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

Preparation process of bilastine

A bilastine and preparation technology, applied in the field of medicine, can solve the problems of expensive raw materials, low purity and yield, and long reaction route, and achieve the effects of increasing yield, simplifying reaction steps, and ensuring product quality

Pending Publication Date: 2020-04-21
SHANDONG LUOXIN PHARMA GRP HENGXIN PHARMA CO LTD +2
View PDF13 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0019] In this reaction route, compound 2 and compound 7 cannot be purchased from the market, so the reaction route is longer. In addition, in the synthesis process of bilastine, 20 hours of purification are required, which greatly prolongs the process time and reduces the industrial production efficiency.
[0020] In summary, in the prior art, the preparation of bilastine has problems such as expensive raw materials, high toxicity, easy to produce by-products, low purity and yield, and cumbersome process

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 process of bilastine
  • Preparation process of bilastine
  • Preparation process of bilastine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Embodiment 1: the preparation of compound VI

[0040] Add 10.41g of compound III and 52mL of DMF into a 250mL reaction flask, add 13.82g of potassium carbonate, add 7.10g of methyl iodide dropwise under stirring, stir at room temperature for 2h, TLC detects that the reaction is complete (petroleum ether: ethyl acetate=20:1, Rf= 0.35). Add 120 mL of water to the reaction solution, extract three times with 30 mL of ethyl acetate, combine the organic phases, dry with 8.0 g of anhydrous sodium sulfate, filter, concentrate the filtrate, add 80 mL of pre-dried dichloromethane, 19.67 g of triphenylphosphine and 1.70 g of After imidazole was stirred and dissolved, 19.04 g of iodine was added in 10 batches, stirred at room temperature for 2 h, TLC detected that the reaction was complete (petroleum ether: ethyl acetate = 20:1, Rf = 0.45), added 100 mL of saturated aqueous sodium bisulfite solution, and stirred for 30 min , liquid separation, the organic phase was washed successi...

Embodiment 2

[0041] Embodiment 2: the preparation of compound VI

[0042] Add 10.41g of compound III and 52mL of DMF into a 250mL reaction flask, add 8.10g of sodium methoxide, add 7.10g of methyl iodide dropwise under stirring, stir at room temperature for 2h, and TLC detects that the reaction is complete. Add 120 mL of water to the reaction solution, extract three times with 30 mL of ethyl acetate, combine the organic phases, dry with 8.0 g of anhydrous sodium sulfate, filter, concentrate the filtrate, add 80 mL of pre-dried dichloromethane, 20.98 g of triphenylphosphine and 3.40 g of After imidazole was stirred and dissolved, 19.04 g of iodine was added in 10 batches, stirred at room temperature for 2 h, TLC detected that the reaction was complete (petroleum ether: ethyl acetate = 20:1, Rf = 0.45), added 100 mL of saturated aqueous sodium bisulfite solution, and stirred for 30 min , liquid separation, the organic phase was washed successively with 100 mL of saturated aqueous sodium bisu...

Embodiment 3

[0043] The preparation of embodiment 3 compound IV

[0044]Add 10.41g of compound III and 52mL of DMF into a 250mL reaction flask, add 14.78g of lithium carbonate, add 7.10g of methyl iodide dropwise under stirring, stir at room temperature for 2h, and TLC detects that the reaction is complete. Add 120 mL of water to the reaction solution, extract three times with 30 mL of ethyl acetate, combine the organic phases, dry with 8.0 g of anhydrous sodium sulfate, filter, concentrate the filtrate, add 80 mL of pre-dried dichloromethane, 23.61 g of triphenylphosphine and 4.08 g of After imidazole was stirred and dissolved, 19.04 g of iodine was added in 10 batches, stirred at room temperature for 2 h, TLC detected that the reaction was complete (petroleum ether: ethyl acetate = 20:1, Rf = 0.45), added 100 mL of saturated aqueous sodium bisulfite solution, and stirred for 30 min , liquid separation, the organic phase was washed successively with 100 mL of saturated aqueous sodium bisu...

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 belongs to the technical field of medicines, and particularly relates to a preparation process of bilastine. According to the process, esterification, deprotection, iodination and hydrolysis reactions are conducted to generate bilastine. The process is stable in raw material and good in product quality, integrates preparation and refining of bilastine, simplifies reaction steps and improves yield.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a preparation process of bilastine. Background technique [0002] Bilastine is a second-generation histamine H1 receptor antagonist developed by Spain's FAES Pharmaceutical Company. It was approved by the European Union in 2010 for the treatment of allergic rhinitis and chronic idiopathic urticaria. This product is safe, without the sedative effect and cardiotoxicity of commonly used antihistamines. Its chemical structural formula is as follows: [0003] [0004] WO2009102155 reports the synthesis method of bilastine, and its synthesis route is as follows: [0005] [0006] In this method, the synthesis of the key intermediate 2-(4-hydroxyethylphenyl)-2-methyl propionate ethyl is based on p-bromophenylethanol and 1-methoxyl-1-(trimethylsilyl Oxygen) -2-methyl-1-propene as raw material, in the presence of catalyst bis (dibenzylideneacetone) palladium, tri-ter...

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): C07D401/04
CPCC07D401/04
Inventor 宋丽丽王金星张新涛
Owner SHANDONG LUOXIN PHARMA GRP HENGXIN PHARMA CO LTD
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