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

Synthesis technology of higenamine and pharmaceutical salt of higenamine

A technology of higenamine base and synthesis process, which is applied in the direction of organic chemistry, can solve the problems of little industrial application value, high cost of raw materials, high risk, etc., and achieve easy control of the reaction process, low post-processing cost, The effect of low production cost

Pending Publication Date: 2019-08-23
珠海市柏瑞医药科技有限公司
View PDF4 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The synthesis method has few steps, simple post-treatment, and the yield is as high as 62%. It does not use highly toxic and dangerous compounds such as phosphorus oxychloride, but its raw material cost is high, and magnesium powder is used in the reaction, which is dangerous and does not have too much risk. Industrial application value

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 technology of higenamine and pharmaceutical salt of higenamine
  • Synthesis technology of higenamine and pharmaceutical salt of higenamine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] (1) Preparation of 4-methoxyphenylacetaldehyde

[0029] Dissolve 24.07g of sodium hydroxide in 500g of water, add 100g of 4-methoxyphenylacetic acid, stir for 30min to completely dissolve the solid, add 38.95g of potassium borohydride and 8.20g of zinc chloride, raise the temperature to 45°C for 3h, and use After TLC monitors that 4-methoxyphenylacetic acid is consumed, 15% hydrochloric acid is added dropwise to neutralize the reaction solution to pH=7, 62.78g of active manganese dioxide is added, and the reaction is continued for 4h. After the reaction is complete, the reaction solution is cooled to room temperature, and 1mol / L sodium hydroxide solution to adjust the pH to 8-9, add 500g of dichloromethane and stir for 1 hour, let stand for liquid separation, take the organic phase, dry it with anhydrous sodium sulfate, and filter to obtain 4-methoxyphenylacetaldehyde solution.

[0030] (2) Preparation of 6,7-dimethoxy-1-(4-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline ...

Embodiment 2

[0035] (1) Preparation of 4-methoxyphenylacetaldehyde

[0036] Dissolve 41.59g of potassium carbonate in 600g of dichloromethane, add 100g of 4-methoxyphenylacetic acid, stir for 40min to completely dissolve the solid, add 22.77g of sodium borohydride and 7.64g of iodine, heat up to 45°C for 2h, and use After TLC monitors that 4-methoxyphenylacetic acid is consumed, 10% hydrochloric acid is added dropwise to neutralize the reaction solution to pH=7, 78.48g active manganese dioxide is added, and the reaction is continued for 3h. After the reaction is complete, the reaction solution is cooled to room temperature, and 1mol / L sodium hydroxide solution to adjust the pH to 8-9, add 600g of water and stir for 1 hour, let stand for liquid separation, take the organic phase and dry it with anhydrous sodium sulfate, filter to obtain 4-methoxyphenylacetaldehyde solution.

[0037] (2) Preparation of 6,7-dimethoxy-1-(4-methoxybenzyl)-1,2,3,4-tetrahydroisoquinoline

[0038] Add 109.06g of ...

Embodiment 3

[0042] (1) Preparation of 4-methoxyphenylacetaldehyde

[0043] Dissolve 41.59g of sodium bicarbonate in 400g of tetrahydrofuran, add 100g of 4-methoxyphenylacetic acid, stir for 60 minutes to completely dissolve the solid, add 103.13g of sodium thioborohydride and 4.04g of copper chloride, and heat up to 50°C for reaction 3h, after the consumption of 4-methoxyphenylacetic acid was monitored by TLC, 10% hydrochloric acid was added dropwise to neutralize the reaction solution to pH=7, 94.17g active manganese dioxide was added, and the reaction was continued for 5h. After the reaction was complete, the reaction solution was cooled to At room temperature, use 1 mol / L sodium hydroxide solution to adjust the pH to 8-9, add 400 g of water and stir for 1 h, let stand to separate the liquids, take the organic phase, dry it with anhydrous sodium sulfate, and filter to obtain a 4-methoxyphenylacetaldehyde solution.

[0044] (2) Preparation of 6,7-dimethoxy-1-(4-methoxybenzyl)-1,2,3,4-tet...

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 synthesis technology of higenamine and pharmaceutical salt of the higenamine, and belongs to the technical field of medicine synthesis. According to the synthesis technology,4-methoxyphenylacetic acid is used as a raw material, and through steps of reduction, oxidation, cyclization, deprotection and the like, the higenamine and the hydrochloride of the higenamine are obtained. Compared with existing technical routes, the synthesis technology has the few steps, and is simple to operate, the raw material is cheap, reaction conditions are mild, a reaction process is easy to control, the total yield and the purity are high, and the synthesis technology is environmentally friendly, safe and suitable for industrial production, and has large industrial prospects.

Description

technical field [0001] The invention relates to the technical field of medicine synthesis, in particular to a synthesis process of higenamine and medicinal salt thereof. Background technique [0002] Higenamine hydrochloride was originally isolated and extracted from Japanese aconite by Kosuge et al. Studies have shown that higenamine hydrochloride has a strong effect on the cardiovascular system, can accelerate heart rate, reduce diastolic blood pressure, and significantly increase Coronary blood flow, improve sinus node conduction function; good curative effect on sinus bradycardia, myocardial contractility is significantly enhanced. Higenamine hydrochloride also has an effect on the heart conduction system and bronchi. For sinoatrial block and some cases of atrioventricular block (especially type block) in the node area, the conduction block can disappear or be alleviated; Smooth muscle has a relaxing effect. Its unique pharmacological effects and remarkable therapeutic...

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): C07D217/20
CPCC07D217/20
Inventor 王一霖蔡军成
Owner 珠海市柏瑞医药科技有限公司
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