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Preparation method of memantinehydrochloride

A technology of memantine hydrochloride and dimethyladamantane, which is applied in the chemical field, can solve the problems of reducing production costs, increasing yields, and chloroform is harmful to humans, and achieves the effects of reducing production costs, reducing steps, and increasing yields

Inactive Publication Date: 2012-07-04
STAR LAKE BIOSCI CO INC ZHAOQING GUANGDONG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method has the following disadvantages: acetonitrile, benzene, ether and other reagents that are harmful to the environment and human body are used in the process of acetamidolation and recrystallization; after acetamidolation, it needs to be extracted with benzene, dried, concentrated, and purified to obtain 1- Acetylamino-3,5-dimethyladamantane can be subjected to alcoholysis reaction, and the steps are long, which is not conducive to improving yield and reducing production cost
Although this method replaces ether with chloroform, chloroform is still a harmful solvent to the human body; in addition, the acetamido reaction of this method still uses expensive, toxic acetonitrile and sulfuric acid as reaction reagents, using these reagents naturally Potential danger of personal injury

Method used

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  • Preparation method of memantinehydrochloride

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Experimental program
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Effect test

Embodiment 1

[0017] Weigh 100g of 1-bromo3,5-dimethyladamantane and 50g of acetamide respectively, mix 1-bromo3,5-dimethyladamantane and acetamide evenly, heat and melt, and the internal temperature reaches 120°C; After 2 hours, add 1000ml of ethylene glycol, 65g of sodium hydroxide, 100ml of water, and the internal temperature reaches 130°C; after 20 hours of reaction, cool to room temperature, add toluene for extraction twice, combine the organic phases, wash with water, concentrate under reduced pressure to obtain a yellow transparent The liquid is 1-amino-3,5-dimethyladamantane, add 150ml of ethanol, add concentrated hydrochloric acid and heat to dissolve to obtain a white solid, filter it with suction, and recrystallize with ethanol to obtain 65.0g of memantine hydrochloride with a yield of 70.1% ( GC99.4).

Embodiment 2

[0019] Weigh 100g of 1-bromo3,5-dimethyladamantane and 70g of acetamide respectively, mix 1-bromo3,5-dimethyladamantane and acetamide evenly, heat and melt, and the internal temperature reaches 120°C; After 2 hours, add 1000ml of diethylene glycol, 65g of potassium hydroxide, and 100ml of water, and the internal temperature reaches 130°C; after 20 hours of reaction, cool to room temperature, add ethyl acetate to extract twice, combine the organic phases, wash them with water, and concentrate under reduced pressure to obtain The yellow transparent liquid is 1-amino-3,5-dimethyladamantane. Add 150ml of ethanol, add concentrated hydrochloric acid and heat to dissolve to obtain a white solid, filter it with suction, and recrystallize with ethyl acetate to obtain 66.0g of memantine hydrochloride. The yield was 71.0% (GC99.1).

Embodiment 3

[0021] Weigh 100g of 1-bromo3,5-dimethyladamantane and 65g of acetamide respectively, mix 1-bromo3,5-dimethyladamantane and acetamide evenly, heat and melt, and the internal temperature reaches 120°C; After 2.5 hours, add 1000ml of ethylene glycol, 70g of sodium bicarbonate, and 100ml of water, and the internal temperature reaches 130°C; after 22 hours of reaction, cool to room temperature, add toluene to extract twice, combine the organic phases, wash with water, and concentrate under reduced pressure to obtain a yellow transparent The liquid was 1-amino-3,5-dimethyladamantane, 170ml of ethanol was added, concentrated hydrochloric acid was added and heated to dissolve to obtain a white solid, which was filtered by suction and recrystallized with ethanol to obtain 66.2g of memantine hydrochloride with a yield of 71.5% ( GC99.2).

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Abstract

The invention discloses a preparation method of memantinehydrochloride, which comprises the steps of enabling 1-bromine-3,5-dimethyl adamantane and acetamide to have amination reaction at the reaction temperature of 50-180 DEG C and with the response time for 0.25-10 hours, directly adding alcohol and inorganic aqueous alkali after completion of the amination reaction at the temperature of 100-200 DEG C for 1-30 hours, obtaining extraction matters through organic solvent extraction, enabling the extraction matters to be reacted with muriatic acid to obtain coarse products of the memantinehydrochloride, and obtaining target products of the memantinehydrochloride through recrystallization of the coarse products of the memantinehydrochloride by using recrystallization solvent finally. The preparation method avoids using toxic chemical reagents, simplifies operating steps, improves yield coefficient, and lowers production cost.

Description

technical field [0001] The invention relates to the field of chemistry, in particular to a preparation method of memantine hydrochloride used as a drug for treating dementia and an N-methyl-D-aspartic acid (NMDA) receptor antagonist. Background technique [0002] Memantine hydrochloride is a new type of anti-Alzheimer's drug, which was first developed by the German company Merz and launched in Germany as Akatinol Memantine in 1984. The trade name was launched for sale, and it was approved for listing in Europe and the United States in February 2002 and October 2003, respectively. Memantine hydrochloride acts on the glutamine system in the brain and is a non-competitive N-methyl-D-aspartic acid (NMDA) antagonist with moderate affinity. NMDA antagonists have the potential to prevent neuronal damage and death due to altered conditions, including neuropathic pain, Alzheimer's disease, chorea and AIDS-induced dementia. In addition, memantine hydrochloride is also the first NMD...

Claims

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Application Information

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IPC IPC(8): C07C211/38C07C209/62C07C209/68
Inventor 龚美义郑明英纪业明宁异真万响林梁健富
Owner STAR LAKE BIOSCI CO INC ZHAOQING GUANGDONG