7682-20-4Relevant articles and documents
Synthesis of an analogue of the substance P C-terminal hexapeptide with modification at the glutaminyl and methioninyl residues and increased activity in NK-2 receptor type: Structure-activity relationships
Manolopoulou,Poulos,Tsegenidis
, p. 949 - 954 (1992)
Analogues of [Orn6]-SP6-11 have been synthesized in which the Met11 residue is replaced by Hse(CH3), Hse(Bzl), Nva(5-OCH3), Nva(5-OBzl) and Abu. These analogues were tested in 3 in vitro preparations representative of NK-1, NK-2 and NK-3 receptor types. The Hse(Bzl) analogue is 16.6-fold more potent than the parent hexapeptide at the NK-2 receptor and 2.4-fold more potent at the NK-3 receptor. The Nva(5-OCH3) analogue showed weak antagonist activity in NK-2 and NK-3 receptor types, being a full agonist at NK-1. It is concluded from structure-activity correlations that the role of Met11 side chain in substance P is associated with activity and/or efficacy, as appropriate modifications in the side chain may result either in agonists with increased activity compared to the parent hexapeptide or selective agonists or may induce antagonism.
Preparation method of L-2-aminobutanamide hydrochloride
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Paragraph 0020; 0023; 0029; 0032; 0038; 0041, (2021/06/21)
The invention relates to the technical field of preparation of chiral drug intermediates, and discloses a preparation method of L-2-aminobutanamide hydrochloride, which comprises the following steps: dropwise adding ethyl 2-bromobutyrate into stronger ammonia water, and carrying out chemical reaction in a closed container to prepare a prefabricated mixture; According to the preparation method of the L-2-aminobutanamide hydrochloride, ethyl 2-bromobutyrate is used as an initial raw material, and the medical intermediate L-2-aminobutanamide hydrochloride is prepared through ammonolysis and chiral resolution. Compared with the traditional preparation method, the preparation method adopts a chiral reagent (+)-mandelic acid with low raw material price and racemic 2-aminobutanamide hydrochloride to form diastereoisomers, the L-2-aminobutanamide hydrochloride is obtained through resolution by utilizing the difference of the dissolving properties of the diastereoisomers in ethanol, the optical purity and the chemical purity of the product are high, and the technical scheme has the advantages of mild reaction conditions, short reaction steps, high yield, stable product quality and easy realization of industrial production.
Method for synthesizing medicine for treating epilepsy by using L-2-aminobutanamide hydrochloride
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Paragraph 0048-0053; 0057-0061; 0064-0067; 0071-0074; ..., (2021/11/03)
The invention discloses a method for synthesizing a medicine for treating epilepsy by using L-2-aminobutanamide hydrochloride, and relates to the technical field of medicine synthesis, and the method comprises the following steps: under the protection of nitrogen, adding L-2-aminobutanamide hydrochloride and 4-chlorobutyrate into isopropyl alcohol, and reacting under the action of an alkaline substance and a catalyst, heating and refluxing to carry out nucleophilic substitution reaction and ring-closure reaction to prepare the levetiracetam. According to the method, the levetiracetam is synthesized by adopting a milder alkaline substance and a one-pot method, the operation is simple, the levetiracetam can be prepared without post-treatment, the levetiracetam obtained by the method is low in impurity content and high in chemical purity, the yield can reach 83.43% or above, and the purity reaches 99.6%.
Preparation method of (S)-(+)-2-aminobutanamide hydrochloride
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Paragraph 0032; 0038-0043; 0049-0054; 0060-0065; 0071-0076, (2020/08/02)
The invention discloses a preparation method of (S)-(+)-2-aminobutanamide hydrochloride, and relates to a preparation method of a levetiracetam key intermediate, and the method comprises the followingspecific steps: carrying out esterification reaction on L-2-aminobutyric acid serving as a starting material and thionyl chloride, and concentrating part of solvent after the reaction is finished; introducing ammonia gas to neutralize generated hydrogen chloride and residual thionyl chloride; and filtering, introducing ammonia gas, and carrying out an ammonolysis reaction to obtain the (S)-2-aminobutanamide hydrochloride after the treating is finished. According to the preparation method, the starting material is simple and easy to obtain, the one-pot method is adopted, the atom utilization rate is high, operation is easy and convenient, and the obtained product quality is high.
Method for preparing levetiracetam
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Paragraph 0077; 0080; 0083; 0087; 0089; 0093; 0095; 0099, (2020/02/14)
The invention relates to a method for preparing levetiracetam. The method comprises the following steps: reacting aminobutyric acid in lower alcohol and thionyl chloride to obtain an intermediate I; adding ammonia water to continue the reaction, and adding hydrochloric acid to adjust the pH value to about 3 to salify to obtain a salified intermediate II refined product; reacting the intermediate II in the presence of KOH in the presence of a catalyst and dichloromethane, and then adding 4-chlorobutyryl chloride to continuously react; adding water to hydrolyze, adjusting the pH to be weakly alkaline by using diluted hydrochloric acid, and crystallizing to obtain a levetiracetam crude product; decolorizing and crystallizing in ethyl acetate to obtain a refined product of levetiracetam. The invention also relates to the levetiracetam prepared by the method and pharmaceutical application thereof, for example, the levetiracetam can be used for treating or preventing epilepsy, Parkinson's disease, dyskinesia, migraine, tremor, idiopathic tremor, bipolar disorder, chronic pain, neuropathic pain, or bronchial, asthma or allergic diseases.
Method for preparing levetiracetam
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Paragraph 0112; 0117-0119; 0129; 0133-0134, (2019/01/23)
The invention relates to the technical field of drug synthesis, and provides a method for preparing levetiracetam. The method includes the following steps: taking L-2-aminobutyric acid as a starting material, and preforming esterification with thionyl chloride to obtain (S)-2-methyl aminobutyrate hydrochloride; performing aminolysis reaction between the (S)-2-methyl aminobutyrate hydrochloride andammonia water to generate (S)-2-aminobutylamine hydrochloride; preforming acylation reaction between the(S)-2-aminobutylamine hydrochloride and the mixed solution of 4-chlorobutyryl chloride and dichloromethane; directly performing cyclization reaction between the intermediate product with the dichloromethane and tetrabutyl ammonium bromide to obtain a crude product of levetiracetam; and recrystallizing the crude product to generate the levetiracetam. The preparation method uses the easily-obtained starting material to ensure good reproducibility of the synthesis route, simple unit operationand economic accounting. The reaction in each step is easy to purify, the quality is controllable, and the reaction yield is greatly improved.
Method for synthesizing L-2-aminobutanamide hydrochloride by asymmetric transformation
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Paragraph 0039; 0040; 0041; 0042; 0043; 0044, (2019/05/08)
The invention belongs to the field of pharmaceutical synthesis, and discloses an asymmetric transformation synthesis method of L-2-aminobutanamide hydrochloride. The asymmetric transformation synthesis method comprises the following steps: dissolving DL-aminobutanamide in n-butyric acid; sequentially adding a racemizing agent n-butyraldehyde, L-tartaric acid and a small amount of acetic anhydride;reacting at 115-125 DEG C for 8-10 h to obtain an L-aminobutanamide tartrate complex salt; soaking the L-aminobutanamide tartrate complex salt in ethanol; introducing a hydrogen chloride gas; keepingthe temperature at 20-30 DEG C and reacting for 4 h; and filtering to obtain L-2-aminobutanamide hydrochloride. The method is simple in process operation and environmentally-friendly, the purity of afinal product is up to 99.72% and the yield is up to 95.25%, and industrial production is facilitated.
A Viedma ripening route to an enantiopure building block for Levetiracetam and Brivaracetam
Baglai, Iaroslav,Leeman, Michel,Kellogg, Richard M.,Noorduin, Willem L.
supporting information, p. 35 - 38 (2019/01/04)
A simple route to enantiomerically pure (S)-2-aminobutyramide-the chiral component of the anti-epileptic drugs Levetiracetam and Brivaracetam has been developed. This approach is based on the rational design and application of a Viedma ripening process. The practical potential of the process is demonstrated on a large scale.
A process for preparing 2 - amino ding amide hydrochloride
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Paragraph 0027; 0028; 0030, (2018/03/01)
The invention discloses a method for preparing 2-aminobutanamide hydrochloride. The method comprises the following steps of: reacting 2-aminobutyronitrile with aromatic aldehyde in an alkaline aqueous solution to generate corresponding Schiff base; and hydrolyzing the obtained Schiff base under an acidic condition to obtain 2-aminobutanamide hydrochloride. According to the method disclosed by the invention, the product quality is good, the method is simple to operate, the aftertreatment is convenient, and the process is environment-friendly and is beneficial to industrial production.
Preparation method of (S)-2-aminobutanamide as key intermediate for levetiracetam
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Paragraph 0034; 0035; 0037; 0039, (2018/03/01)
The invention discloses a preparation method of (S)-2-aminobutanamide as a key intermediate for levetiracetam, which belongs to the technical field of drug intermediate synthesis. According to the preparation method disclosed by the invention, a compound 1 undergoes ammonolysis reaction in C1-C3 alkyl alcohol, vacuum concentration is carried out until a dry state is formed after the reaction is complete, an alcoholic solvent is added, ammonia is further injected for freeing, an alcoholic solvent is added for clarification by dissolution after filtration and concentration, crystals are grown after an acidic alcoholic solvent is dripped for salification, a compound 2 is obtained by preparation and purification, wherein X is hydrochloric acid, hydrobromic acid or methanesulfonic acid. The preparation method disclosed by the invention is simple and effective, yield and purity are greatly increased, molar yield is higher than 90 percent, purity is higher than 99.5 percent, a high-quality intermediate is provided for the subsequent preparation of the levetiracetam, the preparation method does not have the step of chiral resolution, and adopts only one type of solvent, recovery is simple,three types of wastes are fewer, and the preparation method meets the requirement of industrial production.
