19982-08-2

Basic information

• Product Name: Memantine
• Synonyms: AKOS BB-9600;MEMANTINE;AURORA KA-7643;TIMTEC-BB SBB002574;3,5-dimethyladamantan-1-amine HCl;1-Amino-3,5-dimethyladamantane;3,5-Dimethyl-1-aminoadamantane;3,5-DIMETHYL-1-AMINOADAMANTANE(MEMANTINE)
• CAS NO: 19982-08-2
• Molecular Formula: C₁₂H₂₁N
• Molecular Weight: 179.3
• EINECS: 1308068-626-2
• Product Categories: GASTERIL
• Mol File: 19982-08-2.mol

Chemical Properties

• Melting Point: 258 °C
• Boiling Point: 239.8 °C at 760 mmHg
• Flash Point: 92.3 °C
• Appearance: /
• Density: 1.046
• Vapor Pressure: 0.00667mmHg at 25°C
• Refractive Index: nD25 1.4941
• Storage Temp.: Store at RT
• Solubility: Chloroform (Slightly), DMSO (Slightly)
• PKA: 10.79±0.60(Predicted)
• CAS DataBase Reference: Memantine(CAS DataBase Reference)
• NIST Chemistry Reference: Memantine(19982-08-2)
• EPA Substance Registry System: Memantine(19982-08-2)

Safety Data

• Hazard Codes: Xi
• Safety Statements: 24/25
• Hazardous Substances Data: 19982-08-2(Hazardous Substances Data)

Usage

Uses

1. Used in Alzheimer's Disease Treatment:
Memantine is used as a therapeutic agent for the treatment of both mild and moderate-to-severe Alzheimer's disease, as well as possibly vascular dementia (multi-infarct dementia). Its method of action involves acting as an uncompetitive, low-affinity, open-channel blocker, entering the receptor-associated ion channel preferentially when it is excessively open. Importantly, its off-rate is relatively fast, preventing substantial accumulation in the channel and thus not interfering with normal synaptic transmission.
2. Used in Vascular Dementia (VaD) Treatment:
Memantine has been used in patients with VaD based on its experimental efficacy in animal models of ischemic lesions. It acts on potentially contributing factors such as neuronal depolarization, mitochondrial dysfunction, magnesium effects on NMDA receptors, and chronic glutamatergic overstimulation. Additionally, Memantine has shown positive effects on long-term potentiation and cognitive tests in standard animal models of impaired synaptic plasticity.
3. Used in Antiulcer Treatment:
Memantine is also used in the treatment of antiulcer, although the specific application reason is not detailed in the provided materials.

Originator

Akatinol,Merz,W. Germany,1983

Manufacturing Process

A mixture of 24 g of 1,3-dimethyladamantane and 80 ml of bromine was refluxed for 6 hours. The reaction product mixture was cooled, taken up in about 200 ml of chloroform, and poured onto ice. The excess bromine was removed by adding sodium hydrosulfite. The chloroform layer was separated from the aqueous layer, dried, concentrated in vacuo, and distilled at reduced pressure to yield 30.5 g of product having a boiling point of about 118°C at 5- 6 mm; nD25 = 1.5169-1.5182. The product was identified by nuclear magnetic resonance (NMR) and elemental analyses as 1-bromo-3,5- dimethyladamantane.A mixture of 20 g of 1-bromo-3,5-dimethyladamantane, 75 ml of acetonitrile, and 150 ml of concentrated sulfuric acid was allowed to react overnight at ambient room temperature. The red reaction product mixture was poured over crushed ice, and the white solid which precipitated was taken up in benzene and the benzene solution dried over sodium hydroxide pellets. The benzene solution was filtered from the drying agent and evaporated to dryness in vacuo to yield 18.2 g of product having a melting point of about 97°C and identified by infrared spectrum as 1-scetamido-3,5-dimethyladamantane.A mixture of 18 g of 1-acetamido-3,5-dimethyladamantane, 38 g of sodium hydroxide, and 300 ml of diethylene glycol was refluxed for a period of 6 hours. The reaction product mixture was cooled and poured onto about 2,000 ml of crushed ice. The basic solution thus obtained was extracted five times with 250 ml portions of benzene and the aqueous layer was discarded. The combined benzene extracts were dried over sodium hydroxide and the dried benzene solution concentrated in vacuo to give a crude oil weighing 14 g and having nD25 = 1.4941, A 4 g sample of the crude oil was dissolved in ether and the solution saturated with anhydrous hydrogen chloride. The solid which precipitated was filtered off and recrystallized from a mixture of alcohol and ether to yield product weighing 3.5 g and melting at 258°C.It was identified by analysis as 1-amino-3,5-dimethyladamantane hydrochloride.

Therapeutic Function

Spasmolytic

Biological Activity

An antagonist at the NMDA receptor, binding to the ion channel site. Used in the treatment of Parkinsonism.

Clinical Use

NMDA-receptor antagonist: Treatment of moderate to severe dementia in Alzheimer’s disease

Metabolism

Molecular weight (daltons) 215.8 % Protein binding 45 % Excreted unchanged in urine 48 (74% plus metabolites) Volume of distribution (L/kg) 10 Half-life - normal/ESRF (hrs) 60-100 / 117-1561

InChI:InChI=1/C12H21N.ClH/c1-10-3-9-4-11(2,6-10)8-12(13,5-9)7-10;/h9H,3-8,13H2,1-2H3;1H/t9-,10+,11-,12-;

Upstream product

• 19982-07-1 1-acetamido-3,5-dimethyladamantane 
• 41100-52-1 memantine hydrochloride 
• 947238-46-2 2-chloro-N-(3,5-dimethyl-adamantan-1-yl)-acetamide 
• 17356-08-0 thiourea 
• 941-37-7 3,5-dimethyl-1-bromoadamantane 
• 1204184-74-6 2-(3,5-dimethyladamantan-1-yl)isoindoline-1,3-dione 
• 351329-88-9 1-formamido-3,5-dimethyltricyclo[3.3.1.1^3,7]decane 
• 702-79-4 1,3-dimethyladamantane 
• 63534-29-2 1-azido-3,5-dimethyladamantane 
• 40430-57-7 3, 5-dimethyl-1-adamantyl methyl ketone 
• 707-37-9 3,5-dimethyladamantanol 
• 702-79-4 1,3-dimethyl-adamantane 
• 75-05-8 acetonitrile 

Downstream Products

• 100063-87-4 N'--N-<3,5-dimethyl-adamantyl-(1)>-harnstoff 
• 41100-52-1 memantine hydrochloride 
• 1185878-10-7 memantine-triflusal salt 
• 1388153-40-9 3,7-dihydro-N-(3,5-dimethyladamant-1-yl)-7-oxo-3-phenyl-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide 
• 710333-37-2 N-3,5-(dimethyladamantan-1-yl)-4-methylbenzenesulfonamide 

Relevant articles and documents

Synthesis, characterization, X-ray crystallography analysis and cell viability study of (η6-p-cymene)Ru(NH2R)X2 (X = Cl, Br) derivatives

Studies over the past few decades demonstrate the potential for metallodrugs as bioactive therapeutics. Here, we describe six new ruthenium(II) complexes with the general motif of (η6-p-cymene)Ru(NH2R)X2, where NH2R is either the influenza A antiviral drugs rimantadine or amantadine or the N-methyl-D-aspartate [NMDA] receptor antagonist, memantine and X = Cl or Br. All complexes were synthesized in high yield and purity and characterized by NMR spectroscopy and X-ray crystallography. Both the chlorine and bromine ruthenium(II) p-cymene complexes demonstrated cellular toxicity profiles similar to their respective free ligand, indicating that complexation to ruthenium(II) centers does not significantly increase toxicity of the bioactive ligand.

Synthesis, crystallographic studies, molecular modeling and in vitro biological studies of silver(I) complexes with aminoadamantane ligands

Silver(I) complexes with amantadine (atd) and memantine (mtn) were synthesized and characterized. Elemental, thermogravimetric and mass spectrometric analyses indicated a 1:2 metal/ligand ratio, with the molecular composition AgC20H34N2·NO3 for Ag–atd and AgC24H42N2·NO3·H2O for Ag–mtn. The crystal structures of the silver(I) complexes were determined by single crystal X-ray diffractometric studies and show the coordination of amantadine and memantine to the Ag(I) ion by the nitrogen atom of the NH2 group. The spectral analysis by infrared and 1H, 13C and {15N,1H} nuclear magnetic resonance (NMR) spectroscopies confirmed the coordination sites of the ligands to the silver ions. Computational studies revealed modes of vibration and bond lengths similar to those found experimentally. The in vitro antibacterial activity assays showed that amantadine is not active over the tested strains while memantine showed a low activity against Staphylococcus aureus and Pseudomonas aeruginosa. On the other hand, the complexes had a pronounced antibacterial activity over the same strains with minimum inhibitory concentration (MIC) values in the micromolar range. Biophysical assays based on fluorescence spectroscopy indicated that the silver(I) complexes interact weakly with bovine serum albumin, while agarose gel electrophoresis and competitive binding experiments revealed that the compounds interact with DNA by non-covalent interactions.

Green preparation method of memantine

The method comprises the following steps: (1) mixing 1 - chlorine -3 and 5 - dimethyl adamantane with acetamide to obtain 1 -acetylamino -3 and 5 -dimethyladamantane. (2) The 1 -acetylamino -3, 5 -dimethyladamantane was deacetylated in a hot-water system to obtain a memantine. The preparation method provided by the invention is simple to operate. The method is safe, environment-friendly, high in yield and purity, cost-saving, low in production cost and beneficial to industrial production.

Memantine hydrochloride synthesis method

The invention provides a memantine hydrochloride synthesis method, and belongs to the technical field of medicine synthesis. The preparation method comprises the following steps: carrying out a substitution reaction on 1-bromo-3,5-dimethyladamantane and acetamide to obtain 1-acetamido-3,5-dimethyladamantane, mixing the 1-acetamido-3,5-dimethyladamantane, an alcohol and an alkali, carrying out an alcoholysis reaction to obtain 1-amino-3,5-dimethyladamantane, and finally carrying out an acidification reaction on the 1-amino-3,5-dimethyladamantane and hydrochloric acid to obtain memantine hydrochloride. According to the method of the invention, 1-bromo-3,5-dimethyl adamantane and acetamide are used as the starting raw materials, so the sources of the raw materials are wide, the use of acetonitrile is avoided, and no pollution is caused to the human body and the environment; the use of catalysts is avoided in the whole reaction process, the reaction product is easy to separate, and the yield of the obtained memantine hydrochloride is high; and the method is mild in reaction condition and suitable for industrial production.

Cerium-Catalyzed C-H Functionalizations of Alkanes Utilizing Alcohols as Hydrogen Atom Transfer Agents

Modern photoredox catalysis has traditionally relied upon metal-to-ligand charge-transfer (MLCT) excitation of metal polypyridyl complexes for the utilization of light energy for the activation of organic substrates. Here, we demonstrate the catalytic application of ligand-to-metal charge-transfer (LMCT) excitation of cerium alkoxide complexes for the facile activation of alkanes utilizing abundant and inexpensive cerium trichloride as the catalyst. As demonstrated by cerium-catalyzed C-H amination and the alkylation of hydrocarbons, this reaction manifold has enabled the facile use of abundant alcohols as practical and selective hydrogen atom transfer (HAT) agents via the direct access of energetically challenging alkoxy radicals. Furthermore, the LMCT excitation event has been investigated through a series of spectroscopic experiments, revealing a rapid bond homolysis process and an effective production of alkoxy radicals, collectively ruling out the LMCT/homolysis event as the rate-determining step of this C-H functionalization.

Synthesis, molecular docking studies, and antimicrobial evaluation of new structurally diverse ureas

A series of new urea derivatives (3a-p) have been synthesized from readily available isocyanates and amines in good to high yields. All synthesized compounds were fully characterized using 1H NMR, 13C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (3n) was confirmed by single-crystal X-ray diffraction. Furthermore, all compounds were evaluated for antimicrobial activity against five bacteria and two fungi. Last but not the least, molecular docking studies with Candida albicans dihydropteroate synthetase were performed and the results are presented herein.

Deacetylative Amination of Acetyl Arenes and Alkanes with C-C Bond Cleavage

The Br?nsted acid-catalyzed synthesis of primary amines from acetyl arenes and alkanes with C-C bond cleavage is described. Although the conversion from an acetyl group to amine has traditionally required multiple steps, the method described herein, which uses an oxime reagent as an amino group source, achieves the transformation directly via domino transoximation/Beckmann rearrangement/Pinner reaction. The method was also applied to the synthesis of γ-aminobutyric acids, such as baclophen and rolipram.

CRYSTAL OF 1-AMINO-3,5-DIMETHYL ADAMANTANE HYDROCHLORIDE

PROBLEM TO BE SOLVED: To provide a crystals of 1-amino-3,5-dimethyl adamantane hydrochloride that has excellent fluidity. SOLUTION: Provided is a crystal of 1-amino-3,5-dimethyl adamantane hydrochloride having a crystal aspect ratio of 1.0 to 1.5. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT

A hydrochloric acid just preparation method

The invention discloses a method for preparing memantine hydrochloride. The method is characterized in that the method provided by the invention uses 1-bromo-3,5-dimethyladamantane (represented by a general formula IV in the description) as a starting material which is subjected to an amination reaction with acetamine to obtain a key intermediate 1-actamido-3,5-dimethyladmantane (represented by a general formula III in the description); the compound represented by the general formula III is subjected to alcoholysis in a mixture system of inorganic base and n-butyl alcohol for deacetylated to obtain memantine; memantine is treated using hydrochloric acid in a ketone solvent to obtain memantine hydrochloride. The method provided by the invention overcomes deficiencies in the prior art and has the advantages that the raw materials are simple and readily available, the reaction steps are simple and short, and the operations are convenient and fast, therefore, the method is suitable for industrial production.

A hydrochloric acid just preparation method

The present invention discloses a memantine hydrochloride preparation method, especially a method for synthesizing memantine hydrochloride by adopting 1-bromo-3,5-dimethyl adamantane as a starting raw material. The memantine hydrochloride preparation method is characterized in that the reaction process from the starting raw material to the final product is shortened into the one-step reaction, the 1-bromo-3,5-dimethyl adamantane is adopted as the starting raw material, the 1-bromo-3,5-dimethyl adamantine and ammonium acetate are subjected to direct amination, and the adjustment is performed to obtain the memantine hydrochloride. Compared with the memantine hydrochloride preparation method in the prior art, the memantine hydrochloride preparation method of the present invention has the following advantages that: the memantine hydrochloride prepared by the preparation method of the present invention has characteristics of stable quality, high purity, the total impurity of less than 0.3%, the single impurity of less than 0.05% and the yield of 88-90%, and the preparation method has characteristics of less reaction steps, simple operation, mild reaction conditions, and easy industrial production achieving.