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

One group of novel benzene cyclobutane compounds and application of novel benzene cyclobutane compounds in chemical synthesis

A technology of benzocyclobutane and compound, applied to benzocyclobutane compound and its application field in the preparation of ivabradine, can solve the problem of high preparation cost of ivabradine, high preparation difficulty, complicated operation, etc. problem, to achieve the effect of high product yield, low cost and simple process operation

Active Publication Date: 2012-12-19
江苏宇田医药有限公司
View PDF4 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] From the existing synthetic methods of ivabradine, it can be seen that no matter which method, the preparation cost of ivabradine is high, the preparation is difficult, the operation is cumbersome and the yield is low, and there is a certain bottleneck in industrial scale-up production

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
  • One group of novel benzene cyclobutane compounds and application of novel benzene cyclobutane compounds in chemical synthesis
  • One group of novel benzene cyclobutane compounds and application of novel benzene cyclobutane compounds in chemical synthesis
  • One group of novel benzene cyclobutane compounds and application of novel benzene cyclobutane compounds in chemical synthesis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] Example 1: Compound III is (1S)-[N-(3-(2,2-dimethoxyethylamine)-propyl)-N-methyl]carbamoyl-4,5-dimethoxy Preparation of phenylbenzocyclobutane

[0050] Dissolve 35 mL of aminoacetaldehyde dimethyl acetal and 50 mL of triethylamine in 300 mL of dichloromethane, place the reaction bottle in an ice bath, and dissolve 89.3 g of (1S)-[N-(3-chloropropyl)-N -Methyl]carbamoyl-4,5-dimethoxybenzocyclobutane was dissolved in 450mL of dichloromethane to form a solution, the solution was dropped into the aforementioned reaction solution placed in an ice bath, and stirred at room temperature , saturated with 300 mL NaHCO 3 The organic layer was washed twice, and then washed twice with 300 mL of water. The organic layer was collected, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 98.9 g of a brownish-yellow oily substance, Compound III, with a yield of 90%.

Embodiment 2

[0051] Example 2: Compounds Namely (1S)-[N-(3-(2,2-dimethoxyethylamine)-propyl)-N-methyl]aminomethyl-4,5-dimethoxybenzocyclobutane preparation of

[0052] Pass nitrogen protection into the reaction flask containing 73.3 g of compound III prepared in Example 1, add 350 mL of anhydrous tetrahydrofuran, stir to dissolve, add 10.0 g of lithium tetrahydrogen to the reaction solution in batches under ice bath, and complete the addition , stirred at room temperature for 5 hours, the raw material reaction of the sampling spot plate was complete, slowly added 50 mL of water dropwise to the reaction solution to quench the reaction, added 500 mL of ethyl acetate to the reaction solution, then added anhydrous sodium sulfate, stirred and dried for 2 hours, filtered In addition to desiccant, the filtrate was concentrated under reduced pressure to obtain the residue that is the compound 61.3 g, yield 87%.

Embodiment 3

[0053] Example 3: Compounds That is, N-(3-(N-(((S)-1,2-dihydro-4,5-dimethoxybenzocyclobutane-2-yl)methyl)-N-formamide)propane Preparation of -N-(2,2-dimethoxyethyl)-2-(3,4-dimethoxyphenyl)acetamide

[0054] Add 400 mL of dichloromethane into a 1 L reaction flask, add 39.2 g of 3,4-dimethoxyphenylacetic acid while stirring, cool down to 0°C~5°C in an ice bath, and start adding 28.5 g of thionyl chloride dropwise. Control the rate of addition so that the temperature of the reaction solution does not exceed 10°C, remove the ice-water bath after the addition, stir and react at room temperature for 2 hours, evaporate the solvent to dryness under reduced pressure to obtain a brown oil, add 200 mL of dichloromethane to dissolve, and set aside;

[0055] 350mL contains the compound that 35.2g embodiment 2 prepares Adjust the pH of the dichloromethane solution to 8~9 with triethylamine, add the prepared dichloromethane solution containing brown oil dropwise, control the rate of addi...

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 one group of novel benzene cyclobutane compounds, a method for preparing the novel benzene cyclobutane compounds and a method for preparing ivabradine from the novel benzene cyclobutane compounds for solving the problems of higher synthesis difficulty in the ivabradine with huge medicinal value at present. The invention provides a preparation method for the ivabradine. The method is short in synthetic path and is simple to operate so that the synthesis difficulty of the ivabradine is greatly reduced; and in addition, the method has the advantages of low cost, high yield of products and favorable industrial base and application value.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, and specifically relates to a group of novel benzocyclobutane compounds and their application in the preparation of ivabradine. Background technique [0002] Ivabradine, chemical name: 7,8-dimethoxy-3-(3-[[(1S)(4,5-dimethoxybenzocyclobutan-1-yl)methyl] -methylamino]propyl)-1,3,4,5-tetrahydro-2H-benzazepin-2-one, its structure is shown in the following formula: [0003] [0004] Ivabradine can be used clinically to treat various myocardial ischemia, such as angina pectoris, myocardial infarction and related rhythm disorders. It is a new generation of cardiovascular drugs with very broad treatment prospects. [0005] At present, the synthesis of ivabradine mainly includes the following types: [0006] method one: [0007] [0008] Wherein: R group represents halogen, dioxolane, dioxane and the like. [0009] Method Two: [0010] [0011] Wherein: R group represents haloge...

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): C07C235/40C07C231/12C07C217/58C07C213/02C07C235/34C07C231/02C07D223/16
Inventor 陈言德朱万里
Owner 江苏宇田医药有限公司
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