- An iron variant of the Noyori hydrogenation catalyst for the asymmetric transfer hydrogenation of ketones
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We report the design of a new iron catalyst for the asymmetric transfer hydrogenation of ketones. This type of iron catalyst combines the structural characteristics of the Noyori hydrogenation catalyst (an axially chiral 2,2′-bis(phosphino)-1,1′-binaphthyl fragment and the metal-ligand bifunctional motif) and an ene(amido) group that can activate the iron center. After activation by 8 equivalents of potassiumtert-butoxide, (SA,RP,SS)-7aand (SA,RP,SS)-7bare active but nonenantioselective catalysts for the transfer hydrogenation of acetophenone and α,β-unsaturated aldehydes at room temperature in isopropanol. A maximum turnover number of 14480 was observed for (SA,RP,SS)-7ain the reduction of acetophenone. The right combination of the stereochemistry of the axially chiral 2,2′-bis(phosphino)-1,1′-binaphthyl group and the carbon-centered chiral amine-imine moiety in (SA,RP,RR)-7b′afforded an enantioselective catalyst for the preparation of chiral alcohols with moderate to good yields and a broad functional group tolerance.
- Huo, Shangfei,Wang, Qingwei,Zuo, Weiwei
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supporting information
p. 7959 - 7967
(2020/06/26)
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- waylen apperception HIV reverse transcriptase inhibitors in accordance with the law of the process for the asymmetric synthesis of one-pot synthesis (by machine translation)
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The invention relates to a novel one pot method asymmetric synthesis process of a (S)-6-chlorine-4-cylopropyl ethylnen-4-trifluoromethyl-1,4-dihydro-2H-1,3-benzoxazine-2-ketone (Efavirenz) compound, the compound can be used as an reverse transcriptase inhibitor for human immunodeficiency virus (HIV). The invention also relates to a novel aminoalcohol ligand used for the process.
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Paragraph 0179; 0180; 0181
(2016/10/07)
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- PYRAZOLE CARBOXAMIDE COMPOUNDS, COMPOSITIONS AND METHODS OF USE
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Provided herein are compounds of formula (AA): N N H HN O N N R R 6 A (R a ) p, (AA) stereoisomers or a pharmaceutically acceptable salt thereof, wherein A, R a, p, R and R 6 are defined herein, compositions including the compounds and methods of manufacturing and using the compounds for the treatment of diseases.
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Page/Page column 58
(2014/03/21)
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- Discovery of pyrroloaminopyrazoles as novel PAK inhibitors
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The P21-activated kinases (PAK) are emerging antitumor therapeutic targets. In this paper, we describe the discovery of potent PAK inhibitors guided by structure-based drug design. In addition, the efflux of the pyrrolopyrazole series was effectively reduced by applying multiple medicinal chemistry strategies, leading to a series of PAK inhibitors that are orally active in inhibiting tumor growth in vivo.
- Guo, Chuangxing,McAlpine, Indrawan,Zhang, Junhu,Knighton, Daniel D.,Kephart, Susan,Johnson, M. Catherine,Li, Haitao,Bouzida, Djamal,Yang, Anle,Dong, Liming,Marakovits, Joseph,Tikhe, Jayashree,Richardson, Paul,Guo, Lisa C.,Kania, Robert,Edwards, Martin P.,Kraynov, Eugenia,Christensen, James,Piraino, Joseph,Lee, Joseph,Dagostino, Eleanor,Del-Carmen, Christine,Deng, Ya-Li,Smeal, Tod,Murray, Brion W.
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experimental part
p. 4728 - 4739
(2012/07/28)
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- Enantioselective reduction of α-substituted ketones mediated by the boronate ester TarB-NO2
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A facile and mild reduction procedure is reported for the preparation of chiral secondary alcohols prepared from α-substituted ketones using sodium borohydride and the chiral boronate ester (l)-TarB-NO2. Direct reduction of substituted ketones bearing Lewis basic heteroatoms generally provided secondary alcohols of only modest enantiomeric excess likely due to either competition between the target carbonyl and the functionalized sidechains at the Lewis acidic boron atom in TarB-NO2 or the added steric bulk of the α-sidechain. As an alternative method, these substrates were synthesized using TarB-NO2 via a two-step procedure involving the reduction of an α-halo ketone to a chiral terminal epoxide, followed by regioselective/regiospecific epoxide opening by various nucleophiles. This procedure provides access to a variety of functionalized secondary alcohols including β-hydroxy ethers, thioethers, nitriles, and amines with enantiomeric excesses of 94% and yields up to 98%.
- Eagon, Scott,Ball-Jones, Nicholas,Haddenham, Dustin,Saavedra, Jaime,Delieto, Cassandra,Buckman, Matthew,Singaram, Bakthan
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supporting information; scheme or table
p. 6418 - 6421
(2010/12/30)
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- CARBONYLAMINO PYRROLOPYRAZOLES, POTENT KINASE INHIBITORS
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Carbonylamino Pyrrolopyrazole compounds of formula I, compositions including these compounds and methods of their use are provided. Preferred compounds of formula I have activity as protein kinase inhibitors, including as inhibitors of PAK4.
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Page/Page column 45
(2009/12/28)
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- Ruthenium-catalyzed /V-alkylation of amines and sulfonamides using borrowing hydrogen methodology
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The alkylation of amines by alcohols has been achieved using 0.5 mol percent [Ru(p-cymene)CI2]2 with the bidentate phosphines dppf or DPEphos as the catalyst. Primary amines have been converted into secondary amines, and secondary amines into tertiary amines, including the syntheses of Piribedil, Tripelennamine, and Chlorpheniramine. A/-Heterocyclization reactions of primary amines are reported, as well as alkylation reactions of primary sulfonamides. Secondary alcohols requiremore forcing conditions than primary alcohols but are still effective a lkylating agents in the presence of this catalyst.
- Hamid, M. Haniti S. A.,Allen, C. Liana,Lamb, Gareth W.,Maxwell, Aoife C.,Maytum, Hannah C.,et al.
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supporting information; experimental part
p. 1766 - 1774
(2009/07/25)
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- Catalytic asymmetric borane reduction of prochiral ketones by using (S)-2-(anilinomethyl)pyrrolidine
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Catalytic asymmetric borane reduction of prochiral ketones was examined in the presence of (S)-2-(anilinornethyl)pyrrolidine. Chiral secondary alcohols were obtained with moderate to high enantiomeric excesses (up to 96% ee).
- Hosoda, Naoya,Iogawa, Yoshihiro,Shimada, Yuichi,Asami, Masatoshi
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experimental part
p. 274 - 277
(2009/03/12)
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- Stereoselective Method for the Production of Clopidogrel
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The present invention relates to processes for preparing a compound of the general formula (Ia) wherein X is a halogen atom, or a pharmaceutically acceptable salt thereof, wherein a compound of the formula (II) wherein X is as defined above and Y and Z independently represent a leaving group each, is reacted with an optically active amino alcohol to form a first mixture of diastereomers.
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- Electroreductive generation of (S)-(+)-N,N-dimethyl-2-(hydroxymethyl)- pyrrolidinium mercury compound for enantioselective synthesis of 2-amino-1-alkyl/aryl ethanols
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(S)-(+)-N, N - Dimethyl-2-(hydroxymethyl)-pyrrolidinium (DMHP +)-mercury compound mediated enantioselective reduction of aminomethyl alkyl/aryl ketones in dimethylformamide-2-propanol (9:1) has been carried out using tetrabutylammonium tetrafluoroborate as a supporting electrolyte. The products viz. 2-amino-1-alkyl/aryl ethanols have been obtained in good yield (68-92%) with 35-91% optical purity and have been assigned (S)-configuration. The pinacol (racemic/meso) derivatives are also isolated as minor products (yield 5-20%) via dimerization of radical anion followed by protonation.
- Yadav, Ashok K.,Manju, Meera
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p. 2770 - 2772
(2008/04/18)
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- Highly enantioselective synthesis of β-amino alcohols
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N,N-Dialkyl-β-amino alcohols derived from α-amino acids can be rearranged enantiospecifically by using TFAA/Et3N/NaOH to give 1,2-amino alcohols with enantiomeric excess up to 99%.
- Metro, Thomas-Xavier,Appenzeller, Jerome,Pardo, Domingo Gomez,Cossy, Janine
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p. 3509 - 3512
(2007/10/03)
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- INHIBITORS OF AKT ACTIVITY
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Invented are novel 1 H-imidazo[4,5-c]pyridin-2-yl compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.
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Page/Page column 116
(2008/06/13)
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- Stereoselective process for the preparation of Clopidogrel
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Preparation of (2-halophenyl)(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl) compounds (Ia) or their salts comprises converting benzene derivatives (II) with an optically active amino alcohol to form a first mixture of diastereomers. Preparation of (2-halophenyl)(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl) compounds of formula (Ia) or its salt comprises converting benzene derivatives of formula (II) with an optically active amino alcohol to a first mixture of diastereomers. X : halo; and Y, Z : leaving groups. Independent claims are also included for the following: (1) a mixture of benzene diastereomers of formulae (IVa) and (IVb); (2) a compound (IVa); (3) a mixture of thiazo piperidine diastereomers of formulae (VIa) and (VIb); (4) compound (VIa); (5) a mixture of thiophene diastereomers of formulae (VIIIa) and (VIIIb); (6) a compound (VIIIa); and (7) preparation of 1-dimethylamino-propan-2-ol compound of formula (a) comprising reacting a diastereomeric mixtures of 1-dimethylamino-propan-2-ol of formulae (b) and (c) with L-(-)-di-O-benzoyl-L-(-)-tartaric acid (L-(-)-DBTA) and separating the L-(-)-DBTA salts of the compounds. A* : 1-30C hydrocarbon (containing 5 heteroatoms of S, O, N or halo and substituted with 5 substituents of OH, oxo, CN or nitro group) or one or more optically active units; and either R 1>, R 2>H, 1-20C hydrocarbon containing 4 heteroatoms of S, O, N or halo and substituted with 5 substituents of OH, oxo, CN or nitro groups); or C+R 1>+R 2> or R 1>+R 2>+heteroatom of A* : 5-10 membered ring (optionally saturated and optionally containing further 1-3 heteroatoms of N, O or S adjacent to the N, then a ring member is substituted with up to 5 substituents of 1-6C alkyl, 1-6C alkenyl, 1-6C alkoxy, 5-10C (hetero)aryl, 3-8C cycloalkyl, 2-8C heterocycloalkyl, halo, OH, oxo, CN or nitro (especially 1-6C alkyl, 5-10C hetero(aryl), 3-8C cycloalkyl or 2-8C heterocycloalkyl or N+R 1>+R 2> forms 3-8C saturated or unsaturated ring optionally with 1-6C alkyl or halo substituted and adjacent to N 1-2 further heteroatom of S, N or O). [Image] [Image] [Image] ACTIVITY : Anticoagulant; Thrombolytic. MECHANISM OF ACTION : Thrombocyte aggregation inhibitor.
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Page/Page column 41
(2008/06/13)
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- Chiral tricarbonyl(η6-arene)chromium complexed diphosphanes. Highly enantioselective rhodium-mediated hydrogenation of ketones
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Arenechromium complexed diastereomeric aminophosphine-phosphinite ligands derived from tetrahydroisoquinoline have been synthesised and examined as chiral auxiliaries in the hydrogenation of functionalised ketones. A cyclopentyl-substituted anti-stereoisomer is providing the highest enantioselectivities (up to >99% ee).
- Pasquier, Corinne,Pélinski, Lydie,Brocard, Jacques,Mortreux, André,Agbossou-Niedercorn, Francine
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p. 2809 - 2812
(2007/10/03)
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- Synthesis and application in enantioselective hydrogenation of new free and chromium complexed aminophosphine-phosphinite ligands
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A straightforward synthesis of new free and Cr(CO)3 complexed AMPP ligands (4-7) is described starting from (S)-indoline-2-carboxylic acid. The ligands were applied successfully in the asymmetric hydrogenation of α-functionalized ketones i.e. a ketolactone 8, a ketoamide 9 and an aminoketone 10 leading to the corresponding optically active alcohols in 99, 97, and 99% ee respectively.
- Pasquier, Corinne,Naili, Said,Pelinski, Lydie,Brocard, Jacques,Mortreux, Andre,Agbossou, Francine
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p. 193 - 196
(2007/10/03)
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- α-Nitrogenated organolithium compounds from α-amidomethyl and α-aminomethyl sulfones
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Successive reaction of α-amidomethyl sulfones 7a,b, derived from primary amides, with n-butyllithium and primary alkyl bromides (CH2 = CHCH2Br, CH2 = CMeCH2Br, CH2 = CBrCH2Br, CH ≡ CCH
- Alonso, Diego A.,Alonso, Emma,Najera, Carmen,Ramon, Diego J.,Yus, Miguel
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p. 4835 - 4856
(2007/10/03)
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- AUXILIARY SRTUCTURE AND ASYMMETRIC INDUCTION IN THE "MUKAIYAMA-ALDOL" REACTIONS OF CHIRAL SILYL KETENE ACETALS
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A variety of chiral auxiliaries R*OH were prepared and tested for levels of asymmetric induction control in the "Mukaiyama-aldol" reaction of chiral silyl ketene acetals.Structural features required for high levels of control are discussed.
- Gennari, Cesare,Molinari, Francesco,Cozzi, PierGiorgio,Oliva, Ambrogio
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p. 5163 - 5166
(2007/10/02)
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- Carbon-13 nuclear magnetic resonance spectra of fentanyl analogs
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Natural abundance carbon-13 chemical shifts are reported for the hydrochloride salts of fentanyl and fifteen analogs. The signals are assigned on the basis of chemical shift theory, SFORD multiplicities, signal intensities, comparisons with model compounds, and thiophene carbon-proton coupling constants. In addition to its forensic value, the data suggest that the solution conformations of the analogs are similar to that of fentanyl hydrochloride.
- Brine,Boldt,Huang,Sawyer,Carroll
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p. 677 - 686
(2007/10/02)
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- Asymmetric Synthesis of Pyridylethanols and Amino Alcohols by Enantioselective Reduction with Lithium Borohydride Modified with N,N'-Dibenzoylcystine
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Optically active 1-pyridylethanols and β- and γ-amino alcohols are obtained in high enantiomeric excess from the enantioselective reduction of acetylpyridines and amino ketones using lithium borohydride, N,N'-dibenzoylcystine, and ethanol.
- Soai, Kenso,Niwa, Seiji,Kobayashi, Takashi
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p. 801 - 803
(2007/10/02)
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- Amine Oxidation. Part 16. Kinetic Sudies on the Oxidation of Some Aminoalcohols by Vanadium(V) Ions in Aqueous Perchloric Acid
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The rate of oxidation of aminoalcohols by vanadium(V) ion in aqueous perchloric acid is first order with respect to vanadium(V) and the aminoalcohol.The dependence of the rate on the acidity of the reaction mixture is indicative of the active species bein
- Hutchinson, Richard J.,Smith, John R. Lindsay,Twigg, Martyn V.
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p. 319 - 322
(2007/10/02)
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- Kinetic Resolution of Racemic β-Hydroxy Amines by Enantioselective N-Oxide Formation
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A practical and fairly general procedure for the kinetic resolution of β-hydroxy tertiary amines is described.It involves the selective oxidation of one enantiomer to the N-oxide by using tert-butyl hydroperoxide (TBHP) and a chiral catalyst prepared by mixing 2 parts of titanium isopropoxide (Ti(O-i-Pr)4 and 1.2 parts of either (+)- or (-)-diisopropyl tartrate (DIPT).The product N-oxide and the unreacted amino alcohol are then easily separated by trituration or organic/aqueous solvent extractions, and chromatography is avoided.The oxidations are generally run to 60percent conversion and the results for 21 different amino alcohols are given.The enantiomeric excess of the slow reacting (i.e., recovered) enantiomer of the amino alcohol often exceeds 90percent.Among the more interesting substrates are the natural product ubine (95percent ee) (18), N-methylephedrine (95percent ee) (15), N-methylpseudoephedrine (93percent ee) (16), cis-2-(dimethylamino)cyclohexanol (>95percent ee) (13), trans-2-(dimethylamino)cyclohexanol (92percent ee) (12), N-benzylbevantolol (85percent ee) (27), and N-benzylpropranolol (32percent ee) (21).The latter two examples are β-blocker precursors.One of the most important characteristics of this new route to enantiomerically pure β-hydroxy amines is its predictability.Thus, in all cases examined to date, when using (+)-DIPT the absolute configuration at the carbinol center in the slow reacting enantiomer is always the same .A study of how the titanium/tartrate ratio, water, catalyst/substrate ratio, and temperature effect this reaction is discussed.
- Miyano, Sotaro,Lu, Linda D.-L.,Viti, Steven M.,Sharpless, K. Barry
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p. 4350 - 4360
(2007/10/02)
-
- α-METALLIERTE AMINE DURCH DEPROTONIERUNG ALIPHATISCHER N-METHYLAMINE
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Aliphatic N-methylamines can be deprotonated by means of s-butyllithium/potassium t-butoxide to give dialkylaminomethyl potassium or after metal exchange the more nucleophilic dialkylaminomethyl lithium.
- Ahlbrecht, Hubertus,Dollinger, Horst
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p. 1353 - 1356
(2007/10/02)
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- Asymmetric Synthesis. Part 6. Asymmetric Reduction of Aminoketones with (-)-Bornan-2-exo-yloxyaluminium Dichloride
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α-Dialkylaminoacetophenones and β-dialkylaminopropiophenones have been reduced asymmetrically with (-)-bornan-2-exo-yloxyaluminium dichloride to the corresponding aminoalcohols in 58-92percent enantiomeric excess.The absolute configurations of the predomi
- Samaddar, Ashis K.,Konar, Samir K.,Nasipuri, Dhanonjoy
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p. 1449 - 1451
(2007/10/02)
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