6740-88-1

Usage

InChI:InChI=1/C13H16ClNO/c1-15-13(9-5-4-8-12(13)16)10-6-2-3-7-11(10)14/h2-3,6-7,15H,4-5,8-9H2,1H3/p+1/t13-/m1/s1

Upstream product

• 2079878-75-2 2-(2-chlorophenyl)-2-nitrocyclohexan-1-one 
• 50-00-0 formaldehyd 
• 35211-10-0 norketamine 
• 91393-49-6 2-amino-2-(2-chlorophenyl)cyclohexan-1-one 
• 33795-24-3 (+)-Ketamine hydrochloride 
• 74-89-5 methylamine 
• 3900-89-8 2-Chlorobenzeneboronic acid 
• 17465-36-0 2'-chloro-2,3,4,5-tetrahydro-1,1'-biphenyl 
• 6740-86-9 (1-Bromocyclopentyl)(2-chlorophenyl)methanone 
• 445249-11-6 3-bromo-2-methoxycyclohex-2-en-1-one 
• 90717-17-2 (±)-(2-chlorophenyl)(1-hydroxycyclopentyl)methanone 
• 6740-87-0 1-((2-chlorophenyl)(methylimino)methyl)cyclopentan-1-ol 
• 873-32-5 2-Chlorobenzonitrile 
• 6740-85-8 (2-chlorophenyl)(cyclopentyl)methanone 

Downstream Products

• 91003-15-5 3-(o-Chlorophenyl)-2-hydroxycyclohex-2-enone 
• 57683-62-2 6-amino-6-(2-chlorophenyl)-2-cyclohexen-1-one 
• 35211-10-0 norketamine 
• 120199-64-6 2-Hydroxy-Norketamine 
• 79499-53-9 2,2-Dibromo-6-(2-chlorophenyl)-6-(methylamino)cyclohexanone 
• 79548-69-9 6-Bromo-2-(2-chlorophenyl)-2-(Methylamino)cyclohexanone hydrobromide 
• 79548-71-3 6-Bromo-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone 
• 79548-68-8 6-Bromo-2-(2-chlorophenyl)-2-(Methylamino)cyclohexanone 
• 91003-09-7 N-Benzoylketamine 
• 91003-12-2 2-(o-Chlorophenyl)-2-<(benzyloxycarbonyl)methylamino>cyclohexanone 
• 91003-19-9 2-(o-Chlorophenyl)-2-<(methoxycarbonyl)methylamino>cyclohexanone 
• 50-00-0 formaldehyd 
• 33795-24-3 (+)-Ketamine hydrochloride 
• 33643-47-9 (-)-Ketamine hydrochloride 

Relevant academic research and scientific papers

LONG-ACTING INJECTABLE FORMULATIONS OF KETAMINE PAMOATE SALTS

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.

Preparation method of ketamine and synthesis method of intermediate compound

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

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

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.

Synthesis of ketamine from a nontoxic procedure: a new and efficient route

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

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.

Enantioselective Syntheses of (S)-Ketamine and (S)-Norketamine

An efficient asymmetric synthesis of (S)-ketamine (esketamine) based on catalytic enantioselective transfer hydrogenation of cyclic enone and [3,3]-sigmatropic rearrangement of allylic cyanate to isocyanate is described. The catalytic asymmetric route afforded esketamine (99.9% ee) in 50% overall yield over four steps and forms the basis for the future development of the drug substance. Furthermore, the route was applicable to the synthesis of (S)-norketamine via simple hydrolysis of isocyanate penultimate.

IMPROVEMENTS IN OR RELATING TO ORGANIC MATERIAL

The invention provides a method for synthesizing a compound of formula (I) wherein each R independently represents an optionally substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, cyano, sulfo or sulfhydryl group, in ortho, meta or para position to the cycloalkylamine moiety; R1 and R2 each independently represents a hydrogen atom, a lower alkyl group or a cycloalkyl group; R3 represents a hydrogen group, substituted aryl, heteroaryl, alkyl, perfluoroalkyl, cycloalkyl, alkoxy, aryloxy group; Y represents an oxygen atom, a sulfur atom, a NH group, a NR4 group or a CH2 group; R4 represents a hydrogen atom or an alkyl, aryl or a heteroaryl group; and n and m each independently represents an integer from 1 to 5; or a pharmaceutically acceptable salt thereof; or a precursor thereof; wherein the method comprises one or more of the following steps: (a) reacting a compound of formula (II): (II) wherein R, R3, Y, n and m are as defined above in relation to the compound of formula (I) with an oxygenating agent, a first additive and a second additive in a solvent in a fluidic network or in a batch process under thermal and/or photochemical conditions to form a compound of formula (III): (III) wherein R, R3, Y, n and m are as defined above in relation to the compound of formula (I), (b) reacting a compound of formula (III) with a nitrogen containing nucleophile in the presence of a third additive and/or a solvent in the fluidic network or in a batch process under thermal conditions to form a compound of formula (IV): (IV) wherein R, R1, R2, R3, Y, n and m are as defined above in relation to the compound of formula (I); and/or (c) reacting a compound of formula (IV) in a fluidic network or in a batch process, optionally in the presence of a fourth 20 additive, under thermal conditions to form a compound of formula (I); wherein one or more of steps (a), (b) and/or (c) is carried out in a fluidic network that comprises micro- and/or meso-channels having an internal dimension of from 100 μm to 2000 μm.

COMPOSITIONS AND METHODS FOR THE TREATMENT OF NEUROLOGICAL DISEASES

The invention relates to the compounds or its pharmaceutical acceptable polymorphs, solvates, enantiomers, stereoisomers and hydrates thereof. The pharmaceutical compositions comprising an effective amount of compounds of formula I, formula II and formula III and the methods for the treatment of neurological diseases may be formulated for oral, buccal, rectal, topical, transdermal, transmucosal, lozenge, spray, intravenous, oral solution, nasal spray, oral solution, suspension, oral spray, buccal mucosal layer tablet, parenteral administration, syrup, or injection. Such compositions may be used to treatment of neurological diseases.

Expedient preparation of active pharmaceutical ingredient ketamine under sustainable continuous flow conditions

A robust three-step continuous flow procedure is presented for the efficient and sustainable preparation of active pharmaceutical ingredient ketamine. The procedure relies on the main assets of continuous flow processing, starts from commercially available chemicals, utilizes low toxicity reagents and a FDA class 3 solvent under intensified conditions. The procedure features a unique hydroxylation step with molecular oxygen, a fast imination relying on triisopropyl borate and a thermolysis employing Montmorillonite K10 as a heterogeneous catalyst, all three steps being performed in ethanol. The three individual steps can be run independently or can be concatenated, thus providing a compact yet efficient setup for the production of ketamine. The scalability of the critical hydroxylation step was assessed in a commercial pilot continuous flow reactor. The process can also be adapted for the preparation of ketamine analogs. A thorough computational study on the backbone rearrangement of the cyclopentylphenylketone scaffold under thermal stress rationalizes the experimental selectivity and the various experimental observations reported herein.