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

The preparation method of flutermide

A technology of teriflunomide and acetamide, which is applied in the field of preparation of teriflunomide, can solve the problems of long route, low yield, unfavorable to actual production, etc., and achieve mild reaction conditions and high yield Effect

Inactive Publication Date: 2015-12-02
WUHAN INSTITUTE OF TECHNOLOGY
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The route is long and the yield is low, which is not conducive to actual 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
  • The preparation method of flutermide
  • The preparation method of flutermide
  • The preparation method of flutermide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Preparation of intermediate cyanoacetyl chloride: In a three-necked flask, add 1.7g cyanoacetic acid (0.02mol), anhydrous ether 20mL, stir and dissolve, then add 8.3g phosphorus pentachloride (0.04 mol), at the beginning of addition, the reaction temperature rose rapidly, and then gradually stabilized at 10°C. After the addition was complete, stir for 1 hour. The reaction equation is as follows:

[0015]

[0016] Then the solvent was evaporated under reduced pressure, and the solution turned yellow. 20 mL of toluene was added, and the solvent was removed under reduced pressure to obtain a brown liquid. The intermediate was not purified and was used for future use.

[0017] Preparation of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide: Add 2.254g p-trifluoromethylaniline (0.014mol) and 10ml (0.126mol) of pyridine to the reaction flask, and anhydrous Take 20ml of diethyl ether, cool in an ice bath, add 1.22g (0.012mol) of cyanoacetyl chloride obtained in the previous...

Embodiment 2

[0025] The preparation of the cyanoacetyl chloride of embodiment 2 and the preparation of 2-cyano group-N-(4-trifluoromethyl-phenyl)-acetamide are the same as embodiment 1, difference is: the intermediate prepared in embodiment 1 Add 0.8g (0.0035mol) of 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide to 10mL of acetonitrile, and add 1.42g (0.0141mol) of triethylamine under ice-bath conditions to complete the addition After cooling to -15°C, 0.444 g of acetyl chloride (0.0056 mol) was added dropwise. The reaction was violently exothermic, and the solution gradually turned reddish brown. After the addition of acetyl chloride, the ice bath was removed and the temperature was slowly raised to room temperature.

[0026] After reacting for 5 hours, the solution gradually turned light yellow, and was subjected to suction filtration, and the filter cake of the suction filtration was detected by TLC to have no product. The filtrate was adjusted to pH = 2 with 10% hydrochloric acid. Du...

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 relates to a preparation method of teriflunomide. The preparation method comprises the following steps: mixing cyano acetyl chloride, p-trifluoromethylaniline and an acid-binding agent according to the molar ratio of 1:(1-3):(8-11), and reacting to obtain 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide; mixing 2-cyano-N-(4-trifluoromethyl-phenyl)-acetamide, acetyl chloride and an acid-binding agent according to the molar ratio of 1:(1-5):(1-5) of reaction materials, and reacting to obtain teriflunomide. The process has the advantages that the raw materials are easily available, the reaction condition is mild and the yield is high, and the preparation method is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of Teriflunomide. technical background [0002] Teriflunomide, chemical name: (Z)-2-cyano-3-hydroxy-N-[4-(trifluoromethyl)-phenyl]-2-butenamide. It is a dihydroorotate dehydrogenase (DHODH) inhibitor developed by Sanofi-Aventis (France), which is a kind of rheumatoid arthritis treatment drug Leflunomide (Leflunomide) The active metabolite, fluotetamine, is an orally administered anti-inflammatory drug that blocks the proliferation of T and B cells and is used in the treatment of multiple sclerosis. At present, the known mechanism of action of this product includes preventing the de novo synthesis of pyrimidine in lymphocytes by inhibiting dihydroorotate dehydrogenase (DHODH), and interfering with the activity of tyrosine kinase. The drug has broad development prospects. [0003] At present, the industrial production of flutermide mainly involves the condensation of ethyl acetoacetate and triethyl orthofo...

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 Patents(China)
IPC IPC(8): C07C255/23C07C253/30
Inventor 巨修练杜嘉文邓艳丽
Owner WUHAN INSTITUTE OF TECHNOLOGY
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