A kind of preparation method of amlodipine maleate

A kind of technology of amlodipine maleate and amlodipine, applied in the field of preparation of amlodipine maleate, can solve problems such as long drying time, poor finished product crystal, difficult filtration and the like, achieve easy vacuum filtration, reduce dosage, The effect of shortening the operation time

Active Publication Date: 2016-01-20
NORTHEAST PHARMA GRP
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The main disadvantages of this synthesis process are: 1. The amount of solvent consumed by dissolving raw materials is relatively large; 2. If ethanol or other solvents are used to make salt solvents, the finished product crystals obtained are poor, difficult to filter, and low yield; 3. The drying time in the process is longer, more than 24 hours

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
  • A kind of preparation method of amlodipine maleate
  • A kind of preparation method of amlodipine maleate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Embodiment 1, the preparation of amlodipine maleate salt

[0019] Step 1, preparation of maleic acid solution and amlodipine solution: at 35-40°C, in glass-lined tank 1, dissolve 3.0 kg of solid maleic acid into 7 liters of anhydrous methanol, and the solution Filter under pressure filter 2 into clean glass-lined tank 4; under 20-25°C, in glass-lined tank 1, dissolve 10 kg of solid amlodipine in 15 liters of anhydrous methanol . The solution is passed through a pressure filter 2 into a clean glass-lined tank 3 by means of pressure filtration.

[0020] Step 2, the generation of amlodipine maleate salt: the maleic acid solution prepared in the previous step is slowly added dropwise into the glass-lined tank 3 through the glass-lined tank 4, and the temperature in the reactor is kept at 20-25 ° C. After the addition was complete, the mixture was kept at 20-30°C and stirred for 3 hours, then slowly cooled to 3°C, and the mixture was allowed to stand for 12 hours.

[0021...

Embodiment 2

[0023] Embodiment two, the preparation of amlodipine maleate salt

[0024] Step 1, preparation of maleic acid solution and amlodipine solution: at 35-40°C, in glass-lined tank 1, dissolve 3.5 kg of solid maleic acid into 7 liters of anhydrous methanol, and the solution Filter into a clean glass-lined tank 4 by pressure filter 2 in the manner of pressure filtration; 15 kilograms of solid amlodipine are all dissolved in 15 liters of anhydrous methanol in the glass-lined tank 1 under the condition of 20-25 ° C, and the solution Filter 2 into a clean glass-lined tank 3 through a press filter by means of pressure filtration.

[0025] Step 2, the generation of amlodipine maleate salt: the maleic acid solution prepared in the previous step is slowly added dropwise into the glass-lined tank 3 through the glass-lined tank 4, and the temperature in the reactor is kept at 20-25 ° C. After the addition was complete, the mixture was kept and stirred at 25-40°C for 2 hours, then slowly coo...

Embodiment 3

[0028] Embodiment three, the preparation of amlodipine maleate salt

[0029] Step 1, preparation of maleic acid solution and amlodipine solution: 1.4 kg of solid maleic acid is completely dissolved in 7 liters of anhydrous methanol in glass-lined tank 1 at 35-40 ° C, and the solution is added to The mode of pressure filtration is filtered into clean glass-lined jar 4 by press filter 2; 5 kilograms of solid amlodipine are all dissolved in 15 liters of anhydrous methanol in glass-lined jar 1 under the condition of 20-25 ℃, and solution is added with Press Filtration Method Filter through a press filter 2 into a clean glass-lined tank 3 .

[0030] Step 2, the generation of amlodipine maleate salt: the maleic acid solution prepared in the previous step is slowly added dropwise into the glass-lined tank 3 through the glass-lined tank 4, and the temperature in the reactor is kept at 20-25 ° C. After the addition was complete, the mixture was kept and stirred at 25-50°C for 5 hours,...

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 preparation method of amlodipine maleate. The maleic acid and amlodipine free base are used as starting materials, the maleic acid is added to anhydrous methanol or mother liquor, heated to dissolve, and filtered to obtain a maleic acid methanol solution Add amlodipine free base to anhydrous methanol to dissolve, stir until it is completely dissolved and transparent to obtain amlodipine free base methanol solution; slowly dropwise add the obtained amlodipine free base methanol solution to the obtained maleic acid methanol solution Incubate stirring, cooling, stand for crystallization; the obtained crystals are washed with absolute ethanol and dried to obtain the finished product. The invention establishes an anhydrous methanol reaction system for amlodipine maleate salt formation, the crystal form of the finished product is greatly improved, the vacuum filtration is easy, and the yield is improved, and the mother liquor obtained by filtration after crystallization is used as the next batch of amlodipine to dissolve The solid solvent reduces the consumption of anhydrous methanol, improves the utilization rate of the solvent, saves the cost of solvent treatment, shortens the drying time, and greatly shortens the operation time.

Description

technical field [0001] The invention relates to a preparation method of amlodipine maleate in the field of drug synthesis. Background technique [0002] Amlodipine maleate, the chemical name is rac-2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl- 3,5-Pyridinedicarboxylic acid-3-ethyl-5-methyl ester maleate is mainly used to treat diseases such as hypertension and angina pectoris. Amlodipine maleate is a dihydropyridine calcium channel blocker. Compared with the commonly used calcium channel blockers, it has the characteristics of stable antihypertensive effect, long onset time and less side effects. As a peripheral artery dilator, it acts directly on vascular smooth muscle to reduce peripheral vascular resistance, thereby lowering blood pressure; it can also expand peripheral arterioles and coronary arteries, reduce total peripheral vascular resistance, relieve coronary artery spasm, and reduce cardiac afterload. thereby relieving angina. Amlodipine male...

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): C07D211/90
Inventor 杨亚圣雷健王飞董爱军崔振强陈铮金玉坤
Owner NORTHEAST PHARMA GRP
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
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap