- Metal-free approach for hindered amide-bond formation with hypervalent iodine(iii) reagents: application to hindered peptide synthesis
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A new bio-inspired approach is reported for amide and peptide synthesis using α-amino esters that possess a potential activating group (PAG) at the ester residue. To activate the ester functionality under mild metal-free conditions, we exploited the facile dearomatization of phenols with hypervalent iodine(iii) reagents. Using a pyridine-hydrogen fluoride complex, highly reactive acyl fluoride intermediates can be successfully generated, thereby allowing for the smooth formation of sterically hindered amides and peptides from bulky amines and α-amino esters, respectively.
- Lee, Hyo-Jun,Huang, Xiao,Sakaki, Shigeyoshi,Maruoka, Keiji
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supporting information
p. 848 - 855
(2021/02/09)
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- A Hydroperoxide-Mediated Decarboxylation of α-Ketoacids Enables the Chemoselective Acylation of Amines
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Strategies for the formation of amide bonds, that is, one of the most basic and important transformations in organic synthesis, have so far focused predominantly on dehydration reactions. Herein, we report and demonstrate the practical utility of a novel decarboxylative amidation of α-ketoacids by using inexpensive tert-butyl hydroperoxide (TBHP), which is characterized by high yields, a broad substrate scope, mild reaction conditions, and a unique chemoselectivity. These features enable the synthesis of peptides from amino acid derived α-ketoacids under preservation of the stereochemical information.
- Nanjo, Takeshi,Kato, Natsuki,Zhang, Xuan,Takemoto, Yoshiji
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supporting information
p. 15504 - 15507
(2019/11/14)
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- An Unconventional Reaction of 2,2-Diazido Acylacetates with Amines
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We have discovered that 2,2-diazido acylacetates, a class of compounds with essentially unknown reactivity, can be coupled to amines through a new strategy that does not involve any reagents. 2,2-Diazido acetate is the unconventional leaving group under carbon–carbon bond cleavage. This reaction leads to the construction of amide bonds, tolerates various functionalities and is performed equally well in numerous solvents under experimentally simple conditions. We also demonstrate that the isolation of the 2,2-diazido acylacetate compounds can be circumvented: Acylacetates were easily fragmented when treated with (Bu4N)N3 and iodine in the presence of an amine at room temperature. By using this method, a broad range of acylacetates with various structural motifs were directly transformed into amides.
- H?ring, Andreas P.,Biallas, Phillip,Kirsch, Stefan F.
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supporting information
p. 1526 - 1539
(2017/04/01)
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- Direct NHC-catalysed redox amidation using CO2 for traceless masking of amine nucleophiles
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The N-heterocyclic carbene (NHC)-catalysed redox amidation reaction is poorly developed and usually requires catalytic co-additives for electron-rich amine nucleophiles. We report a masking strategy (using CO2) that couples release of the free amine nucleophile to catalytic turnover, and in doing so, enables direct catalytic redox amidation of electron-rich amines.
- Davidson, Robert W. M.,Fuchter, Matthew J.
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supporting information
p. 11638 - 11641
(2016/10/04)
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- A two-step, one pot preparation of amines via acyl succinimides. Synthesis of the calcimimetic agents cinacalcet, NPS R-467, and NPS R-568
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Abstract A method has been developed for the preparation of amines through a process of coupling acyl succinimides derived from commercially available carboxylic acids with amines to afford the corresponding amides. These amides are then reduced in situ with either diisobutylaluminum hydride or lithium aluminum hydride. The reaction tandem of the coupling reaction followed by the reduction affords the amine in fair to good yields after purification by flash chromatography. This one-pot, two reaction tandem process has been successfully applied to the synthesis of the calcimimetic agents cinacalcet, NPS R-467, and NPS R-568.
- Gooodman, Cassie A.,Janci, Elise Marie,Onwodi, Olivia,Simpson, Chad C.,Hamaker, Christopher G.,Hitchcock, Shawn R.
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supporting information
p. 4468 - 4471
(2015/06/30)
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- FENDILINE DERIVATIVES AND METHODS OF USE THEREOF
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Disclosed herein are novel derivatives of fendiline, including compounds of the formula: wherein the variables are defined herein. Also provided are pharmaceutical compositions, kits and articles of manufacture comprising these derivative compounds. Methods and intermediates useful for making the derivatives, and methods of using the derivatives, for example, for the inhibition of K-Ras plasma membrane localization, and compositions thereof, including for the treatment of cancer, are also provided.
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Page/Page column 69; 70
(2014/03/25)
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- Pseudomonas stutzeri lipase: A useful biocatalyst for aminolysis reactions
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The use of Pseudomonas stutzeri lipase (PSL) as a biocatalyst for aminolysis reactions with bulky substrates has been investigated. PSL compared favorably to Novozym 435 (immobilized Candida antarctica lipase B, NOV435) in the aminolysis of various bulky methyl esters and amines. While NOV435 demonstrated a higher rate of aminolysis with methyl 2-phenylpropionic acid as the acyl donor, PSL outperformed NOV435 with secondary amines as the nucleophile. Methanol inhibition and a low affinity for bulky acyl donors were found to be the two main reasons for relatively low rates in the PSL-catalyzed aminolysis reactions. It was demonstrated that the use of molsieve 4A had a significant effect on the aminolysis rate and amide yield, since it enabled the effective removal of the inhibiting methanol from the reaction mixture.
- Van Pelt,Teeuwen,Janssen,Sheldon,Dunn,Howard,Kumar,Martinez,Wong
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experimental part
p. 1791 - 1798
(2011/10/09)
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- Highly efficient method for the synthesis of carboxamides from carboxylic acids and amines using pyridine-3-sulfonyl chloride (3-PSC)
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The use of pyridine-3-sulfonyl chloride (3-PSC) in dehydrating condensation was investigated. This novel reagent was successfully employed as a mild dehydrating reagent for preparing various carboxamides in good to excellent yields from the corresponding carboxylic acids and amines. Copyright
- Funasaka, Setsuo,Kato, Koji,Mukaiyama, Teruaki
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p. 506 - 507
(2008/09/21)
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- A versatile, practical, and inexpensive reagent, pyridine-3-carboxylic anhydride (3-PCA), for condensation reactions
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A highly useful method for the preparation of carboxylic esters and carboxamides from various carboxylic acids was established by using a novel condensing reagent, pyridine-3-carboxylic anhydride (3-PCA), in the presence of 4-(dimethylamino)pyridine as an activator. The reactions of various carboxylic acids with nucleophiles, such as alcohols or amines, afforded the corresponding carboxylic acids or carboxamides in good to high yields under mild conditions by using simple experimental procedure. In addition, it was confirmed that this protocol was applicable to a gram-scale synthesis and the by-products, including pyridine-3-carboxylic acid and pyridine-3-carboxylate (or pyridine-3- carboxamide) produced in situ, were easily removed by using a simple aqueous workup.
- Funasaka, Setsuo,Mukaiyama, Teruaki
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experimental part
p. 148 - 159
(2009/04/06)
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- Highly efficient method for the synthesis of carboxamides from carboxylic acids and amines using benzenesulfonic anhydride (BSA)
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A highly efficient method by using benzenesulfonic anhydride (BSA) in the presence of 4-(dimethylamino)pyridine (DMAP) to synthesize carboxamides from various carboxylic acids and amines including sterically hindered ones is established. This reaction proceeds smoothly to provide the desired product in high yield. Copyright
- Funasaka, Setsuo,Kato, Koji,Mukaiyama, Teruaki
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p. 1456 - 1457
(2008/03/14)
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- Efficient method for dehydration condensation using pyridine-3-carboxylic anhydride (3-PCA): Synthesis of carboxamides from nearly equimolar amounts of carboxylic acids and amines
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A highly useful method for the preparation of carboxamides from various carboxylic acids and amines is established by using pyridine-3-carboxylic anhydride (3-PCA) in the presence of 4-(dimethylamino)pyridine (DMAP). This reaction proceeds smoothly under mild conditions by simple experimental procedure. Copyright
- Funasaka, Setsuo,Mukaiyama, Teruaki
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p. 658 - 659
(2008/02/07)
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- Immobilized triazine-type dehydrocondensing reagents for carboxamide formation: ROMP-Trz-Cl and ROMP(OH)-Trz-Cl
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New triazine-type dehydrocondensing reagents, such as ROMP-Trz-Cl and ROMP(OH)-Trz-Cl, were synthesized by a ring opening metathesis polymerization (ROMP) method, and these showed higher loading than conventional polymer-supported condensing reagents. The
- Hioki, Kazuhito,Kameyama, Satomi,Tani, Shohei,Kunishima, Munetaka
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p. 825 - 828
(2008/02/08)
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- Development of chlorotriazine polymer dehydrocondensing reagents (Poly-Trzs)
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Polymer-type dehydrocondensing reagents comprising of a triazine dehydrocondensing reagent, itself in a polymerized form (Poly-Trz-MMs'), have been developed by exploiting the chemical properties of cyanuric chloride that readily binds to alcohol or amines. A chlorotriazine polymer bearing two alkoxy substituents at the 4- and 6- positions (Poly-O-Trz-Cl) was prepared by alternating copolymerization between cyanuric chloride and tetra(ethylene glycol). Similarly, polymers bearing both alkoxy and amino substituents (Poly-N-Trz-Cl) were synthesized from tetra(ethylene glycol) bis(4,6-dichlorotriazin-2-yl) ether 6 and tris(2-aminoethyl)amine 7 and/or ethylenediamine 8. All the polymers were shown to be good reagents for dehydrocondensation of carboxylic acids and amines in the presence of NMM, compared to the corresponding monomeric dehydrocondensing reagent (DMT-MM). The advantages of the polymeric reagents are as follows: (1) both the reaction and isolation procedure of dehydrocondensation can be greatly simplified, (2) the dehydrocondensation can be conducted in protic solvents as well as in common organic solvents, (3) the reagents can be efficiently prepared at a low cost, and (4) these reagents are considered eco-friendly, generating a lower amount of waste compared to conventionally related reagents because of high loading of the dehydrocondensing activity (ca. 3 mequiv/g).
- Kunishima, Munetaka,Yamamoto, Kazuyoshi,Hioki, Kazuhito,Kondo, Tomohito,Hasegawa, Masumi,Tani, Shohei
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p. 2604 - 2612
(2007/10/03)
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- An efficient method for the preparation of carboxamides by dehydration condensation using tetrakis(1,1,1,3,3,3-hexafluoro-2-propoxy)silane
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The use of tetraalkoxysilanes, particularly tetrakis(perfluoroalkoxy) silanes, in dehydration condensation of carboxylic acids with amines was investigated. Tetrakis(1,1,1,3,3,3-hexafluoro-2-propoxy)silane, Si[OCH(CF 3)2]4, prepared easily from silicon tetrachloride and sodium 1,1,1,3,3,3-hexafluoro-2-propoxide, was found to be an effective dehydrating reagent for preparing various carboxamides in good to high yields from the corresponding carboxylic acids and amines. Copyright
- Tozawa, Takashi,Yamane, Yoshinobu,Mukaiyama, Teruaki
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p. 1586 - 1587
(2007/10/03)
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- An effective method for the synthesis of carboxamides by using tetrakis(pyridine-2-yloxy)silane as a mild coupling reagent
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Tetrakis(pyridin-2-yloxy)silane [Si(OPy)4] is easily prepared by trans-silylation between silicon tetrachloride and trimethyl(pyridin-2-yloxy) silane in the molar ratio of 1:4. This novel reagent is effectively employed as a mild dehydrating reagent in forming various carboxamides from the corresponding carboxylic acids and amines that involve secondary or tertiary alkyl substituted ones in good to high yields without using any basic promoters such as tertiary amines or 4-(dimethylamino)pyridine. Copyright
- Tozawa, Takashi,Yamane, Yoshinobu,Mukaiyama, Teruaki
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p. 1334 - 1335
(2007/10/03)
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- Development of novel polymer-type dehydrocondensing reagents comprised of chlorotriazines
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A novel immobilized dehydrocondensing reagent comprised of a triazine-type dehydrocondensing reagent itself in a polymerized form was synthesized by copolymerization between tetra(ethylene glycol) bis(dichlorotriazinyl) ether and tris(2-aminoethyl)amine.
- Kunishima, Munetaka,Yamamoto, Kazuyoshi,Watanabe, Yasunobu,Hioki, Kazuhito,Tani, Shohei
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p. 2698 - 2700
(2007/10/03)
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- A convenient method for preparations of 1-acylimidazoles and carboxamides by using novel imidazolylsilane derivatives
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Various imidazolylsilane derivatives were synthesized by a trans-silylation procedure between 1-(trimethylsilyl)imidazoles and chlorosilanes. Among them, tris- and tetrakis(imidazol-1-yl)silane compounds reacted smoothly with free carboxylic acids to form the corresponding 1-acylimidazoles, which subsequently underwent condensation with amines to afford carboxamides in good to high yields. These results indicate that novel reagents containing silicon-imidazole linkage are effectively utilized as dehydrating reagents to form carboxylic acid derivatives from free carboxylic acids and nucleophiles under mild conditions. Copyright
- Tozawa, Takashi,Yamane, Yoshinobu,Mukaiyama, Teruaki
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p. 734 - 735
(2007/10/03)
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- Novel and efficient method for esterification, amidation between carboxylic acids and equimolar amounts of alcohols, and amines utilizing Me2NSO2Cl and N,N-dimethylamines; Its application to the synthesis of coumaperine, a natural chemopreventive dieneamide
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Various carboxylic esters or amides were prepared in good to excellent yield between carboxylic acids and equimolar amounts of alcohols or amines under very mild conditions (0-45°C; within 3 h) using dimethylsulfamoyl chloride (Me2NSO2Cl; 1) combined with N,N-dimethylamines (Me2NR: 2a; R=Me, 2b; R=Bu). The choice of the sulfamoyl chloride and the amine is crucial for the reaction; that is, sterically uncrowded amines accelerated the present esterification and amidation. This agent had some advantages over methanesulfonyl chloride (3)/amines as for the atom-economy, avoidance of side reactions, and had very high chemoselectivity toward the carboxyl group vs the hydroxyl group; the experiment was performed by the addition of 1 to the mixture of carboxylic acids and alcohols. Application of this method to the synthesis of coumaperine, a chemopreventive natural product, was performed using the present amidation as a key step.
- Wakasugi, Kazunori,Nakamura, Atsushi,Iida, Akira,Nishii, Yoshinori,Nakatani, Nobuji,Fukushima, Shoji,Tanabe, Yoo
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p. 5337 - 5345
(2007/10/03)
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- 5,6-DIHYDROPHENANTHRIDIN-5-YL AS AN ACTIVATABLE PROTECTING GROUP OF CARBOXYLIC ACID - A DIRECT PREPARATION OF AMIDES FROM 5-ACYL-5,6-DIHYDROPHENANTHRIDINE
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Various amides are directly prepared from the protected carboxylic acids, 5-acyl-5,6-dihydrophenanthridines, by the reaction with primary amines in the presence of ceric pyridinium chloride and cupric oxide.
- Narasaka, Koichi,Hirose, Takuji,Uchimaru, Tadafumi,Mukaiyama, Teruaki
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p. 991 - 992
(2007/10/02)
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