- Regio- and Stereoselective Palladium-Catalyzed C(sp3)-H Arylation of Pyrrolidines and Piperidines with C(3) Directing Groups
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The selective synthesis of cis-3,4-disubstituted pyrrolidines and piperidines is achieved by a Pd-catalyzed C-H arylation with excellent regio- and stereoselectivity using an aminoquinoline auxiliary at C(3). The arylation conditions are silver free, use a low catalyst loading, and employ inexpensive K2CO3 as a base. Directing group removal is accomplished under new, mild conditions to access amide-, acid-, ester-, and alcohol-containing fragments and building blocks. This C-H arylation protocol enabled a short and stereocontrolled formal synthesis of (-)-paroxetine.
- Antermite, Daniele,Affron, Dominic P.,Bull, James A.
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p. 3948 - 3952
(2018/07/22)
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- Diastereoconvergent Synthesis of (–)-Paroxetine
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A diastereoconvergent approach to (–)-paroxetine from diastereomeric 3,4-epoxy-2-piperidones is reported. For this synthesis, a regioselective and stereodivergent CuI-catalyzed epoxide-ring-opening reaction of epoxyamide precursors to give the 4-(4-fluorophenyl)-2-piperidone skeleton with the correct absolute configuration is crucial. Using CuBr·SMe2 as a catalyst, the epoxide-ring-opening reaction takes place with inversion of configuration; the configuration is retained when CuI is used.
- Chamorro-Arenas, Delfino,Fuentes, Lilia,Quintero, Leticia,Cruz-Gregorio, Silvano,H?pfl, Herbert,Sartillo-Piscil, Fernando
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p. 4104 - 4110
(2017/08/07)
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- CCR2 MODULATORS
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Compounds are provided that are modulators of the CCR2 receptor. The compounds have the general formula (I) and are useful in pharmaceutical compositions, methods for the treatment of diseases and disorders involving the pathologic activtation of CCR2 receptors.
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Paragraph 0187
(2016/12/07)
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- BENZENESULFONAMIDE COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS
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This invention is directed to benzensulfonamide compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment of sodium channel-mediated diseases or conditions, such as pain
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Page/Page column 80
(2013/05/22)
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- PAROXETINE DERIVATIVE
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A compound represented by Formula (1), or a pharmacologically acceptable salt thereof retains the principal therapeutic effect of paroxetine and has an improved CYP inhibitory effect: wherein R1 is a hydrogen atom or C1-6 alkyl group
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Paragraph 0113; 0114; 0115
(2013/08/14)
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- Serotonin transporter (sert) inhibitors for the treatment of depression and anxiety
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The present invention relates to trans-derivatives of formula wherein R1, R2, R3, and the dotted line are as defined herein and to pharmaceutically acceptable acid addition salts thereof. The compounds of formula I are goo
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Page/Page column 15
(2008/06/13)
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- NOVEL BENZO [D] [1,3]-DIOXOL DERIVATIVES
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The present invention relates to an isotopologue of Compound 1 substituted with deuterium at the methylene carbon of the benzodioxol ring. The isotopologues of this invention selective serotonin reuptake inhibitors (SSRIs) and possess unique biopharmaceutical and metabolic properties compared to Compound 1. They may also be used to accurately determine the concentration of Compound 1 in biological fluids and to determine metabolic patterns of Compound 1 and its isotopologues. The invention further provides compositions comprising these deuterated isotopologues and methods of treating diseases and conditions that are responsive to increased neuronal serotonin transmission, alone and in combination with additional agents.
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Page/Page column 55
(2010/11/25)
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- Enantioselective Michael additions to α,β-unsaturated imides catalyzed by a salen-al complex
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(Salen)aluminum complex 1b is an efficient catalyst for the conjugate addition of di- and trisubstituted nitriles to a wide range of acyclic alkyl- and aryl-substituted α,β-unsaturated imides. This new methodology provides access to multifunctional compounds that previously have not been readily accessible in enantioenriched form. Synthetic applications of these products include the preparation of enantiomerically enriched piperidines, as exemplified by an expedient asymmetric catalytic synthesis of (-)-paroxetine. Copyright
- Taylor, Mark S.,Jacobsen, Eric N.
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p. 11204 - 11205
(2007/10/03)
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- Catalytic enantioselective conjugate reduction of lactones and lactams
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A dramatic acceleration of the enantioselective copper-catalyzed conjugate reduction of α,β-unsaturated lactones, lactams, and esters is reported upon addition of alcohol additives. Good to excellent yields and enantioselectivities were realized using a catalyst generated in situ from CuCl2·H2O, t-BuONa, p-tol-BINAP, and PMHS, and this methodology was applied to the synthesis of (-)-Paroxetine.
- Hughes, Gregory,Kimura, Masanari,Buchwald, Stephen L.
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p. 11253 - 11258
(2007/10/03)
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- Enzymatic resolution of trans-4-(4′-fluorophenyl)-3-hydroxymethylpiperidines, key intermediates in the synthesis of (-)-Paroxetine
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Two Candida antarctica lipases catalyze the enantioselective acylation of N-substituted trans-4-(4′-fluorophenyl)-3-hydroxymethylpiperidines in organic solvents. These two lipases show opposite stereochemical preference in these processes. Both enantiomers can be obtained in their optically pure forms. The (3S,4R) isomer, is an intermediate for the synthesis of (-)-Paroxetine.
- De Gonzalo,Brieva,Sanchez,Bayod,Gotor
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p. 8947 - 8953
(2007/10/03)
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- Improved synthesis of paroxetine hydrochloride propan-2-ol solvate through one of metabolites in humans, and characterization of the solvate crystals
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Paroxetine, a potent and selective inhibitor of 5-hydroxytryptamine (serotonin) uptake, was prepared through a piperidine derivative, which was reported to be one of the paroxetine metabolites in humans. Thus, the piperidine derivative was converted to its N-tert-butoxycarbonyl (N-Boc) derivative, which was then converted to N-Boc paroxetine. Paroxetine hydrochloride propan-2-ol (isopropyl alcohol (IPA)) solvate crystals were directly obtained from the N-Boc paroxetine by adding hydrogen chloride to the N-Boc paroxetine IPA solution. The amount of IPA content in the crystals was reduced by drying with a continuous change of powder X-ray diffraction patterns. Other characterizations of the solvate crystals were also conducted.
- Sugi, Kiyoshi,Itaya, Nobushige,Katsura, Tadashi,Igi, Masami,Yamazaki, Shigeya,Ishibashi, Taro,Yamaoka, Teiji,Kawada, Yoshihiro,Tagami, Yayoi,Otsuki, Michiya,Ohshima, Takao
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p. 529 - 536
(2007/10/03)
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- Synthesis of Enantiopure trans-3,4-Disubstituted Piperidines. An Enantiodivergent Synthesis of (+)- And (-)-Paroxetine
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Reaction of (R)-phenylglycinol with methyl 5-oxopentanoate gave either bicyclic lactam cis-1 (the kinetic product) or its isomer trans-1 (under equilibrating conditions) as the major products, which were converted to the corresponding (cis or trans) unsaturated lactams 4 and 5. On treatment with lithium alkyl (or aryl) cyanocuprates, these chiral building blocks undergo conjugate addition to give enantiopure trans-3,4-substituted 2-piperidone derivatives in high yield and stereoselectivity. The synthetic potential of this transformation is illustrated by the synthesis of (+)-femoxetine and the two enantiomers of the known antidepressant paroxetine.
- Amat, Mercedes,Bosch, Joan,Hidalgo, Jose,Canto, Margalida,Perez, Maria,Llor, Nuria,Molins, Elies,Miravitlles, Carles,Orozco, Modesto,Luque, Javier
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p. 3074 - 3084
(2007/10/03)
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- Piperidine derivative and process for preparing the same
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A piperidine derivative, which can be used as an intermediate for pharmaceuticals such as paroxetine useful as antidepressants, represented by the general formula (I): STR1 wherein R1 is hydrogen atom, benzyloxycarbonyl group or tert-butoxycarbonyl group; R2 is hydroxymethyl group, an alkylsulfonyloxymethyl group having an alkyl moiety of 1 to 2 carbon atoms, phenylsulfonyloxymethyl group which may have methyl group at the 4-position, (3,4-methylenedioxyphenyl)oxymethyl group, carboxyl group or --CO2 R7 group in which R7 is an alkyl group having 1 to 5 carbon atoms, and Z is methylene group or carbonyl group.
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