ag(II) intermediates is proposed.
- Tan, Xinqiang,Song, Tao,Wang, Zhentao,Chen, He,Cui, Lei,Li, Chaozhong
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supporting information
p. 1634 - 1637
(2017/04/11)
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- Transition-Metal-Free Stereospecific Cross-Coupling with Alkenylboronic Acids as Nucleophiles
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We herein report a transition-metal-free cross-coupling between secondary alkyl halides/mesylates and aryl/alkenylboronic acid, providing expedited access to a series of nonchiral/chiral coupling products in moderate to good yields. Stereospecific SN2-type coupling is developed for the first time with alkenylboronic acids as pure nucleophiles, offering an attractive alternative to the stereospecific transition-metal-catalyzed C(sp2)-C(sp3) cross-coupling.
- Li, Chengxi,Zhang, Yuanyuan,Sun, Qi,Gu, Tongnian,Peng, Henian,Tang, Wenjun
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supporting information
p. 10774 - 10777
(2016/09/09)
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- Visible-light-mediated benzylic sp3 C-H bond functionalization to C-Br or C-N bond
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A visible-light-promoted functionalization of unactivated benzylic sp3 C-H bonds was developed. Ethylbenzene derivatives were converted to the corresponding benzyl bromides or afforded benzylamine derivatives in a one-pot manner under visible light photoredox conditions.
- Hou, Tianyuan,Lu, Ping,Li, Pixu
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supporting information
p. 2273 - 2276
(2016/05/10)
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- Tribromoisocyanuric acid as a green reagent for benzylic bromination of alkylarenes
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The reaction of diverse alkylarenes with tribromoisocyanuric acid (0.34 mol equiv) in reflux EtOAc in the absence of any catalysts or light irradiation produced the corresponding benzyl bromides in 53-88% yield.
- De Almeida, Leonardo S.,Esteves, Pierre M.,De Mattos, Marcio C.S.
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p. 6843 - 6845
(2015/11/27)
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- N-alkylation of lactams with secondary heterobenzylic bromides
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We herein report a general N-alkylation reaction of lactams with secondary heterobenzylic bromides. This methodology features mild reaction condition, moderate to high product isolation yield, and broad substrate scope. Good chemical and structural tolerance has also been demonstrated by both the secondary heterobenzylic bromides and lactam substrates.
- Yu, Ming,Stevenson, Karis,Zhou, Gene
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supporting information
p. 5591 - 5594
(2014/12/11)
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- Catalytic enantioselective cross-couplings of secondary alkyl electrophiles with secondary alkylmetal nucleophiles: Negishi reactions of racemic benzylic bromides with achiral alkylzinc reagents
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We have developed a nickel-catalyzed method for the asymmetric cross-coupling of secondary electrophiles with secondary nucleophiles, specifically, stereoconvergent Negishi reactions of racemic benzylic bromides with achiral cycloalkylzinc reagents. In contrast to most previous studies of enantioselective Negishi cross-couplings, tridentate pybox ligands are ineffective in this process; however, a new, readily available bidentate isoquinoline-oxazoline ligand furnishes excellent ee's and good yields. The use of acyclic alkylzinc reagents as coupling partners led to the discovery of a highly unusual isomerization that generates a significant quantity of a branched cross-coupling product from an unbranched nucleophile.
- Binder, Joerg T.,Cordier, Christopher J.,Fu, Gregory C.
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supporting information
p. 17003 - 17006,4
(2012/12/11)
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- Catalytic enantioselective cross-couplings of secondary alkyl electrophiles with secondary alkylmetal nucleophiles: Negishi reactions of racemic benzylic bromides with achiral alkylzinc reagents
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We have developed a nickel-catalyzed method for the asymmetric cross-coupling of secondary electrophiles with secondary nucleophiles, specifically, stereoconvergent Negishi reactions of racemic benzylic bromides with achiral cycloalkylzinc reagents. In contrast to most previous studies of enantioselective Negishi cross-couplings, tridentate pybox ligands are ineffective in this process; however, a new, readily available bidentate isoquinoline-oxazoline ligand furnishes excellent ee's and good yields. The use of acyclic alkylzinc reagents as coupling partners led to the discovery of a highly unusual isomerization that generates a significant quantity of a branched cross-coupling product from an unbranched nucleophile.
- Binder, Joerg T.,Cordier, Christopher J.,Fu, Gregory C.
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supporting information
p. 17003 - 17006
(2013/01/15)
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- Theoretical and experimental studies on stability of the C-ON bond in new ketone functionalized N-alkoxyamines
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Three new ketone functionalized N-alkoxyamines derived from 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO) were prepared: N-(1-phenylpropyloxy) -2,2,6,6-tetramethylpiperidin-4-one, 1-phenyl-1-(2,2,6,6- tetramethylpiperidinoxy)propanone, 1-phenyl-1-(4-oxo-2,2,6,6- tetramethylpiperidinoxy)propanone. The rate constants of C-ON bonds homolysis in the synthesized alkoxyamines were determined over a range of temperatures via nitroxide-exchange experiments using HPLC to monitor the concentration. The Arrhenius parameters of homolysis for the investigated alkoxyamines were determined (lnA, Ea). Homolytic bond dissociation energies (BDE) of the C-ON bond in the synthesized compounds were determined from quantum-mechanical calculations at the B3-LYP/6-31G(d) and BMK/6-311+G(3df,2p) levels. Ketone functionalization of the alkyl fragment of alkoxyamine in β position dramatically increases the rate constant of homolysis (by a factor of ca. 500 at the temperature of 363 K) suggesting that the new ketone functionalized N-alkoxyamines should be effective as C-radical precursor and unimolecular initiators in NMRP at lower temperatures than the alkoxyamines applied earlier. The analyses of natural bond, frontal orbitals and spin distribution indicated that the decrease in the strength of C-ON bonds in ketone fuctionalized alkoxyamines in the alkyl fragment predominantly originates from a substantially smaller HOMO-LUMO gap and more delocalized spin density in leaving alkyl radicals as compared with unfunctionalized alkoxyamines. Copyright
- Megiel, Elzbieta,Kaim, Andrzej,Cyranski, Michal Ksawery
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experimental part
p. 1146 - 1154
(2011/09/20)
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- A new diphenylphosphinite ionic liquid (IL-OPPh2) as reagent and solvent for highly selective bromination, thiocyanation or isothiocyanation of alcohols and trimethylsilyl and tetrahydropyranyl ethers
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A new diphenylphosphinite ionic liquid (IL-OPPh2) is introduced. This ionic liquid is used as both a reagent and a solvent to convert alcohols and trimethylsilyl and tetrahydropyranyl (THP) ethers into their corresponding alkyl bromides, thiocyanates or isothiocyanates in the presence of Br2 and SCN- at 80 °C. In this ionic liquid, bromination and thiocyanation of alcohols occurs highly selectively in the presence of trimethylsilyl and THP-ethers and also between different classes of alcohols. The use of this ionic liquid allows easy separation of the desired products from the phosphinate by-product.
- Iranpoor, Nasser,Firouzabadi, Habib,Azadi, Roya
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p. 5531 - 5534
(2007/10/03)
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- Wittig-Horner approach for the synthesis of tamoxifen
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A stereoselective synthesis of Z-tamoxifen, a tetra-substituted alkene with antiestrogenic activity, is described. The Wittig-Horner reaction has been employed as the key step to establish the olefin stereochemistry. Copyright Taylor & Francis, Inc.
- Pandey, Rajesh K.,Wakharkar,Kumar, Pradeep
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p. 2795 - 2800
(2007/10/03)
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- Substrate activation: Indirect β-bromination of alcohols
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The reversible oxidation of an alcohol into a ketone provides access to enol/enolate chemistry. Preliminary results have applied this principle to the β-bromination of alcohols.
- Cami-Kobeci, Gerta,Williams, Jonathan M.J.
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p. 124 - 126
(2007/10/03)
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- A simple and efficient iodination of alcohols on polymer-supported triphenylphosphine
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A simple, mild, and high-yielding procedure for the iodination of allylic, benzylic, and other primary alcohols using a combination of iodine and imidazole on polymer-supported triphenyl phosphine is described.
- Anilkumar, Gopinathan,Nambu, Hisanori,Kita, Yasuyuki
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p. 190 - 191
(2013/09/06)
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- Asymmetric synthesis of alpha,beta-dialkyl-alpha-phenylalanines via direct alkylation of a chiral alanine derivative with racemic alpha-alkylbenzyl bromides. A case of high enantiomer differentiation at room temperature.
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[figure: see text] This study demonstrates that the direct alkylation of a Ni(II)-complex of the chiral Schiff base of alanine with (S)-o-[N-(N-benzylprolyl)amino]- benzophenone, with racemic alpha-alkylbenzyl bromides, is a synthetically feasible and methodologically advantageous approach to the target alpha,beta-dialkylphenylalanines over previously reported methods. For the first time we report and rationalize a case of a high enantiomer differentiation process at room temperature.
- Soloshonok,Tang,Hruby,Van Meervelt
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p. 341 - 343
(2007/10/03)
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- Concave reagents, 30. Diastereoselective generation of quaternary stereocenters by ligand-controlled palladium-catalyzed allylations
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The 1,2-asymmetric induction in the formation of new quaternary centers by palladium-catalyzed allylation of substituted cyanoacetates 1a-c was controlled by using 2,9-disubstituted 1,10-phenanthrolines as ligands, giving the allylated products 3a-c with
- Meynhardt,Lüning,Wolff,N?ther
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p. 2327 - 2335
(2007/10/03)
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- Stereocontrol in the intramolecular Buchner reaction of diazoketones
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Rhodium(II) acetate catalysed intramolecular Buchner cyclisation of a series of diazoketones 1 proceeds with excellent diastereoselectivity to produce the trans substituted azulenones 2, which exist as a rapidly equilibrating cycloheptatriene-norcaradiene system, from which the norcaradiene tautomers can be efficiently trapped as PTAD cycloadducts 4. The cyclisation-cycloaddition sequence can be conducted in either a stepwise or a tandem process, leading to the pentacyclic systems 4 as a single diastereomer in each case. In the reaction of diazoketone If intramolecular cyclopropanation competes with cyclisation to the aromatic ring.
- Maguire, Anita R.,Buckley, N. Rachael,O'Leary, Patrick,Ferguson, George
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p. 4077 - 4091
(2007/10/03)
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- Synthesis of 3-Phenoxybenzyl 3-Alkyl-3-phenyl-/p-substituted phenyl and 3-Phenoxybenzyl 2-Alkyl-3-phenyl-/p-substituted phenylpropionates
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Some 3-phenoxybenzyl 3-alkyl-3-phenyl-/p-substituted phenylpropionates (VII, XI, XV, XIX, XXIII, XXVII) which resemble structurally the 1,2-secopyrethroids, have been prepared employing simple reactions like alkylation, decarbethoxylation and transesterification.The synthesis of 3-phenoxybenzyl 2-alkyl-3-phenyl-/p-substituted phenyl-propionates (XXXI, XXXII, XXXIII, and XXXVI) bearing close structural resemblance to 2,3-secopyrethroids has also been described.
- Kelkar, S. V.,Joshi, G. S.,Kulkarni, G. H.,Mitra, R. B.
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- DIASTEREOSELECTION IN RHODIUM-MEDIATED INTRAMOLECULAR C-H INSERTION: PREPARATION OF A TRANS-3,4 DIALKYL CYCLOPENTANE
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Transition state analysis suggests that substantial 1,2 asymmetric induction could be observed in the course of rhodium-mediated intramolecular C-H insertion.This analysis succesfully predicts predominant formation of the trans 3,4-dialkyl cyclopentane wh
- Taber, Douglass F.,Ruckle, Robert E.
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p. 3059 - 3062
(2007/10/02)
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- Synthesis and receptor-binding affinity of fluorotamoxifen, a possible estrogen-receptor imaging agent
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Aminotamoxifen was totally synthesized from p-nitrobenzoyl chloride via a Friedel-Crafts acylation. Then, by means of a Balz-Schiemann reaction, aminotamoxifen was converted into fluorotamoxifen. The triazene variation of this conversion, with a 25% yield, enables a rapid, one-step diazotization, incorporating a fluorine atom into the phenyl ring of the tamoxifen. This reaction may be useful for the preparation of low specific activity 18F-labeled tamoxifen, for distribution, and for estrogen-receptor studies. For these in vivo and in vitro studies, fluorotamoxifen was also synthesized from p-fluorobenzoyl chloride, and its chemical intermediates were compared with estradiol and hexestrol, for their receptor binding and competition, as well as for their uterotropic activity. It is demonstrated that tamoxifen and fluorotamoxifen are strong estradiol agonists and partial hexestrol agonists, while aminotamoxifen is a weak estradiol and hexestrol agonist.
- Shani,Gazit,Livshitz,Biran
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p. 1504 - 1511
(2007/10/02)
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