Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of azelnidipine

A technology of azelnidipine and its compound, which is applied in the field of preparation of azelnidipine, can solve the problems of compound 1 production limitation, etc., and achieve the effects of easy separation, simple operation, and avoiding synthesis

Active Publication Date: 2016-04-06
迪嘉药业集团股份有限公司
View PDF6 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The above reasons cause the production of compound 1 to be greatly restricted

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 azelnidipine
  • Preparation method of azelnidipine
  • Preparation method of azelnidipine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0029] In a 5L reaction flask, add 2L of absolute ethanol, 6g of glacial acetic acid, 8.5g of piperidine and stir for 0.5h at 20~30°C, then add 170g of cyanoacetic acid, 302g of m-nitrobenzaldehyde, and react at 20~30°C for 24h ( TLC central control). Suction filtration after completion of the reaction, the filter cake was rinsed with 200ml of absolute ethanol, and the dried product was 405g, with a yield of 93% and a purity of 98.5%.

[0030] Synthesis of Compound 2

[0031] Add 400g of compound 1, 1.5kg of 30% KOH aqueous solution, and 2L of ethanol into a 5L reaction flask, heat to reflux for 6 hours, cool down to 20~30°C, adjust the pH to 1~2 with industrial hydrochloric acid, a large amount of solids are precipitated, pump Filter, dry product 381g after a small amount of ethanol rinse, yield 88%, purity 99%.

[0032] Synthesis of Compound 3

[0033] In the reaction flask, add 200g of compound 2, 3.5L of tetrahydrofuran and 200g of 1-benzhydryl-3-azetidinol, stir to coo...

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 azelnidipine, which comprises the following steps: carrying out Knoevenagel reaction on cyanoacetic acid and m-nitrobenzaldehyde used as starting materials to generate a compound 1; hydrolyzing cyano group of the compound 1 to generate a compound 2; carrying out esterification on the compound 2 and 1-diphenylmethyl-3-azetidin-ol under the action of DCC (N,N'-dicyclohexylcarbodiimide) to generate a compound 3; carrying out Hantzsch cyclization on the compound 3 and isopropyl 3-aminocrotonate under alkaline conditions to generate an azelnidipine crude product; and refining the crude product to obtain the azelnidipine fine product. The method is simple to operate and suitable for industrial production; and the reaction product is easy to separate.

Description

technical field [0001] The invention relates to a preparation method of azhedipine, which belongs to the technical field of medicine. Background technique [0002] Azedipine is a representative drug of the third-generation dihydropyridines. Compared with the first-generation and second-generation dihydropyridines, it has a longer action time after taking it, and does not cause reflex sympathetic nerve excitation after vasodilation. Response is small and almost no negative myasthenic effect. Due to the above advantages, Azhedipine is favored by more and more patients with hypertension and angina pectoris. [0003] There are two main synthetic methods of Azedipine: [0004] (1) Compound I and compound II are reacted to prepare azeldipine by Hantzsch, such as CN103130700, CN102453023, EP0266922, etc. all adopt this method: [0005] [0006] (2) Compound I, m-nitrobenzaldehyde, and isopropyl acetoacetate are prepared by a one-pot method to prepare azelnidipine, such as CN1...

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): C07D401/12
CPCC07D401/12
Inventor 管西涛梁松军曹德强李路路苗华明
Owner 迪嘉药业集团股份有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap 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