Check patentability & draft patents in minutes with Patsnap Eureka AI!

Preparation method of nitazoxanide

A technology of nitazoxanide and nitrothiazole, which is applied in the field of preparation of nitazoxanide, can solve the problems of low solubility, large environmental pollution, and high cost, and achieve the effects of high yield, high product purity, and short cycle time

Inactive Publication Date: 2015-12-23
杭州仟源保灵药业有限公司
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The disadvantage of this method is that: using DCC as a condensation agent, 1,3-dicyclohexyl urea (DCU), which is difficult to handle, will be produced in the reaction. DCU will still remain after extraction with ethyl acetate, and recrystallization will also exist in In the finished product, affect the quality of the finished product
The shortcoming of this method is: preparation of acetylsalicyloyl chloride needs to use reagents such as thionyl chloride, phosphorus oxychloride, bigger to environmental pollution, simultaneously 2-amino-5-nitrothiazole in solvents such as acetone, dichloromethane The solubility is not high, the final reaction is not thorough enough
The disadvantages of this method are: acetylsalicyloyl chloride is unstable and not easy to preserve; THF solvent has a higher price and higher cost

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 nitazoxanide
  • Preparation method of nitazoxanide
  • Preparation method of nitazoxanide

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0019] A preparation method of nitazoxanide according to the present invention, the preparation method is: using acetylsalicylic acid represented by formula (I) as raw material, and 2-amino-5 -Nitrothiazole reacts in the presence of a condensation agent and a catalyst, the reaction mixture is cooled to room temperature, filtered, pickled, dried, concentrated, refined to obtain the compound shown in the corresponding formula (III);

[0020]

[0021] The condensing agent described in the present invention is selected from N,N'-carbonyldiimidazole (CDI), 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3- One of tetramethyluronium hexafluorophosphate (HATU), benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU);

[0022] The catalyst is selected from one of 4-dimethylaminopyridine (DMAP), 1-hydroxybenzotriazole (HOBt), N-hydroxy-7-azabenzotriazole (HOAt);

[0023] In the reaction process, a reaction solvent A is also added, and the reaction solvent A is selected from N,N-...

Embodiment 1

[0026] Add 20g of acetylsalicylic acid into 200ml of anhydrous tetrahydrofuran, add 1.0g of DMAP, add 29g of CDI in batches at room temperature, stir for 2-3 hours, add 13g of 2-amino-5-nitrothiazole and 100ml of tetrahydrofuran dropwise at 0-5°C After the dropwise addition, raise the temperature and reflux to react for 24 hours, cool to room temperature, filter, add saturated sodium bicarbonate 100ml to the filter cake and stir for 20 minutes, 100ml of water and stir for 20 minutes, rinse with ethanol to obtain the crude product, then use DMF and methanol Recrystallization gave 11.3 g of nitazoxanide.

Embodiment 2

[0028] Add 20g of acetylsalicylic acid into 200ml of anhydrous DMF, 3g of HOBt, add 14g of 2-amino-5-nitrothiazole, cool to 0°C, add 17g of HATU in batches, heat up to room temperature and react for 10 hours, concentrate, add dichloromethane and stir , filtered to obtain the crude product, then the crude product was added to 100ml of 1mol / L hydrochloric acid and stirred for 20 minutes, filtered, stirred in 100ml of saturated sodium bicarbonate for 20 minutes, recrystallized from DMF and methanol to obtain 8.75g of nitazoxanide. Yield 36%.

[0029] Structure analysis

[0030] 1. UV absorption spectrum

[0031] Instrument: HITACHIU-3010 UV Analyzer

[0032] Solvent: ethanol, 0.1mol / L hydrochloric acid, 0.1mol / L sodium hydroxide

[0033] 1) Measurement data

[0034] The ultraviolet-visible spectral data of table 1 sample

[0035]

[0036] 2) Analysis

[0037] The maximum UV absorption of the sample in ethanol solution is λ max =204nm, ε=2.17×10 4 , for the unsaturated ...

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

Disclosed is a preparation method of nitazoxanide. The preparation method comprises the steps that acetylsalicylic acid shown in the formula I is used as a raw material which reacts with 2-amino-5-nitrothiazole shown in the formula II under the existence of a condensing agent and a catalyst, and a reaction mixture is cooled to the room temperature to be filtered, pickled, dried, concentrated and refined to obtain a compound shown in the corresponding formula III, wherein the condensing agent is selected from one of N,N'-CDI, 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-HATU and benzotriazole-N,N,N',N'-HBTU, and the catalyst is selected from one of 4-DMAP, 1-HOBt and N-hydroxyl-7-HOAt. A reaction solvent A is added in the reaction process and is selected from one or a mixture of N,N-DMF, N,N-DMAC, tetrahydrofuran and dichloromethane.

Description

technical field [0001] The invention relates to a preparation method of nitazoxanide. technical background [0002] With the continuous emergence of drug-resistant strains and drug-resistant insect strains, people are investing a lot of manpower, material and financial resources to develop new antibacterial and insect-resistant drugs. In the 1970s, Romark Laboratories successfully developed a new type of broad-spectrum antibacterial and anti-parasitic drug - nitazoxanide. The characteristics of Helicobacter have aroused people's high attention and concern. [0003] Nitazoxanide is a kind of veterinary drug, which is a noteworthy new development since the advent of benzoimazole drugs for more than 30 years. It was pioneered by Romark Laboratories in 1976 and was originally used for the treatment of tapeworm infection. compound. Nitazoxanide was listed as an antiparasitic drug for the first time in Mexico, with English trade names: Daxon and Colufase; later, it was launched...

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): C07D277/58
CPCC07D277/58
Inventor 汤建拓徐承智陈丹龙李福高邵婷婷赵源虞英民
Owner 杭州仟源保灵药业有限公司
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com