Supercharge Your Innovation With Domain-Expert AI Agents!

Moxidectin intermediate and preparation method thereof, and preparation method of moxidectin

A technology for moxidectin and intermediates, applied in the field of medicinal chemistry, can solve the problems of expensive protective reagents, low intermediate yields, and unsuitability for large-scale industrial production

Active Publication Date: 2022-06-07
河北美荷药业有限公司
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the protective reagents for hydroxyl are mainly chlorosilanes and aryl formyl chlorides, such as tert-butyldimethylsilyl chloride, p-nitrobenzoyl chloride, benzoyl chloride, 4-chlorophenoxyacetyl chloride, etc., but existing These protective reagents are not suitable for large-scale industrial production, because the intermediate yield obtained after the protection is low, and the price of the protective reagent is expensive, and even some protective reagents such as p-nitrobenzoyl chloride and benzoyl chloride are tubes. products, highly toxic

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
  • Moxidectin intermediate and preparation method thereof, and preparation method of moxidectin
  • Moxidectin intermediate and preparation method thereof, and preparation method of moxidectin
  • Moxidectin intermediate and preparation method thereof, and preparation method of moxidectin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] The present embodiment provides a kind of preparation method of moxidectin, comprises the following steps:

[0066] Nucleophilic substitution reaction (protection on hydroxyl group): Synthesis of 5-oxo(β-phenylacryloyl)nemoctine (moxidectin intermediate) from nemoctine

[0067] At room temperature (20-25°C), in a 250mL three-necked flask equipped with a stirrer, add 25g (41.0mmol) nimoctine, 3.3g DMAP (4-dimethylaminopyridine) and 100mL dichloromethane, After stirring and dissolving completely, add triethylamine (17.5mL) and 6.83g β-phenylacryloyl chloride (41.0mmol) successively, stir at room temperature (20-25°C) for 2h until the reaction is complete, then transfer the reaction solution to a 250mL container In a 500mL beaker of sodium bicarbonate solution (5wt%), after stirring for 10min to uniformity, then stand for 20min to separate layers, move the lower organic phase to a 250mL Erlenmeyer flask, add 50g of anhydrous magnesium sulfate for drying, and place overnigh...

Embodiment 2

[0087] The present embodiment provides a kind of preparation method of moxidectin, comprises the following steps:

[0088] Nucleophilic substitution reaction (protection on hydroxyl group): Synthesis of 5-oxo(β-phenylacryloyl)nemoctine (moxidectin intermediate) from nemoctine

[0089] At room temperature (20-25°C), in a 250mL three-necked flask equipped with a stirrer, add 25g (41mmol) nimoctine, 3.5g DMAP (4-dimethylaminopyridine) and 100mL dichloromethane, stir After completely dissolving, add triethylamine (25mL) and 6.83g β-phenylacryloyl chloride (41mmol) successively, stir at room temperature (20-25°C) for 1.75h until the reaction is complete, then transfer the reaction liquid to 250mL bicarbonate In a 500mL beaker of sodium solution (5wt%), stir for 10min until uniform, then let stand for 20min to separate layers, move the lower organic phase to a 250mL Erlenmeyer flask, add 50g of anhydrous magnesium sulfate to dry, and place overnight. The dried liquid was filtered a...

Embodiment 3

[0097] The present embodiment provides a kind of preparation method of moxidectin, comprises the following steps:

[0098] Nucleophilic substitution reaction (protection on hydroxyl group): Synthesis of 5-oxo(β-phenylacryloyl)nemoctine (moxidectin intermediate) from nemoctine

[0099] At room temperature (25-30°C), in a 250mL three-neck flask equipped with a stirrer, add 25g (41mmol) nimoctine, 3.0g DMAP (4-dimethylaminopyridine) and 100mL dichloromethane, stir After complete dissolution, add triethylamine (34mL) and 6.83g β-phenylacryloyl chloride (41mmol) in sequence, stir at room temperature (25-30°C) for 1.5h until the reaction is complete, then transfer the reaction solution to 250mL bicarbonate In a 500mL beaker of sodium solution (5wt%), stir for 10min until uniform, then let stand for 20min to separate layers, move the lower organic phase to a 250mL Erlenmeyer flask, add 50g of anhydrous magnesium sulfate to dry, and place overnight. The dried liquid was filtered and ...

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 moxidectin intermediate and a preparation method thereof, and a moxidectin preparation method. The preparation method of the moxidectin intermediate comprises the following steps: carrying out nucleophilic substitution reaction on nemadectin and beta-phenylacryloyl chloride, and after the reaction is finished, carrying out post-treatment to obtain the moxidectin intermediate. According to the preparation method of the moxidectin intermediate provided by the invention, beta-phenyl acryloyl chloride is adopted as a protective reagent of hydroxyl, after the reaction is finished, post-treatment (column chromatography) purification is performed, the purity of the obtained moxidectin intermediate reaches 98% or above, the yield reaches 92% or above, the cost is low, the reaction time is short, and the method is suitable for industrial production. The method is suitable for large-scale industrial safety production.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a moxidectin intermediate and a preparation method thereof, and a preparation method of moxidectin. Background technique [0002] Moxidectin (MOD), also known as moxidectin or moxidectin, is a semi-synthetic single-component macrolide antibiotic produced by the fermentation of streptomycin. MOD belongs to the milbemyeins (milbemyeins) family, is a macrolide antibiotic with a single structure derived from nemadectin chemically modified or derived, and belongs to the third generation of avermectins (AVMs) drugs . MOD has good anthelmintic activity, as well as long-acting and safe characteristics. It is a broad-spectrum, efficient and safe new macrolide anthelmintic antibiotic widely used in veterinary clinics. [0003] Most of the existing moxidectin preparation methods use nimoctine as a raw material, and obtain it through four-step chemical modification of hydroxyl ...

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
Patent Type & Authority Applications(China)
IPC IPC(8): C07D493/22
CPCC07D493/22Y02P20/55
Inventor 孟冽王卫华孟藏锐赵军华赵云飞王志强张乾梁妍王晓雷
Owner 河北美荷药业有限公司
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