Preparation method of arbidol hydrochloride

A technology of arbidol hydrochloride and molar ratio, which is applied in the field of medicine and chemical industry, can solve the problems of low total reaction yield, low total yield and the like, and avoid the problems of low reaction yield, low production cost and high yield. Effect

Active Publication Date: 2016-11-09
SHANDONG LUOXIN PHARMA GRP HENGXIN PHARMA CO LTD
View PDF6 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] 2. Song Yanling, Zhao Yanfang, Gong Ping and others reported in the literature "Synthesis of Arbidol Hydrochloride" that the substitution reaction between thiophenol and ethyl chloroacetoacetate occurred first, and the thiophenyl segment in the molecule was introduced, and then combined with Methylamine is condensed, followed by Nenitzescu reaction with p-benzoquinone, dimethylaminomethyl is introduced through Mannich reaction, bromination reaction is carried out after acetyl

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 arbidol hydrochloride
  • Preparation method of arbidol hydrochloride
  • Preparation method of arbidol hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[0039] Example 1-1: Preparation of 4-acetoxyaniline (7)

[0040] P-nitrophenol (9, 1.0mol, 139.1g) was added to 1000mL of acetone, 151.8g (1.5mol) of triethylamine was added, 196.3g of acetyl chloride (2.5mol) was added dropwise at room temperature, the dropwise was completed within 1 hour, and reflux reaction 1 Hours, naturally cooled to room temperature, the reaction solution was poured into 2000g of ice water, stirred, filtered, the filter cake was washed with water, and vacuum-dried to obtain 183.2g of p-nitrophenyl acetate (8) crude product. The next reaction was carried out directly without further purification.

[0041] Add 3000mL of water and 3000mL of ethanol to the reaction flask, add reduced iron powder (139.6g, 2.5mol) and ammonium chloride (133.7g, 2.5mol) under stirring, heat to reflux for 1h, and add the above-prepared p- Nitrophenyl acetate (8, 183.2g), continued to reflux for 2h, and TLC confirmed that the reaction was complete. Stop the reaction, suction fi...

Embodiment 1-2

[0042] Embodiment 1-2: Preparation of 4-acetoxyaniline (7)

[0043] P-nitrophenol (9, 1.0mol, 139.1g) was added to 1000mL of acetone, 158.2g (2mol) of pyridine was added, 196.3g of acetyl chloride (2.5mol) was added dropwise at room temperature, the dripping was completed within 1 hour, and the reaction was refluxed for 3 hours, naturally After cooling to room temperature, the reaction solution was poured into 2000 g of ice water, stirred, filtered, the filter cake was washed with water, and vacuum-dried to obtain 187.5 g of crude p-nitrophenyl acetate (8). The next reaction was carried out directly without further purification.

[0044] Add 3000mL of water and 3000mL of ethanol to the reaction flask, add reduced iron powder (195.5g, 3.5mol) and ammonium chloride (187.2g, 3.5mol) under stirring, heat to reflux for 1h, and add in batches the obtained For p-nitrophenyl acetate (8), the reaction was confirmed to be complete by TLC after continuing to reflux for 2 h. Stop the re...

Embodiment 2-1

[0045] Example 2-1: Preparation of ethyl 5-acetoxy-2-methylindole-3-carboxylate (5)

[0046] Add 2000mL of dichloromethane into the reaction flask, add 4-acetoxyaniline (7, 120.9g, 0.8mol) under stirring, heat to dissolve, add 104.1g of ethyl acetoacetate (6, 0.8mol) and catalyst bromine Indium InBr 3 (8, 2.8g, 0.008mol), after reflux reaction for 2h, TLC confirmed that the reaction was complete. Stop the reaction, suction filter while it is hot, and remove the solvent by rotating the filtrate under reduced pressure to obtain 203.7 g of the enaminone intermediate; the yield is 96.7%. The next reaction was carried out directly without further purification.

[0047] Add 203.7 g of the above-mentioned enaminone intermediate into a reaction flask containing 2000 mL of DMF, and add K respectively under stirring. 2 CO 3 (345.5g, 2.5mol), catalyst Pd(OAc) 2 (9g, 0.04mol), and oxidant Cu(OAc) 2 (480g, 2.4mol), heated to 80°C for 3 hours, TLC confirmed that the reaction was compl...

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 arbidol hydrochloride. P-nitrophenol which is cheap and easy to obtain is innovatively adopted as the raw material, and through acetylation, nitroreduction, an indole ring reaction, a methylation reaction, bromination, a reaction with thiophenol and deprotection, a Mannich reaction and salification, arbidol hydrochloride is obtained. Reaction conditions of the whole synthesis process are mild, the raw material can be conveniently obtained, the character of the product is good, the yield is high, few by-products are generated, reaction selectivity and purity are high, environmental friendliness is achieved, production cost is low, and the method is suitable for industrial production; the defects that in the prior art, selectivity is low, many by-products are generated, the yield is low, precious catalysts are used, and serious environmental pollution is caused are overcome.

Description

technical field [0001] The invention relates to the technical field of medicine and chemical industry, in particular to a preparation method of Arbidol hydrochloride. Background technique [0002] Arbidol hydrochloride, the English name is arbidol hydrochloride, the Chinese chemical name is 1-methyl-4-dimethylaminomethyl-5-hydroxyl-6-bromo-2-phenylthiomethyl-1H-indole-3 - Ethyl carboxylate hydrochloride monohydrate, molecular formula C 22 h 25 BrN 2 o 3 S·HCI·H 2 O, the molecular weight is 531.90. Its chemical structural formula is as follows: [0003] [0004] Arbidol hydrochloride was first listed in Russia in 1993. It is a hydrate for medicinal use, and is suitable for the prevention and treatment of adults and children with influenza A, influenza B, acute viral respiratory infections, severe acute respiratory syndrome, and concurrent bronchitis and pneumonia. Clinical application proves that Arbidol hydrochloride has few side effects and is not easy to produce...

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): C07D209/42
CPCC07D209/42
Inventor 刘新泉蒋燕杰王彦锋
Owner SHANDONG LUOXIN PHARMA GRP HENGXIN PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap