- Cinchonium Betaines as Efficient Catalysts for Asymmetric Proton Transfer Catalysis: The Development of a Practical Enantioselective Isomerization of Trifluoromethyl Imines
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We have developed a new class of cinchonium betaine catalysts bearing both a base moiety and an aromatic moiety as an N-substituent of the quinuclidine motif. These cinchonium betaines were found to promote proton transfer catalysis with 1000-5000 turnovers per 24 h, thereby enabling us to realize highly efficient enantioselective isomerization of trifluoromethyl imines to provide a practical access to optically active trifluoromethylated amines.
- Zhou, Xiao,Wu, Yongwei,Deng, Li
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- 1,1,1-Trifluoropropan-2-ammonium triflate enantiomers: stereoselective synthesis and direct use in reaction with epoxides
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A three-step synthesis of enantiomerically enriched 1,1,1-trifluoro-2-propanamine based on the use of a chiral sulfinamide auxiliary is described. The reduction of the geometrically pure Z-sulfinimine (NOE, HOE) with NaBH4 or L-Selectride leads to the corresponding (R)- or (S)-configured amine derivatives (X-ray crystallographic analysis) with 92–96% de. The typical models to explain the stereoselection for these reducing agents fail to rationalize the obtained stereoselectivities, and an in situ imine isomerization is proposed to occur. The direct use of the hydrochloric acid salt (with excess Et3N) of this poorly nucleophilic amine for epoxide opening reactions is not possible due to the higher nucleophilicity of chloride. Hence, a novel triflate salt is introduced, synthesized through ready sulfinamide hydrolysis with trimethylsilyl triflate, which can be used directly, without the need of isolating the pure amine beforehand.
- Packer, Gemma,Malassis, Julien,Wells, Neil,Light, Mark,Linclau, Bruno
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- DEUTERATED ANALOGS OF AN ORGANIC COMPOUND
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Provided are deuterated analogs of a compound and methods of using such deuterated analogs for treating a brain tumor in a patient in need thereof; the treatment comprising administering to the patient a deuterated compound described herein. The deuterated compound may be administered in combination with radiation therapy and/or an additional therapeutic agent.
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Paragraph 0182; 0185
(2020/03/29)
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- Discovery of novel HCV inhibitors: Synthesis and biological activity of 6-(indol-2-yl)pyridine-3-sulfonamides targeting hepatitis C virus NS4B
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A novel series of 6-(indol-2-yl)pyridine-3-sulfonamides was prepared and evaluated for their ability to inhibit HCV RNA replication in the HCV replicon cell culture assay. Preliminary optimization of this series furnished compounds with low nanomolar potency against the HCV genotype 1b replicon. Among these, compound 8c has identified as a potent HCV replicon inhibitor (EC50 = 4 nM) with a selectivity index with respect to cellular GAPDH of more than 2500. Further, compound 8c had a good pharmacokinetic profile in rats with an IV half-life of 6 h and oral bioavailability (F) of 62%. Selection of HCV replicon resistance identified an amino acid substitution in HCV NS4B that confers resistance to these compounds. These compounds hold promise as a new chemotype with anti-HCV activity mediated through an underexploited viral target.
- Zhang, Xiaoyan,Zhang, Nanjing,Chen, Guangming,Turpoff, Anthony,Ren, Hongyu,Takasugi, James,Morrill, Christie,Zhu, Jin,Li, Chunshi,Lennox, William,Paget, Steven,Liu, Yalei,Almstead, Neil,George Njoroge,Gu, Zhengxian,Komatsu, Takashi,Clausen, Valerie,Espiritu, Christine,Graci, Jason,Colacino, Joseph,Lahser, Fred,Risher, Nicole,Weetall, Marla,Nomeir, Amin,Karp, Gary M.
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p. 3947 - 3953
(2013/07/27)
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- Asymmetric synthesis of trifluoromethylated amines via catalytic enantioselective isomerization of imines
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A new approach toward the asymmetric synthesis of optically active trifluoromethylated amines was enabled by an unprecedented, highly enantioselective catalytic isomerization of trifluoromethyl imines with a new chiral organic catalyst. Not only aryl but also alkyl trifluoromethylated amines could be obtained in high enantioselectivities.
- Wu, Yongwei,Deng, Li
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supporting information
p. 14334 - 14337
(2012/10/30)
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- 6-SUBSTITUTED- 2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINES AS 5-HT2C RECEPTOR AGONISTS
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The present invention provides 6-substituted 2,3,4,5-tetrahydro-lH- benzo[d]azepines of Formula (I) as selective 5-HT2C receptor agonists for the treatment of 5-HT2c associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety: R6 D R? N-R" R* where R6 is -(CrC3)alkyl-S-(C0-C3)alkyl-R10, -(C1-C3)alkyl-NR11R12, -(CrC3)alkyl-O- R 13. and other substituents are as defined in the specification.
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Page/Page column 67-68
(2008/06/13)
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- 6-ARYLALKYLAMINO- 2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINES AS 5-HT2C RECEPTOR AGONISTS
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The present invention provides 6-substituted 2,3,4,5-tetrahydro-lH- benzo[d]azepines of Formula (I) as selective 5-HT2c receptor agonists for the treatment of 5-HT2c associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety, where, R6 is -NR10R11, where R10 is substituted phenylalkyl or substituted pyridylalkyl and other substituents are as defined in the specification.
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Page/Page column 95
(2010/11/26)
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- PROCESS FOR PRODUCING OPTICALLY ACTIVE 1-ALKYL-SUBSTITUTED 2,2,2-TRIFLUOROETHYLAMINE
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The present invention relates to a process for producing an optically active 1-alkyl-substituted 2,2,2-trifluoroethylamine, which is an important intermediate of medicines and agricultural chemicals, and which is represented by the formula [3] [in the for
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Page/Page column 13
(2008/06/13)
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- 6-[(SUBSTITUTED)PHENYL]TRIAZOLOPYRIMIDINES AS ANTICANCER AGENTS
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This invention relates to certain 6-[(substituted)phenyl]triazolopyrimidine compounds or pharmaceutically acceptable salts thereof, and compositions containing said compounds or pharmaceutically acceptable salts thereof, wherein said compounds are anti-cancer agents useful for the treatment of cancer in mammals. This invention further relates to a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal and further provides a method for the treatment or prevention of cancerous tumors that express multiple drug resistance (MDR) or are resistant because of MDR, in a mammal in need thereof which method comprises administering to said mammal an effective amount of said compounds or pharmaceutically acceptable salts thereof. The present invention relates to a method of treating or inhibiting the growth of cancerous tumor cells and associated diseases in a mammal in need thereof by promotion of microtubule polymerization which comprises administering to said mammal an effective amount of said compounds and pharmaceutically acceptable salts thereof.
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Page/Page column 68
(2008/06/13)
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- Process for the preparation of 1,1,1-trifluoro-2-aminoalkanes
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An improved process for the preparation of a 1,1,1-trifluoro-2-aminoalkane of formula I wherein R1represents an optionally substituted alkyl group; which comprises hydrogenating the corresponding oxime of formula II wherein R1has the meaning given above and the winding line indicates that the hydroxy group may be in the (E)- or (Z)-position with respect to the trifluoromethyl group, in the presence of Raney nickel and a diluent; the improvement wherein is, that said reaction is carried out in a diluent selected from an alkanol, a cyclic ether and an aromatic hydrocarbon.
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- Process for the preparation of 1,1,1-trifluoro-2-aminoalkanes
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An improved process for the preparation of a 1,1,1-trifluoro-2-aminoalkane of formula I whereinR1 represents an optionally substituted alkyl group;which comprises hydrogenating the corresponding oxime of formula IIwherein R1 has the meaning given above and the winding line indicates that the hydroxy group may be in the (E)- or (Z)-position with respect to the trifluoromethyl group,in the presence of Raney nickel and a diluent;the improvement wherein is, that said reaction is carried out in a diluent selected from an alkanol, a cyclic ether and an aromatic hydrocarbon.
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- Asymmetric fluorine-containing primary amines and their preparation
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The present invention, which is aimed at providing a novel reaction for converting a fluorine-containing carbonyl compound to an asymmetric fluorine-containing primary amine, relates to a method in which a Schiff base obtained by the condensation of a flu
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- Chiral sulfoxide controlled asymmetric additions to C-N double bond. An efficient approach to stereochemically defined α-fluoroalkyl amino compounds
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This paper presents a full account of studies into the asymmetric addition reactions between α-lithium derivatives of enantiomerically pure methyl and benzyl p-tolyl sulfoxides and the N-(p-methoxyphenyl)aldimines, bearing trifluoromethyl, pentafluoroethy
- Bravo, Pierfrancesco,Guidetti, Maurizia,Viani, Fiorenza,Zanda, Matteo,Markovsky, Andrey L.,Sorochinsky, Alexander E.,Soloshonok, Irina V.,Soloshonok, Vadim A.
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p. 12789 - 12806
(2007/10/03)
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- New versatile fluorinated chiral building blocks: Synthesis and reactivity of optically pure α-(fluoroalkyl)-β-sulfinylenamines
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Efficient synthesis of optically pure α-(fluoroalkyl)-β-sulfinyl enamines has been achieved by aza-Wittig reaction of triphenyliminophosphoranes with the corresponding α-fluorinated-α'-sulfinyl ketones. The title compounds 3,4 showed an overwhelming prefe
- Arnone, Alberto,Bravo, Pierfrancesco,Capelli, Silvia,Fronza, Giovanni,Meille, Stefano V.,Zanda, Matteo,Cavicchio, Giancarlo,Crucianelli, Marcello
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p. 3375 - 3387
(2007/10/03)
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- Biomimetic reductive amination of fluoro aldehydes and ketones via [1,3]-proton shift reaction. Scope and limitations
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A systematic study of azomethine-azomethine isomerizations of the N-benzylimines 2, derived from fluorinated aldehydes or ketones and benzylamine, has been made. The results reveal that, in sharp contrast to hydrocarbon analogs, fluorinated imines of 2 in triethylamine solution undergo isomerizations to give the corresponding N-benzylidene derivatives 5 (for 5/2 K > 32) in good isolated yields. The rates of the isomerizations depend on the starting imine structures and increase in the following order: aryl perfluoroalkyl ketimine 2m, per(poly)fluoroalkyl aldimine 2a,d-g, perfluoroaryl aldimine 2h, alkyl perfluoroalkyl ketimine 2i,j. The presence of chlorine or bromine atoms in the α-position to the C=N double bond of the starting imine favors a dehydrohalogenation reaction, giving rise to unsaturated products 6-9. The azomethine-azomethine isomerization was studied and proven to proceed essentially (>98%) intramolecularly with isotope exchange experiments. High chemical yields, the simplicity of the experimental procedure, and the low cost of all reagents employed make this biomimetic transamination of fluorocarbonyl compounds a practical method for preparing fluorine-containing amines of biological interest.
- Ono, Taizo,Kukhar, Valery P.,Soloshonok, Vadim A.
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p. 6563 - 6569
(2007/10/03)
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