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

Method for preparing halofuginone intermediate

An intermediate, the technology of hemosanone, which is applied in the field of preparation of hemosanone intermediates, can solve the problems of difficult to complete the reaction, unfavorable large-scale preparation, and difficult post-processing, so as to improve efficiency, reduce the amount of solvent used, and reduce adverse effects Effect

Inactive Publication Date: 2011-05-25
南通远航医药化工有限公司 +1
View PDF0 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0027] The technical problem to be solved by the present invention is to overcome the excessive amount of benzyl chloroformate existing in the preparation method of the existing hemosanone intermediate, the reaction is difficult to carry out completely, the post-processing is difficult, the yield is not high, and it needs to use toxic Larger solvent, higher cost, serious pollution, is not conducive to the defects of large-scale preparation, but provides a new preparation method for hemosanone intermediates, which allows the Van Braun reaction to be carried out completely while reducing chloroformic acid The amount of benzyl ester improves the efficiency of the reaction, and can selectively obtain the 2-position product in the subsequent Claisen rearrangement reaction

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
  • Method for preparing halofuginone intermediate
  • Method for preparing halofuginone intermediate
  • Method for preparing halofuginone intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] The preparation of embodiment 1 compound G

[0048]

[0049] N 2 Under protection, 1.9g (20mmol) of 3-hydroxypyridine was added to 15ml of toluene, and then 2.4ml (21mmol) of benzyl chloride was added at one time, heated to reflux, the insoluble matter gradually disappeared, and the solution was clear. Along with the progress of the reaction, an oily liquid was generated at the bottom of the solution, heated and refluxed for 1 hour, stopped heating, cooled, the oily liquid at the bottom became a solid, poured out the upper layer solution, and the solid was ground with a mortar, then washed three times with ethyl acetate, It was then washed once with ether. After vacuum drying, 4.0 g of compound G was obtained with a yield of 91%, melting point: 159-161°C (literature value: 159-160°C).

Embodiment 2

[0050] The preparation of embodiment 2 compound F

[0051]

[0052] N 2 Under protection, 3.8g (17mmol) of compound G was dissolved in 10ml of methanol, 1.6ml (19mmol) of 3-bromopropene was added, 0.60g (20mmol) of 80% sodium hydride was weighed, added to the above solution in batches, and refluxed for 4 hours , cooled to 0°C, added 0.72g (19mmol) sodium borohydride in batches, and kept at 0°C for 30 minutes. After the reaction, adjust the pH to 5-6 with 3mol / l hydrochloric acid, then adjust the pH to 7-8 with saturated sodium bicarbonate solution, extract with ethyl acetate (10ml×4), combine the organic phases, wash with saturated brine three times, After drying and evaporating the solvent, 2.4 g of the crude product was obtained, which was quickly eluted with a simple short silica gel column (eluent: petroleum ether) to obtain 2.3 g of a colorless oily liquid with a yield of 60%. The structural identification data are as follows: 1 H NMR (CDCl 3 ): δ2.16~2.19(2H, m), 2...

Embodiment 3

[0053] The preparation of embodiment 3 compound D

[0054]

[0055] N 2 Under protection, 6ml (42mmol) of benzyl chloroformate was dissolved in 6ml of tetrahydrofuran, and at 0°C, 2.40g (10.5mmol) of compound F in 6ml of tetrahydrofuran was added dropwise thereto. room temperature and stirred for another 2 hours. Slowly raise the temperature to reflux, recover tetrahydrofuran by atmospheric distillation, then recover about 4ml of benzyl chloroformate by distillation under reduced pressure, and purify the residue by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 20:1) to obtain light yellow Viscous liquid 2.5g, two-step reaction total yield 70%, the structural identification data of the product are as follows: 1 H NMR (CDCl 3 ): δ1.88~1.93(2H, m), 2.41~2.52(2H, m), 3.22~3.26(1H, m), 4.07~4.19(1H, m), 4.58~4.69(1H, m), 5.04 ~5.15 (4H, m), 5.15 (2H, s), 5.51 ~ 5.75 (1H, m), 7.29 ~ 7.36 (5H, m).

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 method for preparing a halofuginone intermediate shown in a formula D or E. The method comprises the following steps of: (1) dropwise adding solution of a compound F into benzyl chloroformate solution, and performing Van Braun reaction to obtain a compound E; and (2) performing Claisen rearrangement reaction on the compound E obtained in the step (1). By the method, the Van Braun reaction can be completely performed, the using amount of benzyl chloroformate is reduced, the efficiency of the reaction is improved, and a 2-bit product can be selectively obtained in the subsequent Claisen rearrangement reaction. In the better embodiment of the invention, the operation process is simplified by a one-pot method, the using amount of solvents is reduced, the selectivity is improved, the cost of the reaction is reduced, the pollution to the environment is reduced, and good conditions are created for mass production of halofuginone.

Description

technical field [0001] The invention relates to a preparation method of a hemosanone intermediate. Background technique [0002] Halofuginone (Hal) is a quinazolinone alkaloid, which is a halogenated derivative of halofuginone, and its hydrobromide is commonly used. Changshanone has strong insecticidal activity, and has a strong inhibitory effect on various chicken coccidia. Adding 3ppm concentration of hemosanone in the feed can effectively control 6 kinds of Eimeria chickens, and can obviously control the clinical symptoms of coccidiosis after treatment, and completely inhibit the discharge of oocysts, so that the environment is no longer polluted, thereby reducing the chance of reinfection possibility. (See J. Johnson, et al, Exp parasitol, 1970, 28: 30; J. Grant, etel. Parasitology Research, 1991, 77: 595) [0003] With the in-depth research on the efficacy and pharmacology of peroxide, it has been found that it can heterosexually inhibit the synthesis of type I colla...

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): C07D211/74
Inventor 陶晓春顾春俊蔡良珍赵韧董于虎
Owner 南通远航医药化工有限公司
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