- METHOD FOR PREPARING PREGABALIN
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The present invention relates to a method for preparing pregabalin by a biological enzyme method. In particular, the method comprises producing pregabalin B and an R-configuration compound C by using a compound A as a raw material under the action of a biological enzyme; performing configuration inversion of the separated and recovered R-configuration compound C under the action of an isomerase to produce an S-configuration compound D; and producing pregabalin B from the compound D under the action of a biological enzyme
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Paragraph 0044; 0047; 0050; 0053; 0056
(2021/04/23)
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- Desymmetrization of Prochiral Cyclobutanones via Nitrogen Insertion: A Concise Route to Chiral γ-Lactams
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Asymmetric access to γ-lactams is achieved via a cyclobutanone ring expansion using widely available (1S,2R)-1-amino-2-indanol for chiral induction. Mechanistic analysis of the key N,O-ketal rearrangement reveals a Curtin–Hammett scenario, which enables a downstream stereoinduction (up to 88:12 dr) and is corroborated by spectroscopic, crystallographic, and computational studies. In combination with an easy deprotection protocol, this operationally simple sequence allows the synthesis of a range of optically pure γ-lactams, including those bearing all-carbon quaternary stereocenters. In addition, the formal synthesis of drug molecules baclofen, brivaracetam, and pregabalin further demonstrates the synthetic utility and highlights the general applicability of the presented method.
- Sietmann, Jan,Ong, Mike,Mück-Lichtenfeld, Christian,Daniliuc, Constantin G.,Wiest, Johannes M.
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p. 9719 - 9723
(2021/03/16)
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- Method for synthesizing and refining (S)- pregabalin (by machine translation)
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The reaction conditions of the method disclosed by the invention are mild, and the method disclosed by the invention is mild in reaction conditions: (S)- kg of crude,methylhexanoic acid is obtained through: degradation, the reaction conditions of the intermediate (R)- (-) - 3 - (isobutyl - 2 2-pyrrolidinone) - 5 - are more moderate, and the reaction conditions of the preparation method, Hoffman are obtained (S)- times by weight, of the preparation method for, pregabalin concentrate (S)- 4 - obtained by hydrolysis-ring; of the raw material, to obtain a high-purity pregabalin intermediate solution (S)- obtained by carrying out hydrolysis (S)- on a crude product with a high purity,methyl.methylhexanoic acid after re-crystallization, to, obtain a high,purity pregabalin product. (by machine translation)
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Paragraph 0041-0044; 0050-0053; 0059-0062
(2020/04/17)
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- Synthetic method of environment-friendly and efficient pregabalin
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The invention relates to a synthetic method of environment-friendly and efficient pregabalin. The synthetic method comprises the following steps: 1) dehydrating and condensing acetate and isopentyl aldehyde to obtain 5-methyl-2-hexenoate; 2) performing cyano addition on the 5-methyl-2-hexenoate to obtain (S)-5-methyl-3-cyanohexanoate; 3) performing hydrogen reduction cyclization on the (S)-5-methyl-3-cyanohexanoate to obtain (S)-4-isobutylpyrrolidin-2-one; and 4) performing hydrolysis and ring opening on the (S)-4-isobutylpyrrolidin-2-one to obtain the pregabalin. The synthetic route has the advantages of cheap and easily available raw materials, few reaction steps, mild process conditions, simple operation, high reaction yield and less environment pollution, and is more suitable for industrial production of bulk drug pregabalin.
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- A process for preparing S - pregabalin in amide method
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The invention provides a S - pregabalin in amide preparation method, the reaction step the reaction accelerator is inexpensive and very easy to obtain, at the same time connected to the water separator separating the pregabalin in the molecule cyclization of water, the reaction substrate to pregabalin thoroughly transformed product in the pregabalin S - amide, the obtained S - pregabalin in the amide product purity can be up to 99% or more, the yield is 94% or more, at the same time the preparation method has simple operation, easy in laboratory operation.
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Paragraph 0022-0037
(2019/07/04)
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- Rhodium-catalyzed asymmetric hydrogenation of β-cyanocinnamic esters with the assistance of a single hydrogen bond in a precise position
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With the assistance of hydrogen bonds, the first asymmetric hydrogenation of β-cyanocinnamic esters is developed, affording chiral β-cyano esters with excellent enantioselectivities (up to 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral GABA-derivatives such as (S)-Pregabalin, (R)-Phenibut, (R)-Baclofen. Interestingly, in this system, the catalyst with a single H-bond donor performs better than that with double H-bond donors, which is a novel discovery in the metalorganocatalysis area.
- Li, Xiuxiu,You, Cai,Yang, Yusheng,Yang, Yuhong,Li, Pan,Gu, Guoxian,Chung, Lung Wa,Lv, Hui,Zhang, Xumu
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p. 1919 - 1924
(2018/02/23)
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- Method for preparing 4-(S)-isobutyl-2-pyrrolidone
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The invention belongs to the technical field of medicinal chemistry, and specifically relates to a preparation method for 4-(S)-isobutyl-2-pyrrolidone. The preparation method comprises the following steps: adding S-pregabalin into an alcohol solvent, controlling a temperature and dropwise adding an acylating reagent, after the completion of dropwise addition, carrying out a temperature-controlledreaction, after the completion of the reaction, carrying out concentration so as to remove the solvent, adjusting the pH value of residues with alkali, carrying out extraction with a solvent so as toobtain pregabalin ester, dissolving the pregabalin ester in an organic solvent, closing a ring under heating, carrying out concentration, and removing the solvent so as to obtain the 4-(S)-isobutyl-2-pyrrolidone. The method provided by the invention has simple operation and high yield; and the 4-(S)-isobutyl-2-pyrrolidone obtained by using the method provided by the invention has high purity and can be used as an impurity reference sample.
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Paragraph 0041
(2018/03/26)
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- Asymmetric Amination of α-Chiral Aliphatic Aldehydes via Dynamic Kinetic Resolution to Access Stereocomplementary Brivaracetam and Pregabalin Precursors
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Over the last decades biocatalysis has emerged as an indispensable and versatile tool for the asymmetric synthesis of active pharmaceutical ingredients (APIs). In this context, especially transaminases (TAs) have been successfully used for the preparation of numerous α-chiral, optically pure amines, serving as important building blocks for APIs. Here we elaborate on the development of transaminases recognizing the α-chiral centre adjacent to an aldehyde moiety with aliphatic residues, opening up concepts for novel synthetic routes to the antiepileptic drugs Brivaracetam and Pregabalin. The transformation proceeded via dynamic kinetic resolution (DKR) based on the bio-induced racemisation of the aldehyde enantiomers, enabling the amination of the racemic substrates with quantitative conversions. Medium, substrate as well as enzyme engineering gave access to both (R)- and (S)-enantiomers of the amine precursors of the stereocomplementary drugs in high optical purity, representing a short route to mentioned APIs. (Figure presented.).
- Fuchs, Christine S.,Farnberger, Judith E.,Steinkellner, Georg,Sattler, Johann H.,Pickl, Mathias,Simon, Robert C.,Zepeck, Ferdinand,Gruber, Karl,Kroutil, Wolfgang
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p. 768 - 778
(2017/12/27)
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- NOVEL PHARMACEUTICAL COMPOSITIONS
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The present invention relates to a pharmaceutical composition comprising a plurality of layered double hydroxide nanoparticles and one or more pharmaceutically acceptable excipients, wherein the at least one aqueously unstable anionic drug compound is intercalated between the layers. The present invention also relates to a process for the preparation of such pharmaceutical compositions, the corresponding layered double hydroxides, as well as methods for their use in stablising unstable anionic drug compounds.
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Paragraph 00133-00135
(2017/07/08)
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- A synthetic γ-amino butyric acid kind of chiral the method for preparing the compound of
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The invention discloses a method for synthesizing a gamma-aminobutyric acid chiral compound. The method comprises the following steps of: adding nitroolefin and malonate to a solvent in the presence of a catalyst A and an additive; carrying out conjugate
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Paragraph 0074; 0080
(2017/03/17)
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- STEREOSELECTIVE REDUCTIVE AMINATION OF ALPHA-CHIRAL ALDEHYDES USING OMEGA-TRANSAMINASES FOR THE SYNTHESIS OF PRECURSORS OF PREGABALIN AND BRIVARACETAM
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The present invention relates to processes comprising a combined racemization and stereoselective reductive amination step in which an aldehyde compound of formula (I) is contacted with an (R)-selective ω-transaminase or an (S)-selective ω-transaminase to racemize the compound of formula (I) and obtain an amine compound of formula (II). These processes are useful for the preparation of precursors of pharmaceutically active agents such as brivaracetam and pregabalin.
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Page/Page column 102; 103
(2016/06/06)
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- MANUFACTURING PROCESS FOR (S)-PREGABALIN
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The present invention relates to a novel manufacturing process and novel intermediates useful in the synthesis of pharmaceutically active compounds of general formula (I) used for treatment of epilepsy, neuropathic pain, anxiety and social phobia. The invention describes preparation of enantiomerically pure (S)-Pregabalin from chiral pyrrolidin-2-one of formula (IV).
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Page/Page column 13-14
(2012/05/20)
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- Process for the preparation of pregabalin
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The present invention provides a new enantioselective method of preparing (S)-3-(aminomethyl)-5-methylhexanoic acid, commonly known as pregabalin. The invention also provides new chiral intermediates useful in the production of pregabalin.
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Page/Page column 10
(2012/03/08)
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- PROCESS FOR THE PREPARATION OF PREGABALIN
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The present invention provides a new enantioselective method of preparing (S)-3-(aminomethyl)-5-methylhexanoic acid, commonly known as pregabalin. The invention also provides new chiral intermediates useful in the production of pregabalin.
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Page/Page column 7
(2012/03/08)
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- Solvent-free organocatalytic Michael addition of diethyl malonate to nitroalkenes: The practical synthesis of Pregabalin and γ-nitrobutyric acid derivatives
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A highly enantioselective synthesis of Pregabalin 1 hydrochloride with good overall yield (44%) and enantioselectivity (98% ee) was described. The key step is an asymmetric Michael addition of equivalent of diethyl malonate and nitroalkene under solvent-f
- Liu, Jin-Ming,Wang, Xin,Ge, Ze-Mei,Sun, Qi,Cheng, Tie-Ming,Li, Run-Tao
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p. 636 - 640
(2011/03/19)
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- NOVEL PREGABALIN INTERMEDIATES AND PROCESS FOR PREPARING THEM AND PREGABALIN
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The present invention provides novel compounds, which are especially useful as intermediates for the preparation of Pregabalin. The invention also relates to process for preparing these intermediates and Pregabalin.
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Page/Page column 30
(2009/05/28)
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- Stereoselective 5-exo-trig radical cyclization in the enantioselective synthesis of Pregabalin
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A practical stereoselective 5-exo-trig radical cyclization procedure was developed in order to prepare enantiomerically pure GABA derivative precursors (4-alkyl-pyrrolidin-2-ones). This procedure allows much more rapid access to optically pure GABA derivatives, such as the powerful antiepileptic agent (S)-(+)-3-aminomethyl-5-methylhexanoic acid (Pregabaline).
- Rodríguez, Verónica,Quintero, Leticia,Sartillo-Piscil, Fernando
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p. 4305 - 4308
(2008/02/12)
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- An efficient synthesis of (S)-3-aminomethyl-5-methylhexanoic acid (Pregabalin) via quinine-mediated desymmetrization of cyclic anhydride
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A highly enantioselective synthesis of (S)-3-aminomethyl-5-methylhexanoic acid 1 (Pregabalin) is reported. The key step of the synthesis is a quinine-mediated ring opening of 3-isobutylglutaric anhydride with cinnamyl alcohol. A Curtius rearrangement and subsequent deprotection provides 1 in high yield and excellent enantiomeric excess.
- Hamersak, Zdenko,Stipetic, Irena,Avdagic, Amir
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p. 1481 - 1485
(2008/02/11)
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- PROCESS FOR MAKING (S)-PREGABALIN
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The invention encompasses processes for the synthesis of (S)-Pregabalin, (S)-(+)-3-(aminomethl)-5-methlhexanoic acid.
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Page/Page column 14
(2008/06/13)
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