cas 357336-20-0, brivaracetam | Articles data

Articles about 357336-20-0Total 52 be found

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Chiral resolution method of brivaracetam
The invention relates to a chiral resolution method of brivaracetam. The chiral resolution method comprises the following steps: 1) in a solvent, co-crystallizing a compound (R,S)-2-((R)-2-oxo-4-propyl pyrrolidin-1-yl)butyramide as shown in a formula 2 and D-tartaric acid to obtain a compound as shown in a formula 3; 2) performing alkali dissociation on the compound as shown in the formula 3 to obtain a compound as shown in a formula 1; and 3) carrying out epimerization on the other diastereoisomer compound as shown in the formula 4 in the step 1) under the action of alkali to obtain a compound as shown in the formula 2, and continuously preparing the compound as shown in the formula 1. According to the method, brivaracetam and diastereoisomers can be separated easily and conveniently, so high-purity brivaracetam is prepared.
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Paragraph 0038-0042; 0049-0051; 0058-0060

(2022/01/12)

Intermediate for synthesizing brivaracetam and preparation method thereof
The invention provides an intermediate compound for synthesizing brivaracetam, namely (2S)-2-(5-oxy-3-propyl-2, 5-dihydrofuran-2-yl) amino) butylamide (I), and a preparation method of the intermediatecompound. The compound (I) comprises (S)-2(((R)-5-oxy-3-propyl-2, 5-dihydrofuran-2-yl) amino) butyramide (I)-R, or (S)-2-(((S)-5-oxy-3-propyl-2, 5-dihydrofuran-2-yl) amino) butyramide (I)-S, or a mixture of (I)-R and (I)-S in any proportion. The compound shown in the formula (I) can be used for synthesizing brivaracetam, and a novel method is provided for designing a concise and efficient brivaracetam synthesis route.
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(2021/02/10)

PROCESS FOR THE PREPARATION OF BRIVARACETAM
The present invention relates to a process for the preparation of brivaracetam, a compound of formula I and salts thereof. The present invention also relates to a compound of formula II and a compound of formula IIA, process for its preparation and conversion thereof to brivaracetam, the compound of formula I.
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(2021/06/26)

A NEW COST EFFECTIVE AND SCALABLE PROCESS FOR SYNTHESIZING PURE BRIVARACETAM
The present invention relates to novel, economical processes for the preparation of enantiomerically pure Brivaracetam of Formula I having 99-100% diastereomeric excess (de) from its (R)-lactone intermediate that is (4R)-4-propyldihydrofuran-2(3H)-one.
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(2022/01/05)

Preparation methods of brivaracetam and intermediate thereof
The invention discloses a preparation method of a brivaracetam intermediate as shown in a formula B-R. The preparation method comprises the following steps: reacting a compound as shown in a formula B-P with a resolution reagent to prepare a compound as shown in a formula B-Q; and converting the compound as shown in the formula B-Q into the brivaracetam intermediate as shown in the formula B-R. The resolution reagent is a (1S, 2S)-(+)-1, 2-cyclohexanediamine compound. The invention also provides a preparation method of brivaracetam. According to the methods, a mixture of two diastereoisomers of (S)-2-3-propylpyrrolidine-1-yl butyric acid can be conveniently and effectively split, a chiral chromatographic column is not used, the process time is greatly shortened, the operation is simplified, the process cost is reduced, and industrial production and environmental protection are facilitated.
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Paragraph 0077-0078

(2021/11/03)

Novel preparation process of brivaracetam
The invention relates to the technical field of pharmacy, in particular to a novel brivaracetam preparation process, which utilizes L-2-aminobutanamide and 3-halogenated methylene-hexanoyl halide to directly obtain brivaracetam, avoids the use of a phase transfer catalyst, improves the product yield, simplifies the process steps and improves the production efficiency. The method comprises the following steps: S1, taking R-4-n-propyl-dihydrofuran-2-ketone as a raw material, and carrying out a halogenated acylation reaction in a halogenated acylation solvent to prepare 3-halogenated methylene-hexanoyl halide; S2, by taking the 3-halogenated methylene-hexanoyl halide as a substrate, carrying out reaction and post-treatment in the presence of a single organic solvent without a phase transfer catalyst under an alkaline condition to obtain brivaracetam.
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Paragraph 0013; 0050-0053

(2021/08/11)

Novel preparation method of iracetam
The preparation method comprises the following steps: (R)-4 -propyl dihydrogen -2 (3H) - ketone which is purchased in the market as a raw material under a certain condition, and three-step synthesis of iracetam. To the preparation method provided by the invention, a chiral preparative chromatographic column separation step is not needed, and high optical purity Biracetam can be obtained directly. The method is high in yield. Post-treatment is simple and convenient, low in production cost, is fit for industrial production.
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Paragraph 0021-0027

(2021/10/13)

Novel preparation method of brivaracetam
The invention provides a preparation method of brivaracetam. The preparation method is characterized in that (R)-4-propyldihydro-2(3H)-ketone purchased in the market is used as a raw material to synthesize brivaracetam in four steps under certain conditions. According to the preparation method, a chiral preparative chromatographic column separation step is not needed, and brivaracetam with high optical purity can be directly obtained. The method has the advantages of high yield, simple post-treatment and low production cost, and is suitable for industrial production.
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(2020/11/23)

Preparation method of brivaracetam
The invention provides a preparation method of brivaracetam. The synthesis route of the method is shown in the specification. The preparation method of brivaracetam is simple, economical, environment-friendly and suitable for industrialization.
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(2020/09/30)

ENANTIOSELECTIVE SYNTHESIS OF BRIVARACETAM AND INTERMEDIATES THEREOF
The present invention relates to an improved and economical process for enantioselective synthesis and purification of a novel key intermediate of Brivaracetam. Further, the present invention also relates to a process for the preparation of a chirally pure Brivaracetam of formula I utilizing the said intermediate.
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(2020/07/31)

Preparation method of brivaracetam intermediate
The invention discloses a preparation method of a brivaracetam intermediate shown as B-R. The method comprises the following steps: adding B-P and 1S,2S-diphenylethylenediamine in a solvent, crystallizing, filtering, recrystallizing to obtain B-Q, and converting the B-Q into the B-R. In the preparation process, a chiral chromatographic column is not required to separate isomers, effective components can be separated only by simple steps of extraction, washing, drying, concentration and the like, the separation process is simple, and the production cost of brivaracetam is greatly reduced.
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(2020/07/12)

PROCESS FOR PREPARATION OF BRIVARACETAM INTERMEDIATES AND USE THEREOF
The present invention relates to a process for preparation of antiepileptic agent intermediates. The present invention particularly relates to a process for preparation of Brivaracetam intermediates. The present invention relates to a process for preparation of Brivaracetam compound of Formula (I) or its salts comprising the process for preparation of intermediate compounds.
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(2020/07/31)

Preparation method of brivaracetam intermediate
The invention discloses a preparation method of a brivaracetam intermediate, and provides a brivaracetam intermediate preparation method, which comprises the following step: in water and an organic solvent 1, in the presence of an inorganic weakly-alkaline reagent, carrying out a condensation reaction defined in the specification on a compound represented by a formula III and a compound represented by a formula VI or a salt thereof to obtain a compound represented by a formula IV. According to the preparation method, the raw materials are easy to obtain and low in price; the chiral center of n-propyl on butyrolactam is constructed at the beginning; the intermediate and the product are easy to separate and purify and even do not need to be purified, so that operation is simple; and the highquality and high optical purity product is obtained, wherein the proportion of brivaracetam is greater than 99.5%, and the content of single impurity is less than 0.1%.
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Paragraph 0110-0116

(2020/06/16)

COMPOUNDS AND THEIR USE IN THE SYNTHESIS OF BRIVARACETAM APIS
Provided is a compound of formula III, and also provided are its use and method in the synthesis of Brivaracetam APIs. The raw materials involved in the method are cheap and easy to obtain, and can prepare Brivaracetam APIs with high optical, which avoids chiral separation and tedious separation and purification steps, reduces cost and is more suitable for industrial production.
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(2020/07/25)

Compound, preparation method thereof and application thereof in preparation of brivaracetam
The invention provides a novel brivaracetam intermediate and a preparation method thereof. The intermediate is applied to preparation of brivaracetam. The method has advantages of simple operation, environment-friendliness, high yield and good optical purity.
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Paragraph 0057-0059

(2020/06/09)

Identification, characterization, synthesis and strategy for minimization of potential impurities observed in the synthesis of brivaracetam
A first systematic impurity profile research concerning nine observed and potential process related impurities of antiepileptic drug brivaracetam is reported. Among which three (impurity G/H/I) have not been discovered or reported before, these nine impurities were monitored by HPLC, and their structures were identified on the basis of MS and NMR spectroscopy. In addition to the formation, synthesis, and characterization, strategies for minimizing these impurities to the levels accepted by ICH are also described in this report.
Liao, Shouzhu,Chen, Hongjun,Wang, Guifei,Wu, Shuming,Yang, Zaiyou,Luo, Weihe,Liu, Zhuanfeng,Gao, Xun,Qin, Junhai,Li, Chuan-hua,Wang, Zhongqing
supporting information

(2020/05/25)

Preparation method of brivaracetam
The invention discloses a preparation method of brivaracetam, and belongs to the field of pharmaceutical synthesis chemistry. Aiming at the problems of complex synthesis route, low yield, high cost, and the like of a target compound in the prior art, the invention provides a novel preparation method, which comprises the following steps: 1) carrying out asymmetric reduction on a compound II under the action of a chiral catalyst to obtain a compound III; 2) reacting the compound III with a halogenating reagent to obtain an intermediate namely a compound IV, and 3) reacting the compound IV with L-amino butanamide to obtain a compound I. The method has the advantages of simple process, low production cost, and easy industrial production.
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(2020/08/27)

Synthesis and preparation of brivaracetam
The invention discloses a preparation method of brivaracetam, which comprises the following step: in an organic solvent and under the protection of anhydrous inert gas, one-step synthesis is carried out on a compound A and (S)-2-aminobutanamide to obtain brivaracetam. The preparation method provided by the invention has the advantages of short steps, high yield, simple post-treatment, high purityof the prepared product and low production cost, and is suitable for industrial production.
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Paragraph 0020

(2020/06/09)

Preparation method of brivaracetam and intermediates thereof
The invention discloses compounds as shown in the formulas A and B which are intermediates of brivaracetam and a preparation method of the compounds, and a method of preparing the brivaracetam from the compounds as shown in the formulas A and B.
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Paragraph 0091-0100

(2019/04/17)

Compound, and use thereof in synthesis of brivaracetam bulk drug
The invention provides a compound of formula II, and also provides a use of the compound of formula II in the synthesis of a bovaracetam bulk drug, and a synthesis method of the compound of formula II. The method has the advantages of cheap and easily available involved raw material, preparation of the bovaracetam bulk drug with a high optical purity, avoiding of chiral separation and tedious separation and purification steps, cost reduction, and suitableness for industrial production.
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Paragraph 0245-0247

(2019/11/04)

PROCESS FOR PREPARATION OF BRIVARACETAM
The present invention relates to a process for the preparation of brivaracetam and salts thereof. The present invention provides process for the preparation of brivaracetam and salts thereof with high chiral purity. The present invention provides process for the preparation of brivaracetam and salts thereof wherein the amount of other stereoisomers of brivaracetam is low.
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(2019/05/22)

A west cloth tile tanzania intermediate and west cloth tile tanzania synthetic method (by machine translation)
The invention discloses a west cloth tile tanzania intermediate and west cloth tile tanzania synthesis method, the method comprises removing Carboxyl, then obtained after the hydrogenation reaction of the chiral separation Can be further used for the synthesis of west cloth tile tanzania. The west cloth tile tanzania intermediate synthetic method of this invention, the use of raw materials, the reaction operation is comparatively simple, easy control of reaction conditions. West cloth tile tanzania synthesis method of the present invention, the yield is high, and the synthesized west cloth tile tanzania purity can be up to 99% or more, the overall cost of synthesizing more advantages. (by machine translation)
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Paragraph 0092; 0095; 0096; 0104; 0107; 0108; 0119-0126

(2019/01/23)

Preparation method for brivaracetam intermediate
The invention provides a preparation method for a brivaracetam intermediate. The method comprises the following steps that 1, a solvent, a fourth compound and a Pd/C catalyst are added into a reactionsystem; 2, the reaction system is placed at a hydrogen atmosphere and is subjected to an reaction for 2-3 hours; 3, the reaction is terminated, and filtration and decompression distillation are conducted to obtain the brivaracetam intermediate, namely the compound shown as the formula 3. According to the method, the reaction conditions are mild, the prepared brivaracetam intermediate compound islow in price and suitable for industrialized mass production, and the intermediate low in price is provided for preparation of brivaracetam.
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Paragraph 0099-0105

(2018/04/03)

Preparation method of high chiral purity lactam intermediate and brivaracetam
The invention provides a preparation method of a high chiral purity lactam intermediate. The preparation method of the high chiral purity lactam intermediate specifically includes the steps of: conducting hydrogenation reduction on a formula I compound under the conditions of a catalyst and a chiral inducer to generate a formula II compound with a de value of greater than 98%. The invention also discloses a preparation method of brivaracetam, and the formula II compound can produce a brivaracetam product under an ammoniation condition. The method provided by the invention has the advantages ofsimple operation of process route, low cost, high yield, high chiral purity of product, easy industrial production and the like.
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Paragraph 0053; 0054; 0055

(2018/06/26)

Intermediate compounds for preparing brivaracetam, and preparation method and application thereof
The invention provides intermediate compounds for preparing brivaracetam, and a preparation method and an application thereof. The invention also provides an intermediate compound A and an intermediate compound B and preparation methods thereof, and a synthetic route for preparing the brivaracetam by adopting the intermediate compound B. According to a technical scheme of the invention, the brivaracetam with high quality and high optical purity and intermediates thereof can be obtained; the ratio of the brivaracetam in four optical isomers is more than 99.5%; a silica gel column is not neededto be used for separation and purification; expensive chiral high-performance liquid chromatography is not needed to be used for resolution; complicated separation and purification steps are avoided;the waste of raw materials is avoided; the cost of production is reduced; and the preparation methods provided by the invention are more applicable to industrial production.
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(2019/01/04)

Brivaracetam new intermediate with imidazole ring, and synthesis method and application thereof
The invention discloses a brivaracetam new intermediate with an imidazole ring, and a synthesis method and an application thereof. A structural formula of the brivaracetam new intermediate is shown inthe following formula. The brivaracetam new intermediate is used for synthesizing brivaracetam and is advantageous in that raw materials are cheap and easy to obtain, a reaction route is short, the yield is high, and impurities are less. At the same time, due to introduction of carbonyl imidazole, the problem that center control by HPLC and purity detection of intermediates cannot be carried outin a reaction process is solved.
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Paragraph 0041; 0060-0080; 0086

(2019/01/08)

AN IMPROVED PROCESS FOR THE PREPARATION OF (2S)-2-[(4R)-2-OXO-4-PROPYLTETRAHYDRO-1H-PYRROL-1-YL] BUTANAMIDE AND ITS INTERMEDIATES THEREOF
The present invention relates to an improved process for the preparation of (2S)-2- [(4R)-2-oxo-4-propyltetrahydro-1H-pyrrol-1-yl] butanamide compound of formula- 1, its intermediates, novel salt compounds of intermediates of the compound of formula- 1. Further the use of novel salts in the preparation of the compound of formula- 1. The present invention also relates to the novel process for the preparation of the compound of formula- 1.
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(2019/01/04)

New preparation method of brivaracetam
The present invention relates to a new preparation method of brivaracetam, According to the new preparation method, a chiral compound represented by a formula III and (S)-2-aminobutyramide or a salt thereof are subjected to a condensation reaction in the presence of a condensing agent to obtain a compound represented by a formula IV and having two chiral centers; a hydroxy protecting group R1 is removed to obtain a compound represented by a formula V; the compound represented by the formula V and a chlorinating reagent are subjected to a chlorinating reaction to obtain a compound represented by a formula VI; the compound represented by the formula VI is subjected to a substitution reaction in the presence of an alkaline agent, and ring closure is performed to obtain a formula I. Accordingto the present invention, the structure represented by the formula I contains two chiral centers, the intermediate compound represented by the formula IV has two chiral centers, and the chiral centersare not changed during a series of the reactions until the final product is generated; and with the method, the high optical purity brivaracetam can be directly obtained without the separation with the chiral chromatography, and the method is suitable for industrial production.
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(2018/11/04)

Method for preparing 2-oxo-1-pyrrolidine derivative or salts thereof
The invention discloses a method for preparing a 2-oxo-1-pyrrolidine derivative or salts thereof. The invention particularly relates to the method for preparing the 2-oxo-1-pyrrolidine derivative represented by a formula (I) shown in the description, wherein substituents are as defined in the description. The method disclosed by the invention is simple and feasible, is high in yield and is suitable for industrial production.
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(2018/11/03)

Novel brivaracetam intermediate as well as synthesis method thereof and application
The invention discloses a novel brivaracetam intermediate as well as a synthesis method thereof and application. A structural form of the intermediate is shown in the description. A reaction route forsynthesizing brivaracetam from the intermediate is shown in the description. The novel brivaracetam intermediate disclosed by the invention is used for synthesizing brivaracetam, and has the following beneficial effects: raw materials are cheap and easily available, the reaction route is short, the yield is high, and brivaracetam with high optical purity can be obtained without chiral resolutionor column chromatography separation. According to the brivaracetam synthesis process, the raw materials are cheap and easily available, the reaction route is short, the yield is high, and brivaracetamwith high optical purity can be obtained without chiral resolution or column chromatography separation.
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Paragraph 0052; 0060-0064; 0073-0077; 0086-0090; 0092-0096

(2018/09/11)

Method for preparing lactam compounds with high chiral purity
The invention discloses a method for preparing lactam compounds with high chiral purity. The method for preparing the lactam compounds with the high chiral purity includes steps of adding reactive solvents and heavy metal catalysts into a reaction vessel, and stirring the reactive solvents and the heavy metal catalysts for 10-30 minutes; adding reaction raw materials A into the reaction vessel, then adding hydrogen sources into the reaction vessel and carrying out constant-temperature reaction at the temperature ranging from -30 DEG C to 0 DEG C for 20-40 hours; terminating the reaction, filtering reaction products, and rotationally removing organic solvents from the reaction products; adding water and isopropyl acetate into the reaction products and carrying out extraction; carrying out drying, suction filtration and concentration on organic phase to obtain crude products; re-crystallizing the crude products to obtain lactam products B with high chiral purity. The reduction chiral selectivity can be effectively improved without optional added chiral auxiliaries. The method has the advantages of low production cost, convenience in production and operation, safety, atom economy, easiness in industrial production and the like.
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Paragraph 0030; 0031; 0032

(2018/07/15)

Preparation method of brivaracetam
The invention discloses a preparation method of brivaracetam (formula IV). The preparation method comprises the following steps: carrying out ammonolysis on (R)-4-propyl-dihydrofuran-2-one and (S)-2-amino butyric acid as raw materials to obtain an intermediate II, then carrying out steps of esterification, chlorination and cyclization to obtain an intermediate III, and finally, carrying out an ammonolysis step to obtain the brivaracetam (IV), wherein the steps of esterification, chlorination and cyclization are operated in a combination mode. The preparation method provided by the invention ismild in condition, is simple and convenient to operate, has easily obtained raw materials, and is suitable for large-scale industrial production.
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Paragraph 0022; 0024; 0025; 0027; 0028; 0030

(2019/01/08)

Preparation method of brivaracetam
The invention provides a preparation method of brivaracetam, comprising the steps of (1) aminating, to be specific, dissolving compounds 2 and 3 in solvent 2, and stirring at controlled temperature of10-50 DEG C to allow reacting for 2-3 h, wherein the solvent 2 is one or more of methylbenzene, 1,2-dichloroethane, dichloromethane, trichloromethane and tetrahydrofuran; (2) reducing, to be specific, adding a reducing agent, and allowing reacting at controlled temperature of 10-50 DEG C for 1-4 h, wherein the reducing agent is one or more of sodium borohydride, potassium borohydride and sodium triacetoxyborohydride; (3) performing lactamization, to be specific, allowing reacting at controlled temperature of 20-100 DEG C for 2-5 h, wherein the steps (1) to (3) are performed in inert gas environment. The intermediate compounds of brivaracetam used herein are low in price, and the preparation method has mild reaction conditions and is suitable for industrial large-scale production.
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Page/Page column 8-18

(2018/03/25)

NOVEL PROCESS FOR THE PREPARATION OF BRIVARACETAM
The present invention relates to a cost effective, novel and efficient process for the preparation of Brivaracetam which offers industrially viable, highly pure Brivaracetam in high yields and avoiding chiral resolutions by chromatography and enzymatic resolutions.
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(2018/03/25)

Preparation method of high chiral purity lactam intermediate and brivaracetam
The invention discloses a preparation method of a high chiral purity lactam intermediate and brivaracetam. The preparation method of the lactam intermediate structural formula compound D includes thesteps of: in a solvent, by means of a heavy metal catalyst and a chiral inducer, conducting hydrogenation reduction on a compound C into the lactam intermediate D. The lactam intermediate structural formula compound D provided by the invention can be made into brivaracetam by only one step, the synthesis route is short, the reaction conditions are mild, the post-treatment is simple, the reaction yield is high, the chiral selectivity is good, and the production cost is low. In the reaction process, the conversion rate of the compound C reaches 81%, and the de value of the compound D reaches 99%or more, therefore the method is suitable for industrial production.
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Paragraph 0047-0052

(2018/06/26)

To 2 - (4 - propyl pyrrolidine -2 - one) - butyramide diastereoisomer splitting method
The invention discloses a 2 - (4 - propyl-pyrrolidine - 2 - one) - butyramide two groups of diastereoisomer splitting method. In particular to (2 S, 4 R) - 2 - (4 - propyl-pyrrolidine - 2 - one) - d amide and (2 S, 4 S) - 2 - (4 - propyl-pyrrolidine - 2 - one) - butyramide splitting, or (2 R, 4 R) - 2 - (4 - propyl-pyrrolidine - 2 - one) - d amide and (2 R, 4 S) - 2 - (4 - propyl-pyrrolidine - 2 - one) - butyramide splitting. The invention provides the use of silica gel as the stationary phase splitting method, in order to mix the organic solvent as eluant, can obtain more separation yield is greater than or equal to 90%, optical purity>de 98% of the target compound.
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Paragraph 0038-0047

(2018/07/30)

Synthesis method of drug for treating epilepsy and intermediates thereof
The invention provides a synthesis method of a drug for treating epilepsy and intermediates thereof, and belongs to the field of drug synthesis. A synthesis method of an intermediate (I) comprises a step of carry out condensation reactions between a compound represented by the formula (M1) and L-2-aminobutanamide in the presence of an acid-binding agent. A synthesis method of an intermediate (II) comprises a step of carrying out acylation reactions between the intermediate (I) and an acylation reagent under the effect of a catalyst. The synthesis method of the drug comprises a step of carrying out alkylation reactions between the intermediate (II) and a Grignard reagent under the protection of inert gas and action of a catalyst. The synthesis route is simple, the product can be easily separated and purified, the production cost is low, the synthesis reactions do not need palladium-carbon catalyst, and the method is beneficial for environment protection and industrial production.
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Paragraph 0093-0109

(2018/01/13)

New synthesis method of brivaracetam
The invention provides a synthesis method of brivaracetam. The method adopts cheap and easily available pentanoic acid or valeryl halide as an initial raw material, and provides a brand new synthesis route of a brivaracetam medicine, and the whole reaction route has a high total yield. The method has the advantages of high productivity, low cost, and suitableness for large-scale industrial production.
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(2017/10/13)

2 - oxo - 1 - pyrrolidine chiral derivatives of preparation method (by machine translation)
The invention relates to 2 - oxo - 1 - pyrrolidine chiral derivatives of the preparation method, comprising the following steps: the protection of inert gas in a reaction container under the added chiral catalyst and reaction solvent, stirring 15 - 40min; then the temperature is adjusted to - 80 - 30 °C, are added to a reaction raw material; then, in a reaction container by adding a hydrogen source, then in - 80 - 30 °C constant temperature under the reaction of 8 - 48h; after the reaction, the temperature is adjusted to - 20 - 30 °C, then adding a solution and b substance and then mixing 8 - 12h; then, to the reaction material extraction processing, then the organic layer dried, filtered, concentrated, to get the crude product; then the recrystallization of the crude product, the product is obtained. Preparation method of this invention, has a low production cost, high yield, easy to industrial production and the like. (by machine translation)
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Paragraph 0029-0030

(2017/08/25)

Brivaracetam and preparation method of intermediate thereof
The invention discloses a preparation method of a brivaracetam intermediate shown in B-VI. The preparation method comprises the following steps of dissolving B-IV and R-phenylethylamine into a solvent, crystallizing, filtering, and recrystallizing, so as to obtain B-V; then, converting into B-VI. The preparation method has the advantages that a chiral chromatographic column separation isomer is not needed in the preparation process, and only the simple steps of extraction, washing, drying, concentration and the like are performed, so as to separate effective ingredients; the separation process is simple, and the production cost of brivaracetam is greatly reduced. A formula is shown in the description.
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Paragraph 0078; 0079; 0095; 0096; 0112; 0113; 0129; 0130

(2017/07/19)

PROCESS FOR PREPARING BRIVARACETAM
The present invention relates to a new process for preparing brivaracetam. (Ib)
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Page/Page column 8-9

(2017/06/23)

CONTINUOUS PROCESS FOR PREPARING BRIVARACETAM
The present invention relates to a continuous flow process for preparing brivaracetam.
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Page/Page column 10; 11

(2017/09/02)

Method for preparing brivaracetam
The invention discloses a method for preparing brivaracetam. The method for preparing brivaracetam comprises the following step that in an organic solvent, under the condition of anhydrous and inert gas shielding, a compound V and L-2-aminobutanamide are subjected to a condensation reaction to obtain brivaracetam I. According to the method for preparing brivaracetam, brivaracetam is prepared through only four steps of reacting, the reaction steps are short, the total yield is high, aftertreatment steps and purifying methods are simple, a product with the de value larger than 99.80% can be prepared only through recrystallization, the grade API is reached, the production cost is low, and the method is suitable for industrial production. The formula is shown in the description.
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(2017/05/27)

Preparing method for caproic acid derivative
The invention discloses a preparing method for a caproic acid derivative and provides a preparing method for a caproic acid derivative IV. The method comprises the following steps that in a polar nonprotic organic solvent, a compound III and an iodization reagent are subjected to a nucleophilic substitution reaction under inert gas shielding, and the caproic acid derivative IV is obtained. Brivaracetam can be prepared from the caproic acid derivative IV only through two steps, the synthetic route is short, the reaction condition is mild, posttreatment is simple, the reaction yield is high, and the production cost is low. Racemization does not happen in the reaction process, further purification is conducted through crystallization instead of a chiral high-pressure liquid phase preparing column, the chiral purity of the brivaracetam I can be improved till the de value is larger than 99.80%, meanwhile, the content of other single impurities of the brivaracetam I is smaller than 0.1%, the API level is reached, and the method is suitable for industrial production. The expression is shown in the description.
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(2017/05/27)

A furyl ketone compound preparation method (by machine translation)
The invention discloses a furyl ketone compound. The invention provides a furyl ketone compound III of the preparation method, comprises the following steps: in the solvent, the presence of an inorganic salt, the compound II with a reducing agent to the reduction reaction, to obtain the furyl ketone compound III, the solvent is an aliphatic alcohol solvent or aliphatic alcohol solvent mixed solvent with water. The furyl ketone compound III can be prepared by only three step west cloth tile Tanzania, short synthetic route; compound II ee value is greater than 99.0%, the reaction process is not racemization, obtained crude I west cloth tile Tanzania de value is greater than 99.0%; by crystallization is not chiral high-pressure liquid phase preparation column for further purification, can be I west cloth tile Tanzania chiral purity to further improve to de value 99.80% above, at the same time other shan Zawest cloth tile Tanzania I of less than 0.1%, reach the level of the API, is suitable for industrial production. (by machine translation)
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(2017/08/28)

PROCESSES TO PRODUCE BRIVARACETAM
The present invention provides a scalable synthesis of enantiomerically pure brivaracetam, and related derivatives.
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(2016/12/22)

A Biocatalytic Route to the Novel Antiepileptic Drug Brivaracetam
An asymmetric synthesis of the novel antiepileptic drug Brivaracetam 1 is described. The stereochemistry of the 4-n-propyl substituent is introduced by a biocatalytic resolution of (rac)-methyl 2-propylsuccinate 4-tert-butyl ester 4. The selection of the resolution substrate and the screening of enzymes were carried out from our in-house screening platform. The development and scale-up of the best conditions, including solvent media, pH control, workup, and enzyme supply, led up to a successful demonstration conducted at 1 kg scale in a 10 L vessel. The chiral intermediate (R)-2-propylsuccinic acid 4-tert-butyl ester 6 was reproducibly obtained in 42% yield and 97% ee all along the development. The control of the stereochemistry via the biocatalytic resolution allowed the production of Brivaracetam 1 within the required commercial quality specifications.
Schülé, Arnaud,Merschaert, Alain,Szczepaniak, Christophe,Maréchal, Christophe,Carly, Nicolas,O'Rourke, John,Ates, Célal
p. 1566 - 1575
(2016/09/23)

Process for the preparation of 2-oxo-1-pyrrolidine derivatives
The present invention relates to alternative processes for the preparation of 2-oxo-1-pyrrolidine derivatives of formula (I) Particularly, the present invention relates to alternative processes for the synthesis of levetiracetam, brivaracetam and seletracetam.
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Page/Page column 25

(2010/11/27)

3-CARBOXY- 2-OXO-1 -PYRROLIDINE DERIVATIVES AND THEIR USES
The present invention relates to 3-carboxy-2-oxo-l -pyrrolidine derivatives of formula (I), geometrical isomers, enantiomers, diastereoisomers, pharmaceutically acceptable salts and all possible mixtures thereof, and processes using them.
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Page/Page column 20-21

(2008/06/13)

4-SUBSTITUTED PYRR0LIDIN-2-0NES AND THEIR USE
The present invention relates to optically enriched or substantially optically pure 4-substituted-pyrrolidin-2-ones of formula (III), and their uses for the synthesis of 2-oxo-pyrrolidin-l-yl derivatives.
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Page/Page column 30-31

(2010/11/26)