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 the problems of complicated operation and high content of related substances, achieve simple operation, reduce the content of related substances, and simplify the production process Effect

Inactive Publication Date: 2013-04-17
NANJING SIMCERE DONGYUAN PHARM CO LTD
View PDF8 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although this method does not use methylamino alcohol or ethyl acetate as a reaction solvent, its operation is also relatively loaded down with trivial details, and the content of related substances in the final product obtained is relatively high

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
  • Preparation method of amlodipine maleate
  • Preparation method of amlodipine maleate
  • Preparation method of amlodipine maleate

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0028] The invention provides a kind of preparation method of amlodipine maleate, comprising the following steps:

[0029] a) react maleic acid and amlodipine free base in water to obtain amlodipine crude product;

[0030] b) refining the crude amlodipine maleate obtained in step a) to obtain amlodipine maleate.

[0031] The present invention uses maleic acid and amlodipine free base as raw materials and water as a reaction medium to prepare amlodipine maleate. The operation is not only simple, but also the content of related substances in the prepared amlodipine maleate is extremely low.

[0032] The present invention uses maleic acid as a raw material, and the maleic acid is also called maleic acid. The present invention has no special limitation on its source, and commercially available products are sufficient.

[0033] The present invention uses amlodipine free base as raw material, and described amlodipine free base is also called amlodipine base, and its molecular formu...

Embodiment 1

[0051] Disperse 1mol of maleic acid and 1.1mol of amlodipine free base in 2.2L of water, stir and react at 10°C for 2h, filter the resulting reaction mixture to obtain the crude product of amlodipine maleate; Dipine crude product is dispersed in ethanol, the ratio of the volume of described ethanol and the quality of described amlodipine maleate crude product is 14L: 1kg, add 0.03g medicinal charcoal after heating to reflux, reflux 30min, drop to room temperature, in- Place crystallization at 5°C for 4h, centrifuge, and then dry at 25°C and >0.08MPa to obtain amlodipine maleate with a yield of 65%.

[0052] Described amlodipine maleate is carried out high performance liquid chromatography analysis, the result sees figure 1 , figure 1 For the high performance liquid chromatogram of the amlodipine maleate prepared by Example 1 of the present invention, by figure 1 It can be seen that the present invention has prepared amlodipine maleate with a purity of 99.7%, a single maximum...

Embodiment 2

[0054] Disperse 2mol of maleic acid and 2.2mol of amlodipine free base in 4.4L of water, stir and react at 15°C for 1h, filter the resulting reaction mixture to obtain the crude product of amlodipine maleate; The dipine crude product is dispersed in ethanol, the ratio of the volume of the ethanol to the mass of the amlodipine maleate crude product is 14L: 1kg, after stirring at -5°C for 4h, suction filtration under reduced pressure, and then at 23°C, > Dry under the condition of 0.08MPa, obtain amlodipine maleate, and yield is 60%.

[0055] Described amlodipine maleate is carried out high performance liquid chromatography analysis, the result sees figure 2 , figure 2 For the high performance liquid chromatogram of the amlodipine maleate prepared by the embodiment of the present invention 2, by figure 2 It can be seen that the present invention has prepared amlodipine maleate with a purity of 99.8%, a single largest impurity of 0.11%, and a total impurity of 0.22%.

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 provides a preparation method of amlodipine maleate, which comprises the following steps that a), maleic acid and amlodipine free alkali react in water, and an amlodipine maleate crude product is obtained; and b), the amlodipine maleate crude product obtained in Step a) is refined, and the amlodipine maleate is obtained. The preparation method takes the water as a reaction medium, and is low in price and environment-friendly; in addition, generation of impurities in a synthetic process is reduced by adjusting parameters such as the use amount of the water, maleic acid and amlodipine free alkali, reaction temperature and reaction time, so that contents of relevant substances in the amlodipine maleate are lower, and the yield of the amlodipine maleate is ensured. A result proves that the yield of the amlodipine maleate prepared by the preparation method is above 55%, the maximum content of the single impurity is less than 0.2%, and the total content of the relevant substances is less than 0.3%.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, in particular to a preparation method of amlodipine maleate. Background technique [0002] Amlodipine maleate is a dihydropyridine calcium antagonist suitable for the treatment of hypertension and angina pectoris. Its English name is Amlodipine Maleate, and its chemical name is 2[(2-aminoethoxy)methyl]-4( 2-Chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylic acid-3-ethyl-5-methyl ester maleate, the molecular formula is C 24 h 29 ClN 2 o 9 , has the formula (I) structure: [0003] [0004] The prior art generally uses amlodipine as the starting raw material, and prepares amlodipine maleate after salting with maleic acid in a solvent. The commonly used solvent is generally methylamino alcohol or ethyl acetate, but these two The solvent is not only expensive, but also needs to add other solvents for subsequent refining treatment, and the operation is cumbersome. The Chi...

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
IPC IPC(8): C07D211/90C07C57/145C07C51/41
Inventor 赵耀军向玉梅李林芳宋林陈汉卫
Owner NANJING SIMCERE DONGYUAN PHARM CO LTD
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