- PROCESS FOR THE PREPARATION OF GAMMA AMINO BUTYRIC ACIDS AND ANALOGS THEREOF
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The present invention relates to a process for the preparation of gamma aminobutyric acid derivatives of formula I, in particular pregabalin, baclofen and analogs thereof. Further, this process is comprised of preparation protocol for compounds of formula I, involving Michael addition and Beckmann rearrangement strategy.
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- Method for preparing pregabalin by photocatalysis (by machine translation)
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The preparation method is characterized by comprising the 3S following -3 - steps:5 - 1) dissolving the compound I and a certain amount of alkali in an organic solvent, adding the compound II, heating the reaction, obtaining the compound III, 2) preparing the compound V; 3) preparing the compound V through deprotection, ring opening, chiral resolution, and recrystallization to obtain pregabalin. The preparation method comprises the following steps: 1) dissolving compound III, compound IV and photocatalyst in an organic solvent. The raw materials used in the invention are cheap and easily available, the reaction conditions of the photocatalytic oxidation method are mild, reagents are environmentally friendly, green and environment-friendly, and the method is an ideal industrial production process. (by machine translation)
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- Preparation method of pregabalin
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The invention discloses a preparation method of pregabalin, and particularly discloses a synthesis method of pregabalin, and relates to a compound shown as a formula I shown in the specification.
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- Synthesis of (+/-)-Pregabalin and its novel lipophilic β-alkyl-substituted analogues from fatty chains
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In this work, were synthesized for the first time a series of new lipophilic β-alkyl substituted GABA derivatives from fatty alkyl chains. The synthesis of these GABA analogues was investigated by two different bicomponent approaches as a key step. The results showed low yields in the path from aliphatic nitroolefins and Meldrum's acid, whereas the Knoevenagel condensation between aliphatic aldehydes and Meldrum's acid afforded fatty alkylidenes in good yields (75-97%). These compounds were subsequently subjected to a conjugate addition reaction with nitromethane, resulting in the fatty Michael adducts (in 87-97% yields) which were in turn submitted to a one pot domino hydrolysis-decarboxylation, leading to the isolation of β-alkyl-substituted γ-nitro acids in good yields (78-92%). Finally, the reduction of the fatty γ-nitro acids allowed for the access to new lipophilic β-alkyl substituted GABA analogues, which were isolated in high yields (90-98%). The new methodology was also applied to the synthesis of antiepileptic drug (+/-)-Pregabalin, which was obtained after four steps in high overall yield. This journal is
- D'Oca, Caroline Da Ros Montes,Mass, Eduardo Bustos,Ongaratto, Renata Fontes,De Andrade, Arthur Motta,D'Oca, Marcelo G. Montes,Russowsky, Dennis
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p. 13230 - 13239
(2020/08/28)
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- Method for preparing 3-aminomethyl-5-methylcaproic acid
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The invention relates to a method for preparing 3-aminomethyl-5-methylcaproic acid, belonging to the technical field of chemistry. According to the preparation method, 3-methyl formate-5-methylhexanoic acid is used as a raw material, and the target product 3-aminomethyl-5-methylcaproic acid can be prepared through two steps of reactions including ammonia ester exchange and reduction. The method has the beneficial effects of simple process route, high product purity of 99.0% or above, less three wastes, no toxic agent, mild reaction conditions and low cost, and is suitable for industrial production.
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Paragraph 0023; 0028-0029; 0031-0032; 0035-0036; 0039
(2020/07/13)
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- Method for preparing 4-isobutyl pyrrolidone by solvent-free method
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The invention discloses a method for preparing 4-isobutyl pyrrolidone by a solvent-free method. The method is characterized in that R-type, S-type or racemic 3-(carbamylmethyl)-5-methylhexanoic acid is used as an initial raw material, 3-aminomethyl-5-methylhexanoic acid is prepared through a Hofmann degradation reaction, and an R-type, S-type or racemic 4-isobutyl pyrrolidone product is prepared through a solvent-free reaction. According to the method, currently prepared sodium hypobromite is used for carrying out the Huffman degradation reaction, so that the defects that sodium hypochlorite is easy to decompose and low in reaction activity can be avoided. The generated 3-aminomethyl-5-methylhexanoic acid is subjected to a melting reaction under the solvent-free condition, pulping and purification are carried out, a small amount of oxidation impurities can be removed, meanwhile, the solid form is improved, finally, suction filtration and drying are carried out, and the 4-isobutyl pyrrolidone product with the purity being 98.5% or above is obtained. In the whole reaction process, less solvent is used, the operation is simple and easy, and the method is clean and environment-friendly.
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Paragraph 0013
(2020/04/02)
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- Method for preparing pregabalin racemate
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The invention belongs to the technical field of organic chemistry, and in particular relates to a method for preparing a pregabalin racemate. The method comprises the following steps: uniformly mixing3-carbamoymethyl-5-methylhexanoic acid and NaOBr, conducting heating with a water bath of 40 to 45 DEG C to enable the system to undergo a process of being automatically heated to 81-85 DEG C due toreaction heat release, and then automatically lowering the temperature to 50-60 DEG C for 1 hour; and heating the reaction system to 80 DEG C for 2 hours. The above automatic temperature raising process facilitates Hoffman rearrangement, thereby increasing the reaction conversion rate and the yield of the pregabalin racemate. The preparation method of the invention is high in yield, good in reproducibility and easy for industrial production.
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Paragraph 0021; 0022; 0023; 0024; 0025; 0026; 0027-0040
(2019/07/11)
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- Organic photocatalysis for the radical couplings of boronic acid derivatives in batch and flow
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We report an acridium-based organic photocatalyst as an efficient replacement for iridium-based photocatalysts to oxidise boronic acid derivatives by a single electron process. Furthermore, we applied the developed catalytic system to the synthesis of four active pharmaceutical ingredients (APIs). A straightforward scale up approach using continuous flow photoreactors is also reported affording gram an hour throughput.
- Lima, Fabio,Grunenberg, Lars,Rahman, Husaini B. A.,Labes, Ricardo,Sedelmeier, Joerg,Ley, Steven V.
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supporting information
p. 5606 - 5609
(2018/06/04)
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- Preparation method of antiepileptic drug-pregabalin
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The invention discloses a preparation method of an antiepileptic drug-pregabalin, belonging to the field of drug synthesis. According to the preparation method, a compound 2 is taken as a raw material, and the pregabalin is prepared by the synthesis steps of enabling the raw material and a Grignard reagent to be subjected to an addition reaction, carrying out deprotection, ring-opening and chiralresolution, and the like. Compared with the methods reported in the existing literatures, the preparation method provided by the invention avoids the use of heavy metal reagents, and is fewer in synthesis steps, higher in process stability, simple to operate and mild in reaction conditions, thus being suitable for large-scale production.
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Paragraph 0009; 0010; 0030; 0032
(2018/04/21)
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- Catalytic Intermolecular Carboamination of Unactivated Alkenes via Directed Aminopalladation
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An intermolecular 1,2-carboamination of unactivated alkenes proceeding via a Pd(II)/Pd(IV) catalytic cycle has been developed. To realize this transformation, a cleavable bidentate directing group is used to control the regioselectivity of aminopalladation and stabilize the resulting organopalladium(II) intermediate, such that oxidative addition to a carbon electrophile outcompetes potential β-hydride elimination. Under the optimized reaction conditions, a broad range of nitrogen nucleophiles and carbon electrophiles are compatible coupling partners in this reaction, affording moderate to high yields. The products of this reaction can be easily converted to free ?3-amino acids and ?3-lactams, both of which are common structural motifs found in drug molecules and bioactive compounds. Reaction kinetics and DFT calculations shed light on the mechanism of the reaction and explain empirically observed reactivity trends.
- Liu, Zhen,Wang, Yanyan,Wang, Zichen,Zeng, Tian,Liu, Peng,Engle, Keary M.
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supporting information
p. 11261 - 11270
(2017/08/22)
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- Synthesis of (±)-Pregabalin by Utilizing a Three-Step Sequential-Flow System with Heterogeneous Catalysts
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(±)-Pregabalin, a γ-amino acid derivative, has been synthesized by utilizing flow methods. A three-step sequential-flow reaction starting from commercial isovaleraldehyde and methyl malonate proceeded smoothly with heterogeneous catalysts to afford the precursor of pregabalin in yields of 75–100 %, and a space-time yield of 52.2 g/L d was reached. In addition, a heterogeneous catalyst for the Knoevenagel reactions of aldehydes with malonates, which is the first step of the synthesis, has been developed. Pregabalin was finally obtained by acid-catalyzed hydrolysis of the precursor followed by neutralization.
- Ishitani, Haruro,Kanai, Kan,Saito, Yuki,Tsubogo, Tetsu,Kobayashi, Shū
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p. 6491 - 6494
(2017/10/18)
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- PROCESS FOR PRODUCING OPTICALLY ACTIVE 4-NITRO-BUTANOIC ACID ESTER AND PREGABALIN
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PROBLEM TO BE SOLVED: To provide a process for producing optically active pregabalin with low number of reaction steps and low cost, as well as to provide a process for producing optically active 4-nitro-butanoic acid ester for use in said process. SOLUTION: Provided is a process for producing optically active 5-methyl-3-nitromethyl-2-alkoxycarbonyl-hexanoic acid alkyl ester by reacting dialkyl malonate and 4-methyl-1-nitro-1-pentene in the presence of a chiral catalyst containing a pyridine bisoxazoline derivative and calcium oxide; and a process for producing pregabalin using the present production process. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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- Method for synthesizing pregabalin from isobutyraldehyde
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The present invention discloses a method for synthesizing pregabalin from isobutyraldehyde. The method comprises the following steps: performing Baylis-Hillman reaction on isobutyraldehyde and acrylonitrile by using DABCO and 2,6-di-tert-butylphenol as catalysts; performing substitution with 1-ethyl chloroformate in a solvent composed of pyridine and dichloroethane; performing carbonylation reaction on CO and ethanol by using palladium acetate and triphenylphosphine as catalysts; performing catalytic hydrogenation on raney nickel; performing hydrolysis in potassium hydroxide and methanol solvent, and adding acid for acid precipitation; and finally performing chiral resolution by using (S)-mandelic acid as a resolving agent. According to the method disclosed by the present invention, the inexpensive and easily available isobutyraldehyde is used as a raw material, and the pregabalin is obtained through Baylis-Hillman reaction, substitution reaction, carbonylation reaction, hydrogenation reaction, hydrolysis and acid precipitation and chiral resolution. The reaction route is simple, and the yield of the whole reaction is relatively high, so that overall yield and purity of the final pregabalin are ensured.
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Paragraph 0016; 0053
(2016/10/08)
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- Method for synthesizing Pregabalin by taking chloroacetonitrile and isobutylaldehyde as raw materials
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The invention discloses a method for synthesizing Pregabalin by taking chloroacetonitrile and isobutylaldehyde as raw materials. The method comprises the steps: carrying out substitution reaction on chloroacetonitrile and trimethyl phosphite in a methanol solvent by taking sodium methoxide as a catalyst; carrying out substitution reaction on the substitution reaction product and 1-ethyl chloroacetate in an ethanol solvent by taking sodium hydroxide as a catalyst; carrying out Wittig-Horner reaction on the substitution reaction product and isobutylaldehyde in a THF solvent by taking sodium hydride as a catalyst; carrying out catalytic hydrogenation by taking Raney nickel as a catalyst; carrying out hydrolysis in a methanol solvent by taking potassium hydroxide as a catalyst, and then, adding acid into hydrolyzate for acid precipitation; and finally, carrying out chiral resolution by taking (S)-mandelic acid as a resolving agent. According to the method, chloroacetonitrile, which is cheap and is readily available, serves as a raw material and is subjected to substitution reaction twice, Wittig-Horner reaction with isobutylaldehyde, catalytic hydrogenation, hydrolyzing acid precipitation and chiral resolution, thereby obtaining Pregabalin. The reaction route is simple, and the yield of reaction of each step is relatively high, so that the total yield and purity of final Pregabalin are guaranteed.
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Paragraph 0048; 0053
(2016/10/08)
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- Method for synthesizing Pregabalin by taking gamma-isobutylglutaric anhydride as intermediate
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The invention discloses a method for synthesizing Pregabalin by taking gamma-isobutylglutaric anhydride as an intermediate. The method comprises the steps: carrying out Knoevenagel condensation on isovaleraldehyde and methyl cyanoacetate in an ethanol solvent by taking piperidine as a catalyst; carrying out Michael addition on the condensation product and diethyl malonate in a n-hexane solvent by taking di-n-propylamine as a catalyst; carrying out hydrolyzing decarboxylation on the addition product under the catalysis of strong acid and under the condition of heating; dehydrating the hydrolyzing decarboxylation product in a THF solvent under the catalysis of phosphorus pentoxide and under the condition of heating; enabling the dehydrated hydrolyzing decarboxylation product to subject to ammonolysis reaction with urea; carrying out Hoffman degradation on the ammonolysis reaction product; and finally, carrying out chiral resolution on the Hoffman degradation product by taking (S)-(+)-mandelic acid as a resolving agent. According to the method, isovaleraldehyde and methyl cyanoacetate, which are cheap and are readily available, serve as raw materials and are subjected to Knoevenagel condensation, Michael addition, acid hydrolyzing decarboxylation and dehydrating, so as to obtain the intermediate gamma-isobutylglutaric anhydride; and the gamma-isobutylglutaric anhydride is subjected to ammonolysis, Hoffman degradation and chiral resolution, thereby obtaining Pregabalin. The reaction route is simple, and the yield of reaction of each step is relatively high, so that the total yield and purity of final Pregabalin are guaranteed.
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-
Paragraph 0064
(2016/10/09)
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- Method for synthesis of pregabalin from methyl cyanoacetate and isovaleraldehyde as raw materials
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The invention discloses a method for synthesis of pregabalin from methyl cyanoacetate and isovaleraldehyde as raw materials. The method comprises that isovaleraldehyde and methyl cyanoacetate undergo a Knoevenagel condensation reaction in an ethanol solvent in the presence of piperidine as a catalyst, the product and diethyl malonate undergo a Michael addition reaction in a n-hexane solvent in the presence of di-n-propylamine as a catalyst, the product undergoes an acid hydrolysis/decarboxylation reaction under conditions of heating and strong acid catalysis, the product and urea undergo an aminolysis reaction, the product undergoes a Hoffman degradation reaction and the product undergoes a chiral resolution reaction in the presence of (S)-(+)-mandelic acid as a resolving agent. Pregabalin is prepared from cheap and easily available isovaleraldehyde and methyl cyanoacetate as raw materials through Knoevenagel condensation, Michael addition, acid hydrolysis/decarboxylation, aminolysis, Hoffman degradation and chiral resolution. The method has a simple reaction route and a high yield in each reaction and guarantees a pregabalin overall yield and purity.
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Paragraph 0015; 0016; 0056
(2016/10/10)
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- Method for synthesizing Pregabalin by taking oxopyrrolidine as intermediate
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The invention discloses a method for synthesizing Pregabalin by taking oxopyrrolidine as an intermediate. The method comprises the steps: carrying out Knoevenagel condensation reaction on isovaleraldehyde and nitromethane in an ethanol solvent by taking piperazine as a catalyst; carrying out Michael addition on the product obtained in the step one and diethyl malonate in an alkaline alcohol solvent; carrying out catalytic hydrogenation on the product obtained in the step two by taking Raney nickel as a catalyst, so as to obtain the oxopyrrolidine intermediate; hydrolyzing the intermediate by taking strong alkali as a catalyst, and then, adding acid into hydrolyzate for acid precipitation; and finally, carrying out chiral resolution by taking (S)-(+)-mandelic acid as a resolving agent. According to the method, isovaleraldehyde and nitromethane, which are cheap and are readily available, serve as raw materials and are subjected to Knoevenagel condensation reaction, Michael addition, hydrogenation reaction, hydrolyzing acid precipitation and chiral resolution, thereby obtaining Pregabalin. The reaction route is simple, and the yield of reaction of each step is relatively high, so that the total yield and purity of final Pregabalin are guaranteed.
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Paragraph 0045
(2016/10/08)
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- Method for synthesizing Pregabalin by taking isovaleraldehyde as raw material
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The invention discloses a method for synthesizing Pregabalin by taking isovaleraldehyde as a raw material. The method comprises the steps: carrying out Knoevenagel condensation on isovaleraldehyde and diethyl malonate in a cyclohexane solvent by taking a mixture of di-n-propylamine and acetic acid as a catalyst; carrying out Michael addition on the product obtained in the step one in an alkaline alcohol solvent; carrying out deacidifying reaction on the product obtained in the step two in a solvent prepared from DMSO and water by taking lithium chloride as a catalyst under the condition of heating; carrying out hydrolytic reaction on the product obtained in the step three under alkaline conditions; carrying out catalytic hydrogenation on the product obtained in the step four by taking Raney nickel as a catalyst; and carrying out chiral resolution on the product obtained in the step five by adopting lipase Lipolase 100T. According to the method, isovaleraldehyde, which is cheap and is readily available, serves as a raw material and is subjected to Knoevenagel condensation reaction, Michael addition, decarboxylation, hydrolysis, hydrogenation reaction and chiral resolution, thereby obtaining Pregabalin. The reaction route is simple, and the yield of reaction of each step is relatively high, so that the total yield and purity of final Pregabalin are guaranteed.
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- PROCESS FOR THE PREPARATION OF PREGABALIN
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The present invention provides an improved process for the preparation of a compound of formula (I), which comprises the steps of: formula (I), (a) reacting isovaleraldehyde of formula (II) and alkyl cyanoacetate of formula (III) optionally in presence of salts of weak acid and weak base or weak base in a suitable solvent to get 2-cyano-5-methyl-hex-2-enoic acid alkyl ester of formula (IV); (b) reacting 2-cyano-5-methyl-hex-2-enoic acid alkyl ester of formula (IV) with a suitable cyanide source in water or in an organic solvent or mixture thereof to get 2-isobutylsuccinonitrile of formula (V); (c) obtaining optionally 2-isobutylsuccinonitrile of formula (V) by reacting isovaleraldehyde of formula (II) and alkyl cyanoacetate of formula (III) in presence of suitable cyanide source in water or in an organic solvent or mixture thereof in single step; (d) converting 2-isobutylsuccinonitrile of formula pa (V) to racemic 3-cyano-5-methyl-hexanoic acid or salt thereof of formula (VI) with a genetically modified nitrilase enzyme (Nit pt 9N_56_2) in water or optionally with an organic co-solvent at appropriate pH and temperature; (e) converting racemic 3-cyano-5-methyl-hexanoic acid or salt thereof of formula (VI) to racemic alkyl 3-cyano-5-methyl-hexanoate of formula (VII) by treatment with alcohol (R3OH) and acidic catalyst or alkyl halide (R3X) in presence of a base in a suitable solvent or a mixture of solvents thereof; (f) obtaining (S)-alkyl 3-cyano-5-methyl-hexanoate of formula (VIII) and (R)-3-cyano-5-methyl-hexanoic acid or salt thereof of formula (X) by enzymatic enantioselective hydrolysis in water or organic solvent or a mixture thereof from racemic alkyl 3-cyano-5-methyl-hexanoate of formula (VII); (g) obtaining optionally the compound of formula (VII) by racemizing unwanted (R)-3-cyano-5-methyl-hexanoic acid or salt thereof of formula (X) or substantially enriched (R)-3-cyano-5-methyl-hexanoic acid salt thereof of formula (X) in presence of a base in organic solvent or a mixture thereof; (h) converting (S)-alkyl 3-cyano-5-methyl-hexanoate of formula (VIII) to pregabalin of formula (I) by hydrolyzing ester group with suitable alkali or alkaline earth metal base followed by hydrogenation optionally in one pot in a solvent selected from water or other organic solvents or a mixture thereof in presence of a suitable hydrogenation catalyst.
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- Pd-Catalyzed C(sp3)-H Carbonylation of Alkylamines: A Powerful Route to γ -Lactams and γ-Amino Acids
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A novel Pd-catalyzed direct C(sp3)-H carbonylation of alkylamines for the synthesis of-lactams and -amino acids has been developed, in which TEMPO was used as the crucial sole oxidant. The synthetic prospect was demonstrated by the concise total synthesis of rac-Pregbalin.
- Wang, Pei-Long,Li, Yan,Wu, Yun,Li, Chao,Lan, Quan,Wang, Xi-Sheng
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supporting information
p. 3698 - 3701
(2015/08/18)
-
- Chemical assembly systems: Layered control for divergent, continuous, multistep syntheses of active pharmaceutical ingredients
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While continuous chemical processes have attracted both academic and industrial interest, virtually all active pharmaceutical ingredients (APIs) are still produced by using multiple distinct batch processes. To date, methods for the divergent multistep continuous production of customizable small molecules are not available. A chemical assembly system was developed, in which flow-reaction modules are linked together in an interchangeable fashion to give access to a wide breadth of chemical space. Control at three different levels - choice of starting material, reagent, or order of reaction modules - enables the synthesis of five APIs that represent three different structural classes (γ-amino acids, γ-lactams, β-amino acids), including the blockbuster drugs Lyrica and Gabapentin, in good overall yields (49-75%).
- Ghislieri, Diego,Gilmore, Kerry,Seeberger, Peter H.
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p. 678 - 682
(2015/03/04)
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- PROCESS AND INTERMEDIATES FOR THE PREPARATION OF PREGABALIN
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The invention provides processes for the manufacture of a compound of formula (IA ). The invention further provides improved methods for the conversion of the compound of formula (I A ) into pregabalin.
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- Carboxylic acids as A traceless activation group for conjugate additions: A three-step synthesis of (±)-pregabalin
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The direct application of carboxylic acids as a traceless activation group for radical Michael additions has been accomplished via visible light-mediated photoredox catalysis. Photon-induced oxidation of a broad series of carboxylic acids, including hydrocarbon-substituted, α-oxy, and α-amino acids, provides a versatile CO2-extrusion platform to generate Michael donors without the requirement for organometallic activation or propagation. A diverse array of Michael acceptors is amenable to this new conjugate addition strategy. An application of this technology to a three-step synthesis of the medicinal agent pregabalin (commercialized by Pfizer under the trade name Lyrica) is also presented.
- Chu, Lingling,Ohta, Chisa,Zuo, Zhiwei,MacMillan, David W. C.
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supporting information
p. 10886 - 10889
(2014/08/18)
-
- Rhodium-catalyzed asymmetric hydroformylation of 1,1-disubstituted allylphthalimides: A catalytic route to β3-amino acids
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The high enantioselective rhodium-catalyzed hydroformylation of 1,1-disubstituted allylphthalimides has been developed. By employing chiral ligand 1,2-bis[(2S,5S)-2,5-diphenylphospholano]ethane [(S,S)-Ph-BPE], a series of β3-aminoaldehydes can be prepared with up to 95% enantioselectivity. This asymmetric procedure provides an efficient alternative route to prepare chiral β3-amino acids and alcohols. Copyright
- Zheng, Xin,Cao, Bonan,Liu, Tang-Lin,Zhang, Xumu
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supporting information
p. 679 - 684
(2013/04/10)
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- PROCESS FOR PREPARING PREGABALIN
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The invention relates to a process for preparing a compound of formula (I): wherein said process comprises hydrogenation of a compound of formula (II); under alkaline conditions, wherein R represents hydrogen or a labile group capable of being converted to hydrogen. The invention also relates to intermediates used in said process, to the use of said intermediates in the preparation of pregabalin and to a process for resolving racemic compounds of formula (I).
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Page/Page column 6
(2012/06/16)
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- PROCESS FOR THE PREPARATION OF R-(-)-3- (CARBAMOYLMETHYL)-5-METHYLHEXANOIC ACID AND THE INTERMEDIATES
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The invention provides a process for resolution of R (±) - 3- (carbamoylmethyl)-5-methylhexanoic acid I to form enantiomerically pure form of compound of formula (I), the said process comprises resolution of racemic mixture of compound of formula (II) with cinchona class of alkaloids or amines. The invention also provides for a process for preparing (S)-3-(aminomethyl)-5- methylhexanoic acid from R (-)-3-(carbamoylmethyl)-5-methylhexanoic acid I.
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- A ring-closing metathesis approach for the synthesis of (±)-pregabalin
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Efficient utilization of a Mannich-type reaction and the ring-closing metathesis (RCM) approach that leads to a convenient synthesis of 3-(aminomethyl)-5-methylhexanoic acid (pregabalin) is described. Springer-Verlag 2011.
- Bobade, Vivek D.,Mhaske, Pravin C.,Vadgaonkar, Kamlesh S.,Shelke, Shivaji H.
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experimental part
p. 847 - 851
(2012/08/27)
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- PROCESS FOR PREPARING PREGABALIN
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The invention relates to a process for preparing a compound of formula (I): wherein said process comprises hydrogenation of a compound of formula (II): under alkaline conditions, wherein R represents hydrogen or a labile group capable of being converted to hydrogen. The invention also relates to intermediates used in said process, to the use of said intermediates in the preparation of pregabalin and to a process for resolving racemic compounds of formula (I).
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Page/Page column 13; 14
(2011/02/24)
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- METHOD FOR PREPARATION OF ENANTIOMERICALLY ENRICHED AND/OR RACEMIC GAMMA-AMINO ACIDS
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A process for preparation of enantiomerically enriched and/or racemic γ-amino acids, particularly those useful for preparing γ-amino acids that exhibit binding affinity to the human α2δ calcium channel subunit, including pregabalin and related compounds such as 3-n-propyl-4-aminobutyric acid.
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Page/Page column 42
(2011/08/04)
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- PROCESS FOR PREPARING PREGABALIN
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Disclosed herein is an improved, commercially viable and industrially advantageous process for the preparation of pregabalin in high yield and purity. The present invention also provides a process for the purification of (S)-pregabalin.
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Page/Page column 4
(2011/10/13)
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- INDUSTRIAL PROCESS FOR THE SYNTHESIS OF (S)-(+)-PREGABALIN
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Process for the preparation of (S)-(+)-pregabalin (1) that racemic pregabalin (2) was solved in water, reacted with a chiral a-hydroxy-carboxylic acid or a mixture of chiral α-hydroxy-carboxylic acids in desired case in the presence of an achiral acid, (S)-(+)-pregabalin (1) was deliberated from the obtained diastereomer salt and in desired case the residue of racemic pregabalin (2) was regenerated.
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Page/Page column 13
(2011/10/31)
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- PROCESS TO PREPARE HIGHLY PURE (S)-PREGABALIN
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A process for the preparation of (S)-pregabalin of formula I containing cyanide ion content less than 5 ppm or free from the cyanide ion,by extracting its cyano diester intermediate of formula III, wherein R11 and R22 are the same or different and are hydrogen, C11-C66 alkyl, aryl, benzyl, substituted benzyl, or C33-C66 cycloalkyl. with an aqueous solution containing a cyanide quenching agent to remove free cyanide ion from the reaction mixture.
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Page/Page column 15
(2010/06/17)
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- PROCESS TO PREGABALIN
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The present invention relates to a novel method for the preparation of racemic pregabalin (1) or a single enantiomer thereof, (S)-(+)-3-(aminomethyl)-5-methyl-hexanoic acid (2).
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Page/Page column 12; 13
(2010/12/31)
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- PREGABALIN -4-ELIMINATE, PREGABALIN 5-ELIMINATE, THEIR USE AS REFERENCE MARKER AND STANDARD, AND METHOD TO PRODUCE PREGABALIN CONTAINING LOW LEVELS THEREOF
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The present invention provides 3- (aminomethyl)-5-methylhex-4-enoic acid (Pregabalin- 4-eliminate or PRG-4E) and 3- (aminomethyl)-5-methylhex-5-enoic acid (Pregabalin-5-eliminate or PRG-5E), and their uses as reference markers and standards for determining the purity of Pregabalin. The invention also provides a method to produce Pregabalin containing low levels of these impurities.
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Page/Page column 18
(2009/05/30)
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- A NOVEL AND EFFICIENT METHOD FOR THE SYNTHESIS OF AN AMINO ACID
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The present invention relates to a novel process for the preparation of γ-amino acids, such 5 as (±)-3-(aminomethyl)-5-methyl-hexanoic acid (1), which is a key intermediate in the preparation of the potent anticonvulsant pregabalin, (S)-(+)-3-(aminomethyl)-5-methyl- hexanoic acid (2), and its analogues.
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Page/Page column 21; 29-30
(2009/12/28)
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- PROCESSES TO PREGABALIN
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The present invention relates to a novel method for the preparation of racemic pregabalin (1) or a single enantiomer thereof, (S)-(+)-3-(aminomethyl)-5-methyl-hexanoic acid (2).
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Page/Page column 25
(2009/07/25)
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- IMPROVED PROCESS FOR PREPARING PREGABALIN
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Disclosed herein is an improved, commercially viable and industrially advantageous process for the preparation of pregabalin in high yield and purity. The present invention also provides a process for the purification of (S)-pregabalin.
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Page/Page column 10
(2009/12/28)
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- PROCESS FOR PREPARING (S)-3-(AMINOMETHYL)-5-METHYLHEXANOIC ACID
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Disclosed herein is a process for the preparing (S)-3-(aminomethyl)-5- methylhexanoic acid by optical resolution of (±)-3-(aminomethyl)-5-methylhexanoic acid and a resolving agent employing a suitable solvent.
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Page/Page column 5-6
(2009/11/29)
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- A NOVEL PROCESS FOR PREPARING PREGABALIN AND ITS ACID ADDITION SALTS
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The present invention provides process for the preparation of novel intermediates of (S)-Pregabalin. The present invention also provides process for the preparation of (S)-Pregabalin or a pharmaceutically acceptable salt or solvate thereof using the intermediates.
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Page/Page column 13
(2008/12/04)
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- A NOVEL PROCESS FOR THE PREPARATION OF PREGABALIN
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The present invention encompasses novel intermediates of pregabalin, namely 3 -cyano-5 -methyl hexanamide (28) and 3-(amino methyl)-5 methyl hexanamide (29), and processes for their preparation. The invention also encompasses a process for converting the novel pregabalin intermediates into pregabalin, Formula (I): The present invention further provides a cost effective method for the synthesis of (S)-pregabalin, which involves the recovery of mandelic acid and tartaric acid used in the resolution process and recycling them, increasing the yields of the final product formed, which substantially reduced the cost of the production.
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Page/Page column 30
(2009/03/07)
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- METHOD AND DEVICE
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A method of providing suspended cells (10) for carrying out biological assays, comprising the steps of: a) providing a frozen cell suspension, b) bringing the frozen cell suspension into direct contact with an excess volume of thawing buffer (12), and c) incubating the solution of step b) at room temperature in order to thaw the cell suspension.
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Page/Page column 18-19
(2008/06/13)
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- POLYMORPHIC FORM I OF PREGABALIN AND PROCESSES FOR ITS PREPARATION
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The present invention relates to novel polymorphic Form I of pregabalin and processes for its preparation. Further provided is an enantiomerically pure pregabalin or salt thereof having less than about 0.03% w/w of the (R)-(?)-enantiomer.
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Page/Page column 3
(2008/06/13)
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- PREGABALIN FREE OF LACTAM AND A PROCESS FOR PREPARATION THEREOF
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The present invention encompasses Pregabalin substantially free of Lactam and a process for obtaining Pregabalin substantially free of Lactam comprising extracting an acidic mixture containing a complex of Pregabalin with a strong mineral acid, with a C3-8 alcohol; and combining the organic phase with an organic base.
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Page/Page column 13-14; 17
(2008/06/13)
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- Prodrugs of GABA analogs, compositions and uses thereof
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The present invention provides prodrugs of GABA analogs, pharmaceutical compositions of prodrugs of GABA analogs and methods for making prodrugs of GABA analogs. The present invention also provides methods for using prodrugs of GABA analogs and methods for using pharmaceutical compositions of prodrugs of GABA analogs for treating or preventing common diseases and/or disorders.
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- Orally administered dosage forms of GABA analog prodrugs having reduced toxicity
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The present invention provides an extended release oral dosage form of prodrugs of gabapentin and other GABA analogs, which dosage forms exhibit reduced toxicity. The dosage forms are particularly useful in administering those prodrugs of gabapentin and other GABA analogs that are metabolized to form an aldehyde. The dosage forms of the invention are useful for treating or preventing diseases and/or disorders for which the parent gabapentin or other GABA analog are known to be therapeutically effective.
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- General synthesis of 3-substituted alkenyl GABA as potential anticonvulsants
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Stereospecific synthesis of cis and trans 3-substituted vinyl-γ- aminobutyric acid analogs were obtained by either a Claisen rearrangement or a Witrig reaction from common diene precursors.
- Serfass, Lucile,Casara, Patrick J.
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p. 2599 - 2602
(2007/10/03)
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