33643-46-8Relevant articles and documents
LONG-ACTING INJECTABLE FORMULATIONS OF KETAMINE PAMOATE SALTS
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Page/Page column 12; 13, (2021/06/26)
Provided are sustained-release pharmaceutical compositions including a ketamine pamoate salt and a pharmaceutically acceptable carrier thereof. The compositions include aqueous suspension, solution and matrix delivery system, which can provide sustained release for anesthesia, analgesia or treatment of central nervous system and anti-inflammatory diseases.
Cycloalkyl-Diamines for the Treatment of Pain
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Paragraph 0175-0180, (2021/02/26)
The invention is directed to a method of treatment for pain, the method comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof.
Racemization method of ketamine and derivative or salt thereof
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Paragraph 0113; 0114, (2021/02/20)
The invention discloses a racemization method of ketamine and a derivative or salt thereof. The racemization method comprises the following step: in a solvent, under the action of a catalyst and at the reaction temperature of 110-200 DEG C, carrying out a
Preparation method of ketamine and synthesis method of intermediate compound
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Paragraph 0051; 0052; 0053, (2020/03/12)
The invention discloses an intermediate compound II for synthesizing ketamine, and the chemical structural formula of the intermediate compound II is disclosed in the invention. The compound II is directly synthesized by one-step reaction of a compound under the action of iodobenzene acetate and azidotrimethylsilane; and ketamine is synthesized from the compound II through two steps: 1) reducing azide into amino; and 2) carrying out aminomethylation reaction. Compared with the prior art, the HPLC purity of the product can reach 97% or above, meanwhile, the ketamine prepared through the methodis high in industrialization degree, the quality of the product is greatly improved, intermediate impurities do not exist, the process route is easy to operate, the cost is low, and conditions are mild.
Process Research and Impurity Control Strategy of Esketamine
Gao, Shenghua,Gao, Xuezhi,Yang, Zhezhou,Zhang, Fuli
, p. 555 - 566 (2020/05/19)
An improved synthesis of (S)-ketamine (esketamine) has been developed, which was cost-effective, and the undesired isomer could be recovered by racemization. Critical process parameters of each step were identified as well as the process-related impurities. The formation mechanisms and control strategies of most impurities were first discussed. Moreover, the (S)-ketamine tartrate is a dihydrate, which was disclosed for the first time. The practicable racemization catalyzed by aluminum chloride was carried out in quantitative yield with 99% purity. The ICH-grade quality (S)-ketamine hydrochloride was obtained in 51.1% overall yield (14.0% without racemization) by chiral resolution with three times recycling of the mother liquors. The robust process of esketamine could be industrially scalable.
KETAMINE FORMULATION FOR SUBCUTANEOUS INJECTION
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Paragraph 359, (2020/11/30)
Provided herein are subcutaneous formulations of ketamine that are useful for treating a variety of disease and disorders. The subcutaneous ketamine formulations provided herein reduce injection site irritation and pain.
Determination of the chiral status of different novel psychoactive substance classes by capillary electrophoresis and β-cyclodextrin derivatives
H?gele, Johannes S.,Hubner, Eva-Maria,Schmid, Martin G.
, p. 1191 - 1207 (2020/07/21)
Besides the abuse of well-known illicit drugs, consumers discovered new synthetic compounds with similar effects but minor alterations in their chemical structure. Originally, these so-called novel psychoactive substances (NPS) have been created to circumvent law of prosecution because of illicit drug abuse. During the past decade, such compounds came up in generations, the most popular compound was a synthetic cathinone derivative named mephedrone. Cathinones are structurally related to amphetamines; to date, more than 120 completely new derivatives have been synthesized and are traded via the Internet. Cathinones possess a chiral center; however, only little is known about the pharmacology of their enantiomers. However, NPS comprise further chiral compound classes such as amphetamine derivatives, ketamines, 2-(aminopropyl)benzofurans, and phenidines. In continuation of our project, a cheap and easy-to-perform chiral capillary zone electrophoresis method for enantioseparation of cathinones presented previously was extended to the aforementioned compound classes. Enantioresolution was achieved by simply adding native β-cyclodextrin, acetyl-β-cyclodextrin, 2-hydroxypropyl-β-cyclodextrin, or carboxymethyl-β-cyclodextrin as chiral selector additives to the background electrolyte. Fifty-one chiral NPS served as analytes mainly purchased from online vendors via the Internet. Using 10 mM of the aforementioned β-cyclodextrins in a 10 mM sodium phosphate buffer (pH 2.5), overall, 50 of 51 NPS were resolved. However, chiral separation ability of the selectors differed depending on the analyte. Additionally, simultaneous enantioseparations, the determination of enantiomeric migration orders of selected analytes, and a repeatability study were performed successfully. It was proven that all separated NPS were traded as racemic mixtures.
SYNTHETIC METHODS OF PREPARING ESKETAMINE
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Page/Page column 30, (2020/10/27)
The present invention is directed to methods for the asymmetric synthesis of esketamine. The present invention is further directed to key intermediates in the asymmetric esketamine synthesis. In one embodiment, the invention is an asymmetric synthesis of esketamine comprising the conversion of (S)-2'-chloro-2-methoxy-3,4,5,6-5 tetrahydro-[1,1'-biphenyl]-3-yl carbamate to (S)-2'-chloro-1-isocyanato-6-methoxy- 1,2,3,4-tetrahydro-1,1'-biphenyl.
Synthesis of ketamine from a nontoxic procedure: a new and efficient route
Fareghi-Alamdari, Reza,Momeni-Fard, Behnaz,Zekri, Negar
, (2020/10/02)
Abstract: Ketamine [2-(2-chlorophenyl)-2-methylamino-cyclohexan-1-one]has been used in both veterinary and human medicine. In this research, a new and efficient protocol has been developed for the synthesis of ketamine, by using hydroxy ketone intermediate.Synthesis of this drug has been done in five steps. At first, the cyclohexanone was made to react with 2-chlorophenyl magnesium bromide reagent followed by dehydration in the presence of an acidic ionic liquid, 1-methyl-3-[2-(dimethyl-4-sulfobutyl-ammonium) ethane] imidazolium hydrogen sulfate to obtain 1-(2-chlorophenyl)-cyclohexene. The oxidation of the synthesized alkene by potassium permanganate gave corresponding hydroxy ketone intermediate. The imination of this intermediate by methyl amine and finally the rearrangement of the obtained imine at elevated temperature resulted in the synthesis of ketamine. All of the intermediates and the product were characterized by 1H-NMR and IR spectroscopies. No need to use toxic bromine (which is used in most of the reported procedures for the synthesis of ketamine), high reaction yields and use of commercially available and safe materials and no need to use corrosive acids in the dehydration step are some of the advantages of this procedure over the common reported ones for the snthesis of ketamine. Graphic abstract: An efficient five-step protocol for the synthesis of ketamine was developed. Cyclohexanone reacted with 2-chlorophenyl magnesium bromide, followed by dehydration with acidic ionic liquid. Oxidation of the alkene gave corresponding hydroxy ketone intermediate.The imination of this intermediate and rearrangement of the obtained imine finally produced ketamine.[Figure not available: see fulltext.]
Process for (S)-Ketamine and (S)-Norketamine via Resolution Combined with Racemization
Gao, Shenghua,Gao, Xuezhi,Wu, Zenong,Li, Houyong,Yang, Zhezhou,Zhang, Fuli
supporting information, p. 8656 - 8664 (2020/07/21)
A concise, recyclable, and efficient process is presented for the preparation of (S)-ketamine (esketamine, (S)-1a) via classic resolution combined with the recycling of the undesired isomer. With commercially available ketone 2 as the starting material, this procedure features three steps including (1) an unique hydroxylation-ring expansion rearrangement, (2) mild amination via methanesulfonate, and (3) chiral separation using L-(+)-tartaric acid. The three simple steps are all performed in mild conditions and (S)-1a tartrate is obtained in 99.5percent ee without recrystallization. Subsequently, racemization of the unwanted (R)-1a remained in resolution mother liquor was performed in the presence of a Lewis acid in quantitative yield with >99.0percent chemical purity. This original and economical process afforded esketamine in 67.4percent (28.9percent without racemization) overall yield with two times recycling of the mother liquor without column purification. In addition, this procedure can also be applied to the preparation of (S)-norketamine, which is a safer potential antidepressant.
