A New Synthetic Method for Fingolimod

A new synthesis and compound technology, applied in the field of new synthesis of the multiple sclerosis drug fingolimod, which can solve the problems of serious pollution, long reaction route, and potential safety hazards

Active Publication Date: 2021-06-29
广州明药科技有限公司
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] 1. The reaction route is generally long, the post-processing is difficult, the pollution is serious, the total yield is low, and the preparation cost is high;
[0007] 2. Some synthetic processes need to use flammable lithium aluminum tetrahydrogen, which has certain potential safety hazards;
[0008] 3. Some intermediates have poor stability and are not easy to store
Such as 2-(4-n-octylbenzene)chloroethane, which is not suitable for industrial production;
[0009] 4. Some raw materials are not easy to obtain, such as 2-amino-2-hydroxymethyl-1,3-propanediol, which is difficult to meet the growing market demand

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
  • A New Synthetic Method for Fingolimod
  • A New Synthetic Method for Fingolimod
  • A New Synthetic Method for Fingolimod

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Under nitrogen protection, triisopropylchlorosilane (TIPSCl, 4.7 mL, 22mmol). After dropping, the temperature was raised to room temperature for 36 hours of reaction. The reaction was quenched with saturated ammonium chloride, and the organic phase was separated by liquid separation. The organic phase was dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated to obtain 4.722 g of compound 3. The reaction product was directly used in the next reaction without purification.

[0025] Two, the synthesis of compound 5

Embodiment 2

[0027] Add palladium acetate (6.7mg, 0.03mmol), glyoxylic acid (4.44mg, 0.06mmol), silver trifluoroacetate (99.4mg, 0.45mmol), acetic acid (1mL), hexafluoroisopropanol (1mL) into the reaction flask ), compound 3 (142 mg) and compound 4 (104 mg, 0.45 mmol). After stirring and reacting at room temperature for 15 minutes in an airtight chamber, the temperature of the reaction solution was raised to 100° C. for 15 hours. After the reaction was completed, the reaction liquid was cooled to room temperature, and the reaction liquid was concentrated under reduced pressure. The concentrated solution was added with 0.3 M aqueous sodium hydroxide solution (10 mL), extracted with dichloromethane, separated, the organic phase was dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain compound 5 as a brown oil. The product was directly used in the next reaction.

[0028] 3. Synthesis of Compound 1

Embodiment 3

[0030] Compound 5 obtained in the previous step reaction was dissolved in tetrahydrofuran (8 mL) at 0° C., pyridine hydrofluoride (2 mL) (70%) was added dropwise to the solution, stirred for 1 hour and then warmed to room temperature for 20 hours. After the reaction was completed, 20 mL of an aqueous solution in which 10 g of sodium carbonate was dissolved was added dropwise to the reaction solution at 0°C. Extract with ethyl acetate (2×50 mL), separate the layers, and dry the organic phase over anhydrous sodium sulfate. Concentrate under reduced pressure, and the concentrate is treated with 10 mL of ether and 8 mL of 0.5M hydrochloric acid. The layers were separated, the organic phase was washed with 0.5M hydrochloric acid (3×8 mL), and the aqueous phases were combined. The aqueous phase was adjusted to a pH greater than 12 with sodium hydroxide. The aqueous phase was extracted with ethyl acetate (2×50 mL), the layers were separated, and the organic phase was dried over anh...

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 new synthesis method of fingolimod. The method comprises the following steps: step 1, compound 2 undergoes silicon ether protection reaction under alkaline conditions, and protects the hydroxyl group in compound 2 to obtain compound 3; step 2. The compound 3 and the compound 4 that have protected the hydroxyl group are reacted through a coupling reaction to generate fingolimod that is protected by the hydroxyl group, that is, compound 5; step 3, the compound 5 generated by the reaction in step 2 is dehydroxylated to generate the target Compound fingolimod (Compound 1). The method has easy-to-obtain raw materials, short synthesis steps, environmental friendliness, convenient post-treatment and good industrial production value.

Description

technical field [0001] The present invention relates to a new synthesis method of Fingolimod (Fingolimod, 1) for treating multiple sclerosis. Background technique [0002] Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system. It can cause a variety of symptoms, including sensory changes, visual disturbances, muscle weakness, depression, difficulties with coordination and speech, severe fatigue, cognitive impairment, balance disturbances, body heat and pain, and can lead to mobility impairment and disability in severe cases. Multiple sclerosis affects nerve cells -- neurons -- in the brain and spinal cord. Neurons transmit information, forming thoughts and feelings that allow the brain to control the body. The fatty layer that protects these neurons is myelin sheath, which assists neurons in the transmission of electrical signals. Multiple sclerosis progressively causes plaque-like destruction (demyelination) of the nerve myeli...

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): C07C213/00C07C215/28
CPCC07C213/00C07F7/1804C07F7/188C07F7/1892C07C215/28Y02P20/55
Inventor 叶其壮葛海波梅以成肖利群
Owner 广州明药科技有限公司
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
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap