Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Synthetic method for 1-{2-floro-4-[5-(4-isobutyl phenyl)-1,2,4-oxadiazol-3-yl]-benzyl}-3-azetidinecarboxylic acid

A technology of isobutylphenyl and azetidine carboxylic acid, applied in directions such as organic chemistry, can solve problems such as high cost and unfavorable industrial production, and achieve the effects of reducing cost, avoiding the use of a large amount of solvent, and reducing by-products

Active Publication Date: 2016-02-24
SUZHOU CONNECT BIOPHARMACEUTICALS LTD
View PDF1 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] For example, in the preparation of the compound of formula 2, it is necessary to use a large amount of solvent to purify the intermediate compound by column chromatography, resulting in high cost, which is not conducive to industrial production

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
  • Synthetic method for 1-{2-floro-4-[5-(4-isobutyl phenyl)-1,2,4-oxadiazol-3-yl]-benzyl}-3-azetidinecarboxylic acid
  • Synthetic method for 1-{2-floro-4-[5-(4-isobutyl phenyl)-1,2,4-oxadiazol-3-yl]-benzyl}-3-azetidinecarboxylic acid
  • Synthetic method for 1-{2-floro-4-[5-(4-isobutyl phenyl)-1,2,4-oxadiazol-3-yl]-benzyl}-3-azetidinecarboxylic acid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1 Screening of the synthetic method of the present invention——step (1)

[0063] According to the step (1) of Comparative Example 1, the crude compound of formula 1-5 was prepared and characterized, and the purity was 77.25% as determined by LCMS.

[0064] The obtained crude product was screened for crystallization and purification conditions. The crystallization operation is to dissolve the crude product with a crystallization solvent, crystallize at 20°C, filter, and vacuum dry to obtain an off-white solid product which is 2-fluoro-4-[5-(4-isobutyl Phenyl)-1,2,4-oxadiazol-3-yl]-benzyl alcohol, the purity was checked by LCMS.

[0065] First, carry out the above crystallization operation as listed in Table 1 to screen out the preferred crystallization solvent.

[0066] Table 1. Screening of solvents and their dosage for crystallization purification

[0067]

[0068] It can be seen from Table 1 that in the crystallization conditions using a single solvent,...

Embodiment 2

[0077] Example 2 Screening of the synthetic method of the present invention——step (2)

[0078] Step (2) of the inventive method is carried out according to the following process:

[0079] The purified 2-fluoro-4-[5-(4-isobutylphenyl)-1,2,4-oxadiazol-3-yl]-benzyl alcohol solution shown in Formula 1-5 obtained in Example 1 In the reaction solvent, add active manganese dioxide. After heating the reaction solution to reflux and continuing the reaction, the temperature was lowered to room temperature. Filter and collect the light yellow filtrate, dry it with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain 2-fluoro-4-[5-(4-isobutylphenyl)-1 represented by the formula 1-6 as a white solid product, 2,4-Oxadiazol-3-yl]-benzaldehyde, the conversion rate was detected by LCMS.

[0080] First, carry out the above synthesis steps as listed in Table 4, to screen out the preferred reaction solvent. The moles of 2-fluoro-4-[5-(4-isobutylphenyl)-1,2,4-oxadiazol-...

Embodiment 3

[0092] Example 3 Screening of the synthetic method of the present invention——step (3)

[0093] Step (3) of the inventive method is carried out according to the following process:

[0094] At room temperature, 2-fluoro-4-[5-(4-isobutylphenyl)-1,2,4-oxadiazol-3-yl]-benzaldehyde represented by formula 1-6, formula 3-azetidinecarboxylic acid and glacial acetic acid shown in 1-7 were added to the reaction solvent, and stirred at 20°C for 2 hours. Dissolve NaBH3CN in methanol, then add the methanol solution of NaBH3CN dropwise into the reaction system within 1 hour, and stir the reaction at 20°C after the dropwise addition is completed. The reaction solution was filtered, and the filter cake was rinsed with methanol and then dried to obtain the compound of formula 2, which was a white solid 1-{2-fluoro-4-[5-(4-isobutylphenyl)-1,2,4-oxadiene Oxadiazol-3-yl]-benzyl}-3-azetidinecarboxylic acid, the conversion rate was detected by LCMS.

[0095] First, carry out the above synthesis...

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 provides a synthetic method for a compound 1-{2-floro-4-[5-(4-isobutyl phenyl)-1,2,4-oxadiazole-3-yl]-benzyl}-3-azetidinecarboxylic acid represented by a formula 2. The synthetic method is simple in reaction condition, simple and convenient in post-treatment, easy to operate, high in yield, stable in process and suitable for industrial production.

Description

technical field [0001] The application belongs to the technical field of drug synthesis, and specifically relates to the immunomodulatory compound 1-{2-fluoro-4-[5-(4-isobutylphenyl)-1,2,4-oxadiazol-3-yl]- The synthetic method of benzyl}-3-azetidinecarboxylic acid. Background technique [0002] It is well known in the art that lymphocytes require the presence of sphingosine-1-phosphate receptors (S1P1) to export from lymphoid tissues and enter the peripheral circulation, and that internalization of S1P1 prevents lymphocytes from exporting from lymphoid tissues and transfer these important Immune cells are confined to lymphoid tissue. [0003] Numerous studies have shown that there are a variety of S1P1 receptor agonists that bind to cognate receptors expressed on lymphocytes and lead to S1P1 receptor internalization, which in turn prevents lymphocyte export. Therefore, S1P1 receptor agonists can reduce the ability of the human body to initiate an immune response by prevent...

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): C07D413/10
Inventor 郑伟潘武宾
Owner SUZHOU CONNECT BIOPHARMACEUTICALS 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
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