Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Synthesis method for trans-form amantadine compound

A technology of amantadine and a synthesis method, which is applied in the preparation of organic compounds, chemical instruments and methods, preparation of aminohydroxy compounds, etc., can solve the problems of environmental pressure, complicated operation, lengthy steps, etc., and achieves mild chemical reaction conditions and technology. The technology is mature and the effect of saving a lot of costs

Active Publication Date: 2014-09-10
ASYMCHEM LAB TIANJIN +4
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] 1. Reductive ammoniation with ammonia as an ammonia source (Organic Process Research & Development 2008, 12, 1114-1118): This method uses 2-adamantanone-5-formic acid as a starting material, and is catalyzed by 5% palladium carbon Reductive ammoniation in methanol solution of ammonia to obtain trans-5-carboxylate-2-adamantanamine, the yield is high, the operation is simple, and the reaction conditions are mild, but because the post-treatment operation uses a large amount of acetonitrile and water, it not only greatly increases the production The cost also brings enormous pressure to the environment and is not suitable for large-scale production
[0006] 2. Reductive amination with benzylamine as ammonia source (CN2007 / 80049065.3; (2008) Manufacturing method of hydroxyamantadine): this method uses adamantanone as the starting material, and benzylamine is used as the starting material under sodium borohydride reduction. The ammonium source is ammonified, and amantadine is further prepared by catalytic hydrogenation debenzylation, and the high-purity trans isomer is obtained by refining the diastereomer. Low, will inevitably increase the cost of raw materials and production costs, does not meet the conditions for large-scale production

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method for trans-form amantadine compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] A kind of preparation trans-5-carboxylate-2-adamantanamine The method is characterized in that the specific preparation steps are as follows:

[0030] (1) Add methanol 1169kg (1g / 20mL), 5% Pd / C 5.25kg (1g / 0.07g) and main raw material 2-adamantanone-5-formic acid to the 3000L reactor 75kg;

[0031] (2) The reactor was replaced with nitrogen for 3 times, and after stirring evenly, 164kg (25eq) of liquid ammonia was introduced into the system;

[0032] (3) Control the temperature at 45±2°C, and pass hydrogen at 1.0±0.05MPa until the reaction is complete;

[0033] (4) After the reaction is completed, add 30% sodium methylate methanol solution to the system to make the product completely salify, press filter, wash the filter cake with methanol, combine the filtrates, adjust the acidity with hydrochloric acid to pH=8.3, and centrifuge to obtain the product trans 5 -Carboxylic acid-2-amantadine 66.7kg, yield 88.5%, liquid chromatography purity (HPLC) 99.8%.

Embodiment 2

[0035] A preparation of trans 5-hydroxyl-2-adamantanamine The method is characterized in that the specific preparation steps are as follows:

[0036] (1) Add 711kg of ethanol (1g / 15mL), 10% Pd / C3kg (1g / 0.05g) and 5-hydroxy-2-adamantanone as the main raw material to the 1500L reactor in sequence 60kg;

[0037] (2) The reaction kettle was replaced with nitrogen for 3 times, and after stirring evenly, 123kg (20eq) of liquid ammonia was introduced into the system;

[0038] (3) Control the temperature at 40±2°C, and pass hydrogen at 0.8±0.05MPa until the reaction is complete;

[0039] (4) After the reaction is completed, add 30% sodium ethylate ethanol solution to the system to make the product completely salify, press filter, wash the filter cake with ethanol, combine the filtrates, adjust the acidity to pH=8 with sulfuric acid, and centrifuge to obtain the product trans 5 -Hydroxy-2-adamantanamine 54kg, yield 89.4%, liquid chromatography purity (HPLC): 99.2%.

Embodiment 3

[0041] A kind of preparation trans 2-adamantanamine-5-ammonium sulfonate The method is characterized in that the specific preparation steps are as follows:

[0042] (1) Add 1570kg (1g / 25mL) of isopropanol and 10% Pd(OH) to the 3000L reactor in sequence 2 / C 8kg(1g / 0.1g), 2-adamantanone-5-ammonium sulfonate 80kg;

[0043] (2) The reaction kettle was replaced with nitrogen for 3 times, and after stirring evenly, 178kg (30eq) of liquid ammonia was introduced into the system;

[0044] (3) Control the temperature at 60±2°C, and pass hydrogen at 1.2±0.05MPa until the reaction is complete;

[0045](4) After the reaction is completed, add 30% sodium hydroxide solution to the system to make the product completely salify, press filter, wash the filter cake with isopropanol, combine the filtrates, adjust the acidity with acetic acid to pH=8.5, and centrifuge to obtain the product trans 2-Adamantadine-5-ammonium sulfonate 70kg, yield 87.1%, liquid chromatography purity (HPLC): 99....

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a synthesis method for a trans-form amantadine compound, which includes the steps of utilizing commercialize raw materials on the market or an easily prepared amantadine compound as initial materials, and carrying out reductive amination reaction between the initial raw materials and liquid ammonia under the action of a reductive agent and a catalyst, so that 100% of the trans-form amantadine compound, (wherein R refers to -H, -COOH, -OH, -SO2NH2, Cl and groups shown in the description) is obtained. The method has the advantages that raw materials are easy to obtain, both reaction purity and yield are high, loss of the trans-form amantadine compound is decreased by salifying for final treatment, production cost is reduced, and the method is applicable to large-scale production and provides a novel thinking for preparing the trans-form amantadine compound.

Description

(1) Technical field: [0001] The invention relates to a synthesis method of amantadine, in particular to a synthesis method of trans amantadine compounds. (two) background technology: [0002] Amantadine is an amino derivative of saturated tricyclodecane. It was first discovered in 1964 that it has antiviral effects. It is used for the prevention and early treatment of Asian influenza A virus, and later for the treatment of neurological disorders caused by Parkinson's disease. In recent years, researchers have modified and modified the chemical structure of amantadine, synthesized a series of analogs of amantadine, and found a series of compounds with better efficacy than amantadine and less toxic and side effects, suitable for primary Parkinson's disease, Parkinson's syndrome after encephalitis, drug-induced extrapyramidal reaction, Parkinson's syndrome after carbon monoxide poisoning, and Parkinson's syndrome in the elderly with cerebral arteriosclerosis, such as memantine ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07B43/04C07C229/50C07C227/08C07C215/44C07C213/02C07C311/14C07C309/40
Inventor 洪浩韦建陈元东
Owner ASYMCHEM LAB TIANJIN
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com