- Preparation method of lacosamide
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The invention provides a novel methylation method of a lacosamide synthesis intermediate, which comprises the following steps: methylating a compound I in a reaction solvent at a proper temperature byusing trimethyloxyonium tetrafluoroborate as a methylation reagent under alkaline condition to obtain a methylation product II. The reaction formula is shown in the specification. The method has theadvantages of mild reaction condition, simple post-treatment, green methylation reagent, no high toxicity and high reaction yield, and conforms to the safe and environment-friendly green chemical concept. The method is suitable for laboratory small-scale preparation and large-scale industrial production.
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Paragraph 0033-0034
(2020/07/02)
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- Improved Synthesis and Impurity Identification of (R)-Lacosamide
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An improved synthesis of Lacosamide 1 with high purity has been developed. Critical parameters of each step were identified as well as the impurities generated. Moreover, a creative method to improve chiral purity and stability of the key intermediate (R)-2-amino-N-benzyl-3-methoxypropionamide 10 by forming salt with an achiral acid (phosphoric acid) was discovered to ensure the chiral purity of (R)-Lacosamide. Phosphoric acid was further developed for the deprotection of the Boc group.
- Yang, Anjiang,Hu, Feifei,Li, Zhong,Chen, Mengdi,Cai, Jianguang,Wang, Linghui,Zhang, Tao,Zhao, Chuanmeng,Zhang, Fuli
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p. 818 - 824
(2019/04/01)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF LACOSAMIDE
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The present invention relates to an improved process for the synthesis of (R)- Lacosamide in which free base of O-methyl-N-benzyl-D-Serinamide is not isolated before acylation. The process avoids the use of column chromatography and chiral resolution for the preparation of different stages of Lacosamide.
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Page/Page column 17-18
(2018/04/17)
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- Improved preparation method of modified lacosamide
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The invention discloses an improved preparation method of modified lacosamide, which is simple to operate, high in chiral purity and low in cost. According to the improved preparation method, in step 1, amidation is carried out on amino by utilizing di-tert butyl dicarbonate (Boc for short), wherein conditions are moderate and the chiral purity is high and at least reaches 90 percent or more; in step 4, high-selectivity dimethyl sulfate is used as a methylation reagent; the cost is low and the conditions are moderate; the methylation yield is high and the improved preparation method is more suitable for large-scale application. The improved preparation method has the most important innovation points that the Boc is used as an N-protection agent and a Boc protecting group can be simply and conveniently removed by adding acid and a hydrogenation removal means does not need to be used. Secondly, the low-price dimethyl sulfate is used for carrying out methylation and the conditions are moderate; the methylation yield is high and the improved preparation method is more suitable for large-scale application.
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Paragraph 0036; 0045-0047
(2017/08/31)
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- A raco amide intermediate of methylation method (by machine translation)
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The invention is mainly discloses a synthesis scheme in the process of synthesis of the methylation reaction method, the toxic and carcinogenic, cheap a methylating agent such as methyl benzene sulfonic acid methyl ester and the like as the alkylating agent, using inexpensive alkali such as potassium hydroxide to methylation reaction. The present invention can effectively avoid the generation of the N - methyl impurity, and the productive rate is high, will not produce the racemization, hydroxy has good selectivity, is more suitable for industrial production. (by machine translation)
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Paragraph 0043; 0044; 0046; 0048; 0049
(2017/07/21)
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- A raco amide analogs of the separation method
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The invention discloses a separation method of a lacosamide analogue. The separation method of the lacosamide analogue represented in formula I includes the steps of (a), subjecting a reaction mother solution of the lacosamide analogue to water scrubbing, acid pickling and water scrubbing; (b), steaming to remove an organic solvent by means of vacuum concentration to obtain oily matter; (c), subjecting the oily matter to normal-phase column chromatography or high-performance preparative liquid chromatography to obtain a compound in the formula I. A preparation method of the reaction mother solution of the lacosamide analogue includes the step of subjecting a compound in formula II and a methylation reagent to substitution reaction in a two-phase solvent of the organic solvent and water in the presence of alkali and a phase transfer catalyst so as to obtain the reaction mother solution. The lacosamide analogue represented in the formula I is a necessity for quality control of the lacosamide analogue. By the aid of the separation method, the lacosamide analogue can be separated out efficiently.
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Paragraph 0045; 0081; 0082; 0083; 0084; 0085-0092
(2017/10/11)
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- A raco amide analogs and its preparation method
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The invention discloses a Lacosamide analogue and a preparation method thereof, and provides the Lacosamide analogue shown in a formula (I). The invention further provides the preparation method of the Lacosamide analogue shown in the formula (I), including: subjecting a compound shown in a formula (II) and methylated solution in two-phase solvent of organic solvent and water, and in the presence of alkali and phase transfer catalyst to substitution reaction for 20 to 100 hours, so as to obtain the compound shown in the formula (I). The Lacosamide analogue shown in the formula (I) is a necessity for quality control of Lacosamide; the preparation method can be used for efficiently synthesizing the analogue.
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Paragraph 0085; 0086; 0087
(2017/08/25)
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- A raco amide analogs of the application
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The invention discloses application of a lacosamide analogue to the end point control of a reaction for preparation of a compound as shown in the formula III from a compound as shown in the formula II while the lacosamide analogue serves as a standard substance. The lacosamide analogue is obtained through preparation and separation, and is a related impurity of a lacosamide finished product, wherein the impurity impacts the quality and the yield of a final lacosamide product greatly. Therefore, the lacosamide analogue has a far-reaching significance in application to intermediate quality control and lacosamide end point control.
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Sheet 0083; 0084; 0085
(2017/10/13)
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- A rakow amide preparation method
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A preparing process of lacosamide is disclosed. D-serine is adopted as an initial raw material. The method includes: performing amino protection, performing methylation, condensing with benzylamine under a condition of existence of a carboxyl activator, removing an amino protection group, and performing amidation to obtain the lacosamide. The total yield is higher than 66%. The method is high in yield, simple and convenient to operate, high in product purity and especially suitable for industrial production.
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- 3-Azaspiro[5,5]undecan-2,4-dioxo-3-yl diphenyl phosphate (ASUD-diphenyl phosphate), a new reagent for the synthesis of the N-protected amino acid-ASUD ester
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A new reagent, 3-azaspiro[5,5]undecan-2,4-dioxo-3-yl diphenyl phosphate (ASUD-diphenyl phosphate) is described for the synthesis of N-protected amino acid-ASUD esters which are active esters useful in the synthesis of peptides. This compound was synthesized by reacting N-hydroxy-3-azaspiro[5,5]undecane-2,4-dione (HO-ASUD) with diphenyl chlorophosphate in the presence of a base at room temperature and was obtained in high yields. The ASUD-diphenyl phosphate reagent reacts with N-protected amino acids under mild conditions to give the corresponding ASUD active esters, while preserving the enantiomeric purity of the amino acid. The new reagent is a stable crystalline compound and eliminates the need for DCC, a potent skin allergen, used previously for the synthesis of N-protected amino acid-ASUD ester.
- Rao, B. Leelamaheswara,Nowshuddin, Shaik,Jha, Anjali,Divi, Murali K.,Rao
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p. 487 - 491
(2016/06/06)
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- Chiral pool approach for the synthesis of functionalized amino acids: Synthesis of antiepileptic drug (R)-lacosamide
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An efficient total synthesis of (R)-lacosamide 1 has been achieved from N-Boc-N,O-isopropylidene-l-serinol 2 which could easily be obtained from natural l-serine. Our synthesis of 1 starting from 2 using chiral pool strategy resulted in 54% overall yield.
- Aratikatla, Eswar K.,Bhattacharya, Asish K.
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p. 5802 - 5803
(2015/10/05)
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- PROCESS FOR THE PREPARATION OF LACOSAMIDE USING NOVEL INTERMEDIATES
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The present invention provides an improved and commercial process for the preparation of Lacosamide having formula (I). Further, the present invention also provides the novel intermediate compounds of formula (VI) and (VII) and their process for the preparation. Present process utilizes compound of formula (VI) and (VI)I as key novel intermediates for the preparation of Lacosamide.
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- PROCESS FOR THE SYNTHESIS OF ANTIEPILEPTIC DRUG LACOSAMIDE
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The present invention relates to the improved and efficient process for the synthesis of antiepileptic drug Lacosamide in high enantiopurity (>98% ee) and better yield. More particularly, the present invention relates to improved and efficient, cost effective process for synthesis of desired (R) isomer of Lacosamide starting from commercially available (S)-benzyl glycidyl ether.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF LACOSAMIDE
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The present invention relates to an improved process for the preparation of Lacosamide having formula (I).
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Paragraph 81; 82; 83
(2013/03/26)
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- PROCESS FOR THE PREPARATION OF LACOSAMIDE
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The present invention relates to a novel and improved process for the preparation of lacosamide, wherein the process is a sequential one-pot process.
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Paragraph 0043
(2013/05/08)
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- PROCESS FOR THE PREPARATION OF LACOSAMIDE
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The present invention relates to an improved process for the preparation of Lacosamide of Formula (I), comprising: O-methylating a compound of Formula (V) or a compound of Formula (XX) or a compound of Formula XXII; in the presence of a methylating agent and a base to produce Lacosamide of Formula (I).
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Paragraph 0117
(2013/05/22)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF LACOSAMIDE
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The present invention relates to a novel and improved process for the preparation of lacosamide, wherein the process is a sequential one-pot process.
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Page/Page column 8; 12
(2012/01/14)
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- N-OPTIONALLY SUBSTITUTED ARYL-2-OLIGOMER-3-ALKOXYPROPIONAMIDES
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The invention relates to (among other things) N-optionally substituted aryl- 2-oligomer-3-alkoxypropionamides and compositions comprising the same. A compound of the invention, when administered by any of a number of administration routes, exhibits one or more advantages over corresponding compounds lacking the oligomer.
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Page/Page column 36-37
(2012/05/04)
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- NOVEL POLYMORPH OF LACOSAMIDE
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The present invention provides novel crystalline form of lacosamide, process for its preparation and pharmaceutical compositions comprising it. The present invention also provides a process for the preparation of lacosamide amorphous form.
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Page/Page column 9
(2012/04/23)
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- Intermediate for producing lacosamide and a process for its preparation and conversion to lacosamide
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The invention relates to R)-1-Benzylcarbamoyl-2-hydroxy-ethyl)-carbamic acid tert-butyl ester (compound III) with an ee of greater than 90%. and a process for producing the same
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- Intermediate for producing lacosamide and a process for its preparation and conversion to lacosamide
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The invention relates to ((R)-1-Benzylcarbamoyl-2-hydroxy-ethyl)-carbamic acid tert-butyl ester (compound III) with an ee of greater than 90%. and a process for producing the same.
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- Solid Forms Of An N-(Phenylmethyl)Propanamide Derivative And Processes Of Preparation
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The invention relates to solid forms of the anti-epileptic agent lacosamide (I). The invention also relates to mixtures of solid forms of lacosamide. The invention further relates to mixtures of lacosamide enantiomers crystallized in a conglomerate Form and the use thereof in providing enantiomerically enriched lacosamide, preferably lacosamide enriched with the (R)-enantiomer of lacosamide.
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Page/Page column 7
(2011/02/26)
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- AN IMPROVED PROCESS FOR THE PREPARATION OF LACOSAMIDE
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The present invention relates to an improved process for the preparation of Lacosamide of Formula (I), comprising: O-methylating a compound of Formula (V) or a compound of Formula (XX) or a compound of Formula XXII; in the presence of a methylating agent and a base to produce Lacosamide of Formula (I).
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Page/Page column 26-27
(2011/12/04)
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- First asymmetric synthesis of the antiepileptic drug Lacosamide (Vimpat) based on a hydrolytic kinetic resolution strategy
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An efficient asymmetric synthesis of the new antiepileptic drug, Lacosamide is described in high enantiopurity (>98% ee), using Jacobsen's hydrolytic kinetic resolution strategy as a key step.
- Muthukrishnan,Mujahid,Sasikumar,Mujumdar
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p. 1353 - 1357
(2011/11/29)
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- PROCESS FOR PREPARING (R)-2-ACETAMIDO-N-BENZYL-3-METHOXY-PROPIONAMIDE
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Processes for preparing and purifying (R)-2-acetamido-N-benzyl-3-methoxy- propionamide of formula-1 and intermediates thereof are provided.
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Page/Page column 42
(2011/09/15)
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- IMPROVED SYNTHESIS SCHEME FOR LACOSAMIDE
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The present invention is concerned with an improved method of producing (R)-2-acetamido-N-benzyl-3-methoxypropionamide (lacosamide) comprising the 0-methylation of a compound of formula (I) to produce a compound of formula (I I) in a single step reaction.
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Page/Page column 18
(2010/10/20)
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