cas 41100-52-1, Memantine HCl | Articles data

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Preparation method of 3,5-dimethyladamantanamine hydrochloride
The invention discloses a preparation method of 3,5-dimethyl adamantanamine hydrochloride. The method comprises the following steps: adding 1-nitro-3,5-dimethyladamantane into a first solvent, and carrying out hydrogenation reaction in the presence of a catalyst; desolventizing the hydride material, adding water, and distilling with water vapor; extracting the distillate with a second solvent, adding hydrochloric acid, performing azeotropic dehydration, and performing crystallization separation to prepare the 3,5-dimethyladamantanamine hydrochloride. The method has the advantages of cheap and easily available raw materials, mild reaction conditions, high yield, good product quality and easy realization of industrial production.
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Paragraph 0032-0047

(2021/12/07)

Green and efficient preparation method of medicament for treating Alzheimer's disease
The invention discloses a green and efficient preparation method of a medicament for treating Alzheimer's disease, which comprises the following steps of reacting 1-bromo-3, 5-dimethyl adamantane serving as a raw material under the action of acetonitrile, pyridine p-toluenesulfonate and acid to synthesize 1-acetamido-3, 5-dimethyl adamantane, then carrying out reflux reaction hydrolysis in organicweak acid to obtain 1-amino-3, 5-dimethyl adamantane, and finally acidifying into salt by using hydrochloric acid to obtain a product with the purity of more than 99%. On one hand, by adding pyridinep-toluenesulfonate, the operation risk caused by using a large amount of concentrated sulfuric acid is avoided, the reaction time is shortened, and the reaction temperature is reduced; on the other hand, 1-acetamido-3, 5-dimethyl adamantane is refined and concentrated in alcohol water and then subjected to amide hydrolysis in organic weak acid, the reaction proceeding degree is improved, the reaction temperature and the high requirement of high-temperature strong-alkali reaction for equipment are reduced, the organic weak acid can be recycled and reused, the method is more environmentally friendly, the production cost is reduced, - the reaction yield is high and the product purity is good.
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Paragraph 0017-0055

(2021/02/10)

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.
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(2020/03/09)

Memantine hydrochloride impurity compound and preparation method thereof
The invention discloses a preparation method of a memantine hydrochloride impurity compound 1-nitro-7-hydroxy-3,5-dimethyl adamantane. According to the preparation method, 1-bromo-3,5-dimethyl adamantane is taken as a raw material and carries out a substitution reaction with acetamide in a molten state, then hydrolysis and salt forming happen in an alkaline environment, and finally the target product is prepared after hydroxylation and oxidation. The impurity compound is used as a reference substance for memantine hydrochloride quality control.
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(2020/06/20)

PROCESS FOR PREPARATION OF MEMANTINE
The present invention provides an improved process of manufacturing 1-Bromo-3,5-dimethyladamantane compound of formula-IV starting from 1,3-dimethyladamantane that avoids use of liquid bromine and minimizes the use of hazardous chemicals. The present invention also provides use of 1-Bromo-3,5-dimethyladamantane prepared by the process of present invention in the process of producing Memantine hydrochloride and pharmaceutical compositions thereof.
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(2020/05/19)

An Improved Synthesis of Memantine Hydrochloride
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Ba, Ngoc Minh Ho,Chau Phan, Dinh,Duong Vu, Binh,Tran, Hung Van
(2020/09/18)

Preparation method of memantine hydrochloride (by machine translation)
The preparation method of the memantine hydrochloride, comprises the following steps,1 - bromo - 333355-dimethyladamantane, used as a hydrolysis reagent, to hydrolyze the formamide group to obtain a finished product of memantine hydrochloride . The method disclosed by the invention is relatively mild in preparation conditions and low in cost, obtained by hydrolysis of the amino substituent, by using formamide as a hydrolysis reagent . The method, further comprises the following steps: preparing a finished product of, memantine hydrochloride by using, a sodium hydroxide solution as a, hydrolysis reagent. (by machine translation)
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Page/Page column 4-5

(2020/05/08)

Preparation method of medicine for treating neurological function diseases
The invention discloses a preparation method of a medicine for treating neurological function diseases, which comprises the following steps: 1) adding 1-bromo-3,5-dimethyl adamantane, acetonitrile, acatalyst 1 and a catalyst 2 into a reaction kettle, stirring to react, adding a certain amount of water into the reaction solution, cooling to precipitate a solid, adding the solid into a certain proportion of an alcohol water solution, and carrying out hot melting and cold precipitation to obtain 1-acetamido-1,3-dimethyl adamantane; and (2) carrying out high-temperature reaction on 1-acetamido-1,3-dimethyl adamantane and sodium hydroxide in ethylene glycol, adding a certain amount of purified water, extracting by adopting dichloromethane, concentrating under reduced pressure, adding an ethylacetate hydrochloride solution into the concentrated solution, cooling to allow crystal growing, carrying out suction filtration, and drying to obtain memantine hydrochloride. According to the method,the catalyst 1 and the catalyst 2 are used as reaction catalysts, so that the operation risk caused by the use of concentrated sulfuric acid is avoided, the reaction time is shortened, and the side reaction is reduced. The post-treatment is simple, the reaction yield is high, and the product purity is good.
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Paragraph 0022; 0025-0026; 0029-0030; 0033-0034; 0037-0038

(2020/11/23)

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.
An, Qing,Chen, Yuegang,Liu, Weimin,Pan, Hui,Wang, Xin,Wang, Ziyu,Zhang, Kaining,Zuo, Zhiwei
supporting information
p. 6216 - 6226
(2020/04/27)

Intermolecular Radical C(sp3)?H Amination under Iodine Catalysis
The direct amination of aliphatic C?H bonds has remained one of the most tantalizing transformations in organic chemistry. Herein, we report on a unique catalyst system, which enables the elusive intermolecular C(sp3)?H amination. This practical synthetic strategy provides access to aminated building blocks and fosters innovative multiple C?H amination within a new approach to aminated heterocycles. The synthetic utility is demonstrated by the synthesis of four relevant pharmaceuticals.
Bosnidou, Alexandra E.,Mu?iz, Kilian
supporting information
p. 7485 - 7489
(2019/04/30)

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.
Hyodo, Kengo,Hasegawa, Genna,Maki, Hiroya,Uchida, Kingo
p. 2818 - 2822
(2019/04/25)

Method for preparing memantine hydrochloride
The invention belongs to the field of pharmaceutical synthesis and particularly relates to a method for preparing memantine hydrochloride. The method includes that 1-minus chlorine-3,5-dimethyl is taken as a raw material which is amidated via methanamide and hydrolyzed via hydrochloric acid to obtain a target product directly with a one-step method, wherein the yielding rate can be up to 80%, andthe product purity excesses 99.0%. Compared with a traditional synthesis process, the novel process is simple in synthesis steps, product cost is greatly reduced, little pollution is caused to the environment, and environmental problems caused by the production of the memantine hydrochloride are greatly alleviated.
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Paragraph 0026-0035

(2019/07/04)

Improvement method for synthesis process of memantine hydrochloride
The invention discloses an improvement method for a synthesis process of memantine hydrochloride; with 1,3-dimethyl adamantane as a raw material, 3,5-dimethyl-1-adamantanol is obtained through a bromination reaction and a hydrolysis reaction; 3,5-dimethyl-1-adamantanol is subjected to a chlorination reaction to obtain 1-chloro-3,5-dimethyl adamantane; and 1-chloro-3,5-dimethyl adamantane is subjected to an ammoniation reaction, acid hydrolysis and salt formation, and the target product of methamine hydrochloride is produced, wherein in the bromination reaction, the reaction molar ratio of 1,3-dimethyl adamantane and bromine is 1:1.1, the reaction is performed in dichloroethane, and after the hydrolysis reaction, an organic phase is separated and washed to remove bromine and washed and dried, and an obtained solution is directly used for a next reaction. The improvement method provided by the invention can improve the yield, increase reaction safety and reduce waste and waste water.
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(2018/07/30)

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.
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(2018/04/02)

Process for preparing high-purity hydrochloric acid method of memantine
The invention discloses a method for preparing highly pure memantine hydrochloride. 1-Amino-3,5-dimethyladamantane (memantine) with the purity of 96% is adopted as an initial raw material, and the purity of the hydrochloride of the initial material cannot reach raw medicine standards, so the highly pure memantine hydrochloride can be obtained through a technological scheme. The technologic scheme is characterized in that the method comprises the following steps: dissolving memantine in a dichloromethane and ethanol mixed solution with a certain proportioning concentration, adding water, adjusting the pH value, extracting, adding dichloromethane, adding an alkali to adjust the pH value, and extracting; carrying out rotary reduced pressure evaporation on the above obtained organic phase to dryness in order to obtain a concentrate; dissolving the concentrate in a proper amount of acetonitrile, adding concentrated hydrochloric acid, and adjusting the pH value to 1-3 in order to obtain a large amount of a solid; carrying out pumping filtration, and leaching the obtained filter cake with cold acetonitrile; and re-crystallizing with 95% ethanol to obtain the highly pure memantine hydrochloride. In the preparation process, dichloromethane, ethanol, water, acetonitrile and other solvents are selected by post-treatmetn, so the method has the advantages of small toxicity, small pollution to environment, simple and feasible operation, and convenient industrial large-scale production. The purity of the memantine hydrochloride can reach 99.99%, and is higher than memantine hydrochloride prepared through traditional preparation methods.
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Page/Page column 4-6

(2018/10/11)

METHOD FOR PRODUCING 1-AMINO-3,5-DIMETHYLADAMANTANE HYDROCHLORIDE
PROBLEM TO BE SOLVED: To provide a new method for producing 1-amino-3,5-dimethyladamantane hydrochloride. SOLUTION: A method for producing 1-amino-3,5-dimethyladamantane hydrochloride has the steps for making a compound represented by formula (1), a compound represented by formula (2) and organic acid react with each other, to obtain salt of 1-amino-3,5-dimethyl adamantane and the organic acid, and converting the salt into 1-amino-3,5-dimethyladamantane hydrochloride represented by formula (4) (where X is a leaving group, and R is a hydrogen atom, a hydroxy group, an alkyl group having 1 to 4 carbon atoms or an alkoxy group having 1 to 4 carbon atoms). SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0046

(2017/07/23)

METHOD FOR MANUFACTURING HIGHLY-PURE MEMANTINE HYDROCHLORIDE
PROBLEM TO BE SOLVED: To provide a highly efficient, inexpensive and safe method for manufacturing memantine hydrochloride of high purity. SOLUTION: By reacting 1-halogeno-3,5-dimethyl adamantane and urea or thiourea in a non-aprotic polar solvent, a solution of 1-carbamide-3,5-dimethyl adamantane or 1-thiocarbamide-3,5-dimethyl adamantane is obtained. By adding a base or an acid, the obtained solution is decomposed into memantine or its salt. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0035

(2017/06/20)

Convenient Synthesis of Memantine Hydrochloride
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Ivleva, Elena A.,Klimochkin, Yuri N.
p. 155 - 162
(2017/04/26)

METHOD FOR PRODUCING 1-AMINO-3,5-DIMETHYL ADAMANTANE HYDROCHLORIDE
PROBLEM TO BE SOLVED: To provide a novel method for producing 1-amino-3,5-dimethyl adamantane hydrochloride. SOLUTION: The production method comprises: a step of producing a compound (2) by reacting 1,3-dimethyl adamantane with compound (1) in a reaction solution, and then compound (3) is added to the reaction solution containing compound (2) to produce compound (4); a step of converting compound (4) to compound (5); and a step of bringing compound (5) into contact with hydrogen chloride or a solution thereof to convert to 1-amino-3,5-dimethyl adamantane hydrochloride (6). [X is a halogen atom; R is H, a hydroxy group, an optionally substituted C1 to 4 alkyl group, an optionally substituted C1 to 4 alkoxy group or an optionally substituted C7 to 13 aralkyl-oxy group.]. SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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(2017/07/23)

Preparation method of memantine hydrochloride
The invention relates to a preparation method of memantine hydrochloride. According to the preparation method, crude 1-acetylamino-3,5-dimethyladamantane is prepared via direction reaction of a system composed of 1,3-dimethyladamantane, acetonitrile, and concentrated sulfuric acid; the crude 1-acetylamino-3,5-dimethyladamantane is subjected to hydrolysis without purifying directly; ethanediol is taken as a solvent, and crude memantine is obtained via hydrolysis under alkaline conditions; crude memantine is extracted with hydrocarbon solvents such as n-heptane; concentrated hydrochloric acid or an organic solution of hydrochloric acid is added into an obtained extracted solution directly so as to obtain a crude memantine hydrochloride solid; and recrystallization is carried out with an alcohol-ethyl acetate system so as to obtain refined memantine hydrochloride. Operation of the preparation method is simple; the preparation method is simplified; yield is high; production cost is low; and the preparation method is suitable for industrialized production.
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(2017/10/12)

Preparation method for memantine hydrochloride
The invention provides a preparation method for memantine hydrochloride. The method comprises the following steps: reducing 1-nitro-3,5-dimethyl adamantane in the presence of a weak acid by taking iron powder as a reducer, so as to obtain memantine; and acidifying the obtained memantine into a salt, thereby obtaining the memantine hydrochloride. The preparation method provided by the invention is simple and is applicable to the industrial-scale production of the memantine hydrochloride; the iron powder serves as the reducer, so that the risk of explosion resulted from the catalytic hydrogenated reduction of nitro by Pd/C is avoided; and meanwhile, process operating steps are simplified, and the production capacity is improved, so that the yield of the memantine hydrochloride reaches 83% or more, and the product purity is 99.8% or more.
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Paragraph 0038-0040

(2017/05/26)

A hydrochloric acid just preparation method
The present invention discloses a memantine hydrochloride preparation method, which is characterized by comprising: A, adopting formic acid as a solvent, and carrying out a reaction of carbamate and a compound II for 0.25-4 h at a temperature of 50-150 DEG C to obtain a mixture a; and B, evaporating the mixture a to remove the formic acid, adding hydrochloric acid, carrying out hydrolysis for 0.5-10 h at a temperature of 40-110 DEG C, carrying out cooling crystallization at a temperature of -5-30 DEG C, and filtering to obtain the memantine hydrochloride, wherein the carbamate is as the follow, the compound II is 1-bromo-3,4-dimethyl adamantane, and R is methyl or ethyl. According to the present invention, the carbamate and the compound II are adopted as the raw materials without use of toxic, harmful and hazardous raw materials; the carbamate is adopted as the amino source in the reaction, such that the reaction can be performed in the rapid, homogeneous-phase and stable manner; and characteristics of simple reaction condition, low reaction temperature, short reaction time, high final product collection rate and low cost are provided.
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Paragraph 0048; 0049; 0050

(2017/02/02)

A Namenda preparation method
The invention relates to a preparation method of memantine hydrochloride, which comprises the following steps: reacting 1-bromo-3,5-dimethyladamantane with acetamide to obtain 1-acetamino-3,5-dimethyladamantane, reacting the 1-acetamino-3,5-dimethyladamantane with sodium methoxide and ethylene glycol, extracting, acidifying with hydrochloric acid to generate the target compound memantine hydrochloride, and recrystallizing the memantine hydrochloride crude product to obtain the memantine hydrochloride final product. By using the 1-acetamino-3,5-dimethyladamantane as the raw material, the method reduces the consumption of toxic, harmful and dangerous raw materials, has the advantages of high yield of the final product and lower cost, and is suitable for industrial production.
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Paragraph 0051; 0052

(2017/01/02)

PRODUCTION METHOD OF 1-AMINO-3,5-DIMETHYLADAMANTANE HYDROCHLORIDE
PROBLEM TO BE SOLVED: To provide a production method of 1-amino-3,5-dimethyladamantane hydrochloride with a high yield, of which the amount of predetermined impurities (trimethyl analog and monomethyl analog) is reduced, which has high purity, and which can be used for pharmaceutical application as it is. SOLUTION: 1-amino-3,5-dimethyladamantane hydrochloride is crystallized from a mixed solution of: a protic solvent such as an organic acid, an alcohol; an aprotic solvent such as ketones, esters, nitriles; and water. SELECTED DRAWING: None COPYRIGHT: (C)2016,JPO&INPIT
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Paragraph 0044

(2017/05/17)

AN IMPROVED PROCESS FOR THE PREPARATION OF MEMANTINE HYDROCHLORIDE
The present invention relates to an improved process for the preparation of memantine hydrochloride. Memantine hydrochloride is used in the treatment of Alzheimer's and Parkinson's disease.
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Page/Page column 10

(2014/03/21)

Synthesis and IR/MS study of 3,5-dimethyladamantanamine hydrochloride salt
This paper studied the synthesis of memantine hydrochloride characteristics by optimizing the synthetic route in the bromination of acid hydrolysis under the conditions of acetonitrile and the final salt formation reaction, so that memantine hydrochloride in an overall yield of the products from the 67.3 % reported in the literature increased to 81.5 %. Compared to 1,3-dimethyl adamantane and 3,5-dimethyladamantanamine, the infrared spectra showed the characteristic absorptions of 3,5-dimethyl-adamantanamine hydrochloride. Especially by the use of ESI method Spray ionization mass spectrometry analysis of fragments of memantine hydrochloride mass characteristics of ammonia compounds. By IR and MS studies to determine the spectrum of memantine hydrochloride microscopic molecular structure of ammonia.
Ren, Huixue,Ying, Hanjie,Ouyang, Pingkai,Lin, Jimao,Jing, Liu
p. 5107 - 5110
(2012/10/08)

PROCESS FOR THE PREPARATION OF 1-BROMO-3,5-DIMETHYL ADAMANTANE
The present invention relates to an improved process for the preparation of 1-bromo-3,5-dimethyl adamantane of formula (III), which is an useful intermediate for synthesis of 1-amino-3,5-dimethyl adamantane of formula (I) or pharmaceutically acceptable salt thereof.
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Page/Page column 3

(2012/01/03)

PROCESS FOR THE PREPARATION OF MEMANTINE HYDROCHLORIDE
The present invention provides an improved process for the preparation of 1-bromo-3,5-dimethyladamantane. The present invention also provides a process for preparing free flowing solid of 1-acetamido-3,5-dimethyladamantane. The present invention further provides a process for the preparation of memantine hydrochloride substantially free of 1-amino-3,5,7-trimethyladamantane hydrochloride and/or 1-amino-3-methyladamantane hydrochloride impurity.
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Page/Page column 8-9

(2011/10/31)

METHOD FOR PRODUCING MEMANTINE
Method for producing 1-amino-3,5-dimethyladamantane or a salt thereof, comprising: (i) heating 1-formamido-3,5-dimethyladamantane with a base in a protic solvent.
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Page/Page column 22-23

(2010/08/05)

PROCESS FOR MANUFACTURING ADAMANTANE DERIVATIVES WITH HIGH YIELD
The present invention pertains to process for the amidation of a substituted 1-bromo-adamantane comprising a step (0) of reacting a substituted adamantane with an excess of bromine to obtain a 1-bromo-adamantane and a step (i) of reacting said substituted 1-bromo-adamantane with an amide, wherein the substituted 1-bromo-adamantane is used in the form of a mixture comprising bromine as obtained in step (0), wherein in step (0) a bromine: substituted adamantane molar ratio of from [2.5:1] to less than [5:1] is employed.
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Page/Page column 16-17

(2010/04/03)

A PROCESS FOR PREPARING MEMANTINE
The present invention relates to a process for preparing memantine, or a pharmaceutically acceptable salt thereof (e.g., memantine hydrochloride), which is substantially free of impurities.
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Page/Page column 20-21; 22

(2010/08/08)

AN IMPROVED PROCESS FOR THE PREPARATION OF 1-BROMO-3,5-DIMETHYL ADAMANTANE
The present invention relates to an improved process for the preparation of 1-bromo-3,5-dimethyl adamantane of formula (III), which is an useful intermediate for synthesis of 1-amino-3,5-dimethyl adamantane of formula (I) or pharmaceutically acceptable salt thereof.
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Page/Page column 7

(2010/07/02)

PROCESS FOR THE PREPARATION OF MEMANTINE AND ITS SALTS AND INTERMEDIATE FOR USE THEREIN
The present invention provides 2-(3,5-dimethyl-adamantan-1-yl)-isoindole-1,3-dione of formula II, which is useful as an intermediate in the preparation of memantine and its salts. The present invention also provides a process for preparing 2-(3,5-dimethyl-adamantan-1- yl)-isoindole-1,3-dione and a process for preparing memantine or a salt thereof using 2- (3,5-dimethyl-adamantan-1 -yl)-isoindole-1,3-dione.
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Page/Page column 13

(2010/04/03)

PROCESS FOR PREPARING MEMANTINE HYDROCHLORIDE SUBSTANTIALLY FREE OF !MPURITIES
A process for preparing memantine hydrochloride free from impurities comprises (a) reacting 1,3-dimethyladarnantane with acetontitrile and sulphuric acid to produce 1- acetamido-3,5-dimethyl adamantane; (b) treating l-acetamido-3,5-dimethyl adamantane with base in the presence of solvent to produce memantine; (c) reacting memantine with alcoholic HCl in the presence of solvents to produce memantine hydrochloride; and purification of memantine hydrochloride using aliphatic solvents.
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(2010/01/12)

IMPROVED PROCESS FOR MEMANTINE HYDROCHLORIDE
The present invention provides an improved eco-friendly process for the preparation of memantine hydrochloride compound of formula (1). The present invention also provides one-pot process for the preparation of memantine hydrochloride compound of fomula (1) from 1,3 -dimethyl adamantane without isolating any intermediates.
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Page/Page column 13-16

(2009/06/27)

Method for Producing 1-Formamido-3,5-Dimethyladamantane
The invention relates to a method for producing 1-formamido-3,5-dimethyladamantane in only two reaction steps by direct formamide formation of 1,3-dimethyladamantane, the 1,3-dimethyladamantane being reacted with formamide in concentrated acids.
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Page/Page column 2

(2009/12/23)

Process for the manufacture of memantine and intermediate product
The present invention relates to a process for manufacturing N-Formyl-1-amino-3,5-dimethyladamantane, an intermediate product in the overall process of producing 1-Amino-3,5-dimethyladamantane hydrochloride (Memantine). Therein, the process comprises the following steps: (a) reacting 1,3-dimethyladamantane with an acid mixture comprising concentrated sulfuric acid and concentrated nitric acid, wherein 1 to 6 volume parts of sulfuric acid are used per weight part of 1,3-dimethyladamantane; (b) reacting the solution from step (a) with an amount of formamide varying from 1 to 5 molar equivalents per mole of deprotonated 1,3-dimethyladamantane from step (a) to obtain N-Formyl-1-amino-3,5-dimethyladamantane. In step (b), the molar ratio of total acid, i.e. the molar amount of sulfuric acid and the molar amount of nitric acid taken together versus the molar amount of formamide is at least 1.5 and that the temperature is at least 50°C. The present invention also relates to the overall process of manufacturing Memantine from 1,3-dimethyladamantane by means of hydrolyzing the intermediate NFORM.
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Page/Page column 6

(2009/10/01)

METHODS OF TREATING CNS DISORDERS
The present invention relates to methods of treating various CNS disorders, e.g., mania, bipolar disorder and schizophrenia, by administering NMDA receptor antagonists, alone or in combination with dopamine receptor antagonists.
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(2009/12/02)

N-tosyloxycarbamates as reagents in rhodium-catalyzed C-H amination reactions
Metal nitrenes for use in C-H insertion reactions were obtained from N-tosyloxycarbamates in the presence of an inorganic base and a rhodium(II) dimer complex catalyst. The C-H amination reaction proceeds smoothly, and the potassium tosylate that forms as a byproduct is easily removed by filtration or an aqueous workup. This new methodology allows the amination of ethereal, benzylic, tertiary, secondary, and even primary C-H bonds. The intramolecular reaction provides an interesting route to various substituted oxazolidinones, whereas the intermolecular reaction gives trichloroethoxycarbonyl-protected amines that can be isolated with moderate to excellent yields and that cleave easily to produce the corresponding free amine. The development, scope, and limitations of the reactions are discussed herein. Isotopic effects and the electronic nature of the transition state are used to discuss the mechanism of the reaction.
Huard, Kim,Lebel, Helene
supporting information; experimental part
p. 6222 - 6230
(2009/05/27)

PROCESS FOR THE PREPARATION OF MEMANTINE
A process for the preparation of Memantine of formula (I) or its pharmaceutically acceptable salts is disclosed. The process comprises formula (I): (a) reacting halogenated-3, 5 -dimethyl adamantine of formula (III) with acetamide in presence of sulfuric acid to provide l-Acetamido-3,5-dimethyl adamantine of formula (II), wherein X is Cl or Br. Formula (III), (II): (b) treating l-Acetamido-3,5-dimethyl adamantine of formula (II) with base in presence of solvent to obtain Memantine of formula (I) (c) optionally converting Memantine of formula (I) in to pharmaceutically acceptable salts.
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Page/Page column 16-17

(2008/12/05)

Process for the preparation of memantine and its hydrochloric acid salt form
The present invention relates to the synthesis of 1-amino-3,5-dimethyladamantane ("memantine") and its hydrochloric acid salt form. In particular a new intermediate (N-chloro-acetylamino-3,5-dimethyladamantane) for the synthesis of memantine as well as a new process for the preparation of memantine and its hydrochloric acid salt form using said intermediate is disclosed.
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Page/Page column 8

(2008/06/13)

A PROCESS FOR THE PREPARATION OF MEMANTINE HYDROCHLORIDE
3,5-Dimethyladamantane is reacted with bromine to form l-bromo-3,5,- dimethyladamantane of formula (I), it is reacted with acetonitrile in the presence of acid to form l-acetamido-3,5-dimethyladamantane of formula (II). Optionally formula (II) is treated with an organic acid to form the corresponding salt of formula (Ill), which is setting free of salt in the presence of base to get the pure formula (II). A formula (II) is subjected to hydrolysis followed by in-situ reaction with hydrochloric acid to form memantine hydrochloride. The memantine hydrochloride is treated with base to get the pure memantine base.
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(2008/06/13)

An improved synthesis of memantine hydrochloride: Anti-Alzhelmer's drug
An economical new process route has been developed for the large-scale synthesis of memantine hydrochloride (1) an anti-Alzheimer's drug. The procedure involves the conversion of 1,3-dimethyl adamantane (2) to formamide intermediate 8 as a key step, followed by hydrolysis to (1-amino-3,5-dimethyl adamantane) hydrochloride (1) in good yield.
Reddy, Jambula Mukunda,Prasad, Ganji,Raju, Veeramalla,Ravikumar, Mylavarapu,Himabindu, Vurumidi,Reddy, Ghanta Mahesh
p. 268 - 269
(2012/12/26)

PROCESS FOR PREPARING MEMANTINE HYDROCHLORIDE SUBSTANTIALLY FREE OF IMPURITIES
The present invention encompasses processes for preparing Memantine hydrochloride and its derivatives, substantially free of impurities.
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(2008/06/13)

New synthetic approach to memantine hydrochloride starting from 1,3-dimethyl-adamantane
A short and practical method for the synthesis of 1-amino-3,5-dimethyl- adamantane (Memantine hydrochloride) was established by using tertiary butyl alcohol under Ritter conditions to give 1-acetamido-3,5-dimethyl-adamantane. The 1-acetamido-3,5-dimethyl-adamantane is hydrolyzed using alkali to give free base which was then converted into its hydrochloride acid.
Madhra, Mukesh K.,Sharma, Mukesh,Khanduri
p. 922 - 923
(2012/12/30)

Process for the preparation of adamantanamines
The present invention concerns a process for the manufacture of an adamantanamine of formula wherein R, R' and X are as defined in the claims, which comprises (i) reacting a compound of formula with thiourea; (ii) subjecting the resulting compound of formula to an acid treatment and (iii) isolating the resulting adamantanamine or a hydrohalogenide thereof. According to the process of the invention, valuable pharmaceuticals are obtainable, such as Memantine hydrochloride (R,R' = methyl), an uncompetitive NMDA(N-methyl-D-aspartate) receptor antagonist used as a new treatment for Alzheimer's disease, or Amantadine hydrochloride (R,R' = hydrogen) used as an antiviral or in the treatment of Parkinson's disease.
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Page/Page column 6; 7

(2008/06/13)

PROCESS FOR THE PREPARATION OF ADAMANTANAMINES
The invention relates to a process for preparing certain adamantanamines, of formula (IV) wherein R, R' are each methyl and X is halogen, to intermediates used in the process, and to processes for preparing such intermediates.
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Page/Page column 11-12

(2010/11/28)

PROCESS FOR PREPARING MEMANTINE
A process for preparing memantine or an acid addition salt of memantine comprises reacting 1-bromo-3,5-dimethyl adamantane with formamide to form 1-N-formyl-3,5-dimethyl adamantane.
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(2008/06/13)

AMINO ADAMANTANE DERIVATIVES, METHODS FOR THE PRODUCTION AND USE THEREOF
The invention relates to 1-amino adamantane derivatives and 3-amino adamantane-1-carboxylic acid derivatives, wherein the 5th and/or 7th position of the adamantane base frame can be substituted in any particular manner. The invention also relates to methods for the production of said inventive compounds, in addition to methods for linking the thus obtained monomer 3-amino adamantane-1-carboxylic acid derivatives in order to form oligomers. The inventive compounds are suitable for use as anti-viral active substances, artificial ion channels and for the therapy, diagnosis and prophylaxis of diseases, wherein a defect of the GA-BA-system occurs.
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Page/Page column 45

(2010/02/15)

Process for synthesising aminoadamantanes
The present invention concerns a new process for synthesising aminoadamantanes of formula I in which R1 and R2 are identical or different and are H or a straight or branched alkyl group comprising from 1 to 6 carbon atoms, and addition salts thereof with inorganic or organic acids, in particular memantine hydrochloride (1-amino-3,5-dimethyladamantane hydrochloride).
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Page/Page column 5; figure 1

(2008/06/13)