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

A kind of preparation method of amlodipine key intermediate

A technology of amlodipine and intermediates, which is applied in the field of drug synthesis, can solve the problems of increasing equipment investment, cost of raw materials and solvents, "three wastes" treatment costs, and high price of McBurney's acid, and achieves easy large-scale industrial production and low raw material prices Inexpensive and easy-to-obtain raw materials

Active Publication Date: 2021-10-12
CHANGZHOU UNIV
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] Compared with the method of the present invention, the disadvantage of the route reported by US6562983 is that McBurney's acid is expensive, and the unit price is 2.5 times that of monoethyl malonate potassium salt. In addition, the synthetic route has two more steps than the present invention, which means It is necessary to add two more sets of reaction and post-processing equipment, which increases equipment investment, raw materials, solvent costs and corresponding "three wastes" treatment costs

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 key intermediate
  • A kind of preparation method of amlodipine key intermediate
  • A kind of preparation method of amlodipine key intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] The synthesis of embodiment 1,2-(2-(1,3-dioxoisoindoline-2-yl) ethoxy) acetaldehyde

[0033]

[0034] Add 39.7g of oxalyl chloride in dichloromethane solution (200mL) into a 500mL three-necked flask, cool to -60°C, slowly drop in 30.9g of DMSO in dichloromethane solution (50mL), keep stirring for 0.5 h, add dropwise 47.8g of 2-[2-(2-hydroxyethoxy)ethyl]isoindoline-1,3-dione in dichloromethane solution (100mL), and keep warm at -60°C 2h, then slowly drop 61g of triethylamine, keep warm for 0.5h, then naturally warm up to room temperature. Wash 3 times with 5% dilute sulfuric acid (the aqueous phases are combined to adjust to alkaline, dichloromethane extraction can recover triethylamine, the recovery rate> 98%), the organic phase is washed 2 times with saturated brine, and dried over anhydrous sodium sulfate , filtered, and the solvent was evaporated to dryness to obtain a pale yellow oil, which was directly used in the next reaction without further purification. 1 ...

Embodiment 2

[0041] Embodiment 2, the synthesis of (2-(1,3-dioxaisoindoline-2-yl)ethoxy)-3-oxabutanoic acid ethyl ester (1)

[0042]

[0043] Add 3.5g of stannous chloride in dichloromethane solution (20mL) into a 500mL three-necked flask, cool to 0°C, dissolve 20.9g of ethyl diazoacetate in dichloromethane solution (80mL), dropwise into the three-necked flask, keep warm and stir for 10min, add 42.4g of (2-phthalimideethoxy) acetaldehyde in dichloromethane solution (150mL) into the three-necked flask, naturally raise the temperature to 25°C and keep it warm until The reaction ended (TLC monitored the progress of the reaction). The reaction solution was washed successively with saturated brine and saturated sodium thiosulfate solution, dried over anhydrous sodium sulfate, filtered, 2 g of silica gel was added to the filtrate, stirred for 0.5 h, filtered, and the filtrate was evaporated to dryness to obtain a light brown oil. 1 H NMR (300MHz, CDCl 3 )δ7.88(d×d, J=6.0Hz, 3.0Hz, 2H), 7.75...

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 discloses a preparation method of a key intermediate of amlodipine, and relates to the field of pharmaceutical synthesis. The specific steps are as follows: compound 3 (2-(2-(2-hydroxyethoxy)ethyl)isoindoline-1,3-dione) is obtained by reacting with DMSO (dimethyl sulfoxide) and oxalyl chloride Compound 2 (2-(2-(1,3-dioxaisoindolin-2-yl)ethoxy)acetaldehyde); then compound 2 and ethyl diazoacetate, catalyzed by Lewis (Lewis) acid A C-H bond insertion reaction occurs under the following conditions to obtain compound 1 ((2-(1,3-dioxaisoindolin-2-yl)ethoxy)-3-oxabutyric acid ethyl ester). The preparation method of the present invention avoids the NaH route commonly used in current production, the total yield is equivalent to the NaH route, and the raw materials are cheaper and easier to obtain, thereby greatly improving the safety and production efficiency, and reducing the total cost by about 30%. Suitable for industrial production.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a method for preparing a key intermediate of amlodipine. Background technique [0002] Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist) used for the treatment of various types of hypertension and angina pectoris. Amlodipine has the following three advantages: (1), low incidence of side effects; (2), has a long half-life, only needs to be taken once a day, which greatly improves patient compliance, and can ensure that the drug is administered within 24 hours. (3) Within the therapeutic dose range, it has a strong vasodilation effect, but it does not inhibit myocardial contractility like other conventional calcium antagonists. Therefore, in addition to being used in the treatment of hypertension and angina pectoris, It is very promising to be applied to the treatment of heart failure, which is not available in general calcium antagonists. [0003] The lite...

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): C07D209/48
CPCC07D209/48
Inventor 张跃严生虎辜顺林刘建武岳家委周晨涛朱佳慧李孟金
Owner CHANGZHOU UNIV
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