- 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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- Industrial preparation method of lacosamide
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The invention relates to an industrial preparation method of lacosamide. Esterification is performed on D-serine for generating D-serine methyl ester hydrochloride; the D-serine methyl ester hydrochloride reacts with acetyl chloride for generating N-acetyl-D-serine methyl ester; the N-acetyl-D-serine methyl ester reacts with benzylamine for obtaining (R)-2-acetamido-N-benzyl-3-hydroxypropionamide;the (R)-2-acetamido-N-benzyl-3-hydroxypropionamide reacts with methyl p-toluenesulfonate under an alkaline condition for obtaining (R)-2-acetamido-N-benzyl-3-methoxypropionamide. The preparation method provide by the invention has relatively mild reaction conditions in each steps; the raw materials are easy to obtain; no high-toxicity reagent is used; a safe and environment-friendly green chemistry idea is met; and the method is suitable for industrial amplification.
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Paragraph 0018; 0023; 0024; 0028
(2018/03/26)
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- Process for the preparation of lacosamide
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A novel process for the preparation of (R)-2-acetamido-N-benzyl-3-methoxypropionamide (Lacosamide) is described. It comprises reacting N-acetyl-D-serine methyl ester with benzylamine catalyzed by a non-nucleophilic base to obtain (R)-2-acetamido-2-N-benzyl-3-hydroxy propionamide followed by its methylation.
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Page/Page column 12; 13
(2016/10/17)
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- NOVEL PROCESS FOR THE PREPARATION OF (R)-N-BENZYL-2-ACETAMIDO-3-METHOXYPROPIONAMIDE
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The invention is a novel process for the preparation of lacosamide by employing novel intermediates of formula III and IV:
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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 0111; 0112
(2013/05/22)
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- Process for producing Lacosamide
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Summary The present invention relates to a method for producing (R)-2-acetamido-N-benzyl-3-methoxypropionamide (lacosamide), by methylation of (R)-2-acetamino-2-N-benzyl-3-hydroxy-propionamide (V), in which the methylation is carried out at a temperature below 20 °C.
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Page/Page column 11
(2012/05/04)
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- Process for Producing Lacosamide
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The present invention relates to a method for producing (R)-2-acetamido-N-benzyl-3-methoxypropionamide (lacosamide), by methylation of (R)-2-acetamino-2-N-benzyl-3-hydroxy-propionamide (V), in which the methylation is carried out at a temperature below 20° C.
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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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- PROCESSES FOR THE PREPARATION OF LACOSAMIDE AND INTERMEDIATES THEREOF
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The invention relates to improved processes for the preparation of lacosamide. The invention also relates to a novel intermediate useful in the preparation of lacosamide. The invention also relates to process for the purification of lacosamide.
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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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- PREPARATION OF LACOSAMIDE
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Processes for preparing lacosamide, for use in pharmaceutical compositions comprising lacosamide.
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Page/Page column 23-24
(2011/11/01)
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- AMINO ACID DERIVATIVES USEFUL TO TREAT STROKE
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The invention provides a therapeutic method for treating or preventing stroke and other ischemic disorders, as well as novel compounds and pharmaceutical compositions useful for carrying out such methods.
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- Amino acid derivatives useful to treat stroke
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The invention provides a therapeutic method for treating or preventing stroke and other ischemic disorders, as well as novel compounds and pharmaceutical compositions useful for carrying out such methods.
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- Anticonvulsant enantiomeric amino acid derivatives
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The present invention is directed to a compound in the R configuration about the asymmetric carbon in the following formula: STR1 pharmaceutical compositions containing same and the use thereof in treating CNS disorders in animals.
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- Synthesis and anticonvulsant activities of (R)-(O)-methylserine derivatives
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Efficient procedures for the synthesis of (R)-N-benzyl-2-amino-3- methoxypropionamide ((R)-3), 2-acetamido-3-methoxypropionic acid (4), and O- methylserine (5) are described beginning from (R)-Cbz-serine ((R)-7). The reactions proceeded with little or no racemization and permitted the synthesis of the potent anticonvulsant (R)N-benzyl-2-acetamido-3- methoxypropionamide ((R)-2). The anticonvulsant activities of 2-4 were determined revealing the surprising activity of (R)-2.
- Andurkar, Shridhar V.,Stables, James P.,Kohn, Harold
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p. 3841 - 3854
(2007/10/03)
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- Synthesis and anticonvulsant activities of N-benzyl-2-acetamidopropionamide derivatives
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Studies have demonstrated that 2-substituted N-benzyl-2-acetamidoacetamides (2) are potent anticonvulsants. A recent investigation has led to the hypothesis that an important structural feature in 2 for maximal anticonvulsant activity is the placement of a small, substituted heteroatom moiety one atom from the C(2) site. This paper validates this hypothesis. Twelve derivatives of N-benzyl-2-acetamidopropionamide have been prepared in which six different heteroatom substituents (chloro, bromo, iodo, oxygen, nitrogen, and sulfur) were incorporated at the C(3) site. Highly potent activities were observed for the two oxygen-substituted derivatives, N-benzyl-2-acetamido-3-methoxypropionamide (18) and N-benzyl-2-acetamido-3-ethoxypropionamide (19). The ED50 values in mice following intraperitoneal (ip) dosing for the maximal electroschock-induced seizure test for 18 and 19 were 8.3 and 17.3 mg/kg, respectively. These values compared favorably to the ED50 value found for phenytoin (ED50 = 6.5 mg/kg). Comparable activities were observed for 18 and 19 upon oral (po) administration to rats (18, ED50 = 3.9 mg/kg; 19, ED50 = 19 mg/kg; phenytoin, ED50 = 23 mg/kg). Evaluation of the individual stereoisomers for 18 demonstrated that the principal anticonvulsant activity resided in the (R)-stereoisomer. The ED50 value for (R)-18 was 4.5 mg/kg, and the ED50 for (S)-18 exceeded 100 mg/kg. This difference in activity for the two stereochemical isomers surpassed comparable values for other members within this class of compounds. The protective indices (PI = TD50/ED50) (where TD50 represents a neurotoxic dose impairing rotorod performance) for (R)-18 in mice (ip) and in rats (po) were 6.0 and > 130, respectively.
- Choi, Daeock,Stables, James P.,Kohn, Harold
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p. 1907 - 1916
(2007/10/03)
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