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

Preparation method of lenalidomide for treating multiple myeloma

A technology of lenalidomide and amino, which is applied in the field of drug synthesis, can solve the problems of low product yield and complicated steps, and achieve the effect of simple and convenient preparation and suitable for industrial production

Active Publication Date: 2017-11-10
SHANGHAI WANXIANG PHARMA
View PDF6 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The purpose of the present invention is to overcome the defects of complicated steps and low product yield in the existing method for preparing lenalidomide, and provide a method for preparing lenalidomide that is more suitable for industrial scale production and has high yield and mild conditions

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
  • Preparation method of lenalidomide for treating multiple myeloma
  • Preparation method of lenalidomide for treating multiple myeloma
  • Preparation method of lenalidomide for treating multiple myeloma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] A preparation method for lenalidomide for treating multiple myeloma, the preparation method comprising the following steps:

[0032] 1) 19.5g (100mmol) of methyl 2-methyl-3-nitrobenzoate, 14.1g (110mmol) of 3-amino-2,6-piperidinedione, 58.1g (500mmol) of tetramethylethylenediamine ), 48.8g (160mmol) of zinc bromide were added to the reaction vessel, 250ml of 1,4-dioxane was added and the temperature was raised to 90°C for a mixed reaction for 10 to 16 hours. After the reaction, cooled to room temperature and concentrated under reduced pressure , washed with water, and recrystallized (petroleum ether:dichloromethane=10:1) to obtain a white solid 3-(7-nitro-3-oxo-1H-isoindol-1-yl)piperidine-2,6- Diketone 26.1g, yield 90.1%, HPLC purity 99.32%; 1 HNMR (300MHz, DMSO-d 6 )δ:11.04(s,1H),8.47(d,1H),8.19(d,1H),7.86(t,1H),5.20-5.17(m,1H),4.94-4.82(m,2H),2.95 -2.88(m,1H),2.63-2.50(m,2H),2.05-2.01(m,1H).

[0033] 2) Add 10 g of 3-(7-amino-3-oxo-1H-isoindol-1-yl)piperidine-2,6-...

Embodiment 2

[0035] A preparation method for lenalidomide for treating multiple myeloma, the preparation method comprising the following steps:

[0036] 1) 19.5g (100mmol) of methyl 2-methyl-3-nitrobenzoate, 14.1g (110mmol) of 3-amino-2,6-piperidinedione, 46.5g (400mmol) of tetramethylethylenediamine ), zinc bromide 54.9g (180mmol) joins in the reaction container, adds 250ml toluene and heats up to 95 ℃ and carries out mixed reaction 10~16 hours, after reaction finishes, cools to room temperature, concentrates under reduced pressure, washes with water, recrystallizes (petroleum Ether: dichloromethane=10:1) to obtain 25.9 g of 3-(7-nitro-3-oxo-1H-isoindol-1-yl)piperidine-2,6-dione with a yield of 89.4 %, HPLC purity 99.62%;

[0037] 2) Add 10 g of 3-(7-amino-3-oxo-1H-isoindol-1-yl)piperidine-2,6-dione and 0.5 g of 5% palladium carbon to a high pressure with 18 ml of ethanol In the kettle, feed hydrogen (the pressure of feeding hydrogen is 0.5 MPa), and perform a reduction reaction at 50 °...

Embodiment 3

[0039] A preparation method of lenalidomide for the treatment of multiple myeloma, the preparation method comprising the following steps:

[0040] 1) 19.5 g (100 mmol) of methyl 2-methyl-3-nitrobenzoate, 15.4 g (120 mmol) of 3-amino-2,6-piperidinedione, 58.1 g (500 mmol) of tetramethylethylenediamine ), zinc bromide 45.8g (150mmol) are joined in the reaction vessel, add 250ml 1,4-dioxane and be warming up to 95 ℃ to carry out mixed reaction 10~16 hours, after the reaction finishes, be cooled to room temperature, concentrated under reduced pressure , washed with water, and recrystallized (petroleum ether:dichloromethane=10:1) to obtain 3-(7-nitro-3-oxo-1H-isoindol-1-yl)piperidine-2,6-dione 26.2g, yield 90.7%, HPLC purity 99.51%;

[0041] 2) 10 g of 3-(7-amino-3-oxo-1H-isoindol-1-yl) piperidine-2,6-dione and 0.3 g of 5% palladium on carbon were added to a high pressure containing 15 ml of ethanol. In the kettle, feed hydrogen (the pressure of feeding hydrogen is 0.35MPa), at 4...

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 drug synthesis technology and discloses a preparation method of lenalidomide for treating multiple myeloma. The preparation method comprises the following steps: firstly, carrying out hybrid reaction on 2-methyl-3-methyl 3-nitrobenzoate and 3-amino-2,6-dioxopiperidine in an organic solvent in the presence of tetramethylethylenediamine and zinc bromide, so as to obtain 3-(7-nitro-3-oxo-1H-isoindol-1-yl) piperidine-2,6-dione; secondly, carrying out catalytic hydrogenation reduction on 3-(7-nitro-3-oxo-1H-isoindol-1-yl) piperidine-2,6-dione, so as to obtain the lenalidomide. The preparation method of the lenalidomide, disclosed by the invention, has the advantages of mild conditions, simple reaction steps and environment friendliness, so that the preparation method is more suitable for industrial production.

Description

technical field [0001] The invention relates to drug synthesis technology, in particular to a preparation method of lenalidomide for treating multiple myeloma. Background technique [0002] Lenalidomide, the chemical name is 3-(7-amino-3-oxo-1H-isoindol-1-yl)piperidine-2,6-dione, which is mainly used to treat multiple myeloma and dysplastic syndrome subtype disease. Lenalidomide was developed by Celgene Biopharmaceutical Company of the United States. The application of lenalidomide in the treatment of multiple myeloma bone marrow and dysplastic syndrome subtype diseases has significantly improved the therapeutic effect of such diseases. The specific chemical structure of lenalidomide is as follows: [0003] [0004] In view of the good application value of lenalidomide, medical workers have carried out a lot of research on the preparation of lenalidomide and its intermediates, such as Fang Feng et al. in Chinese Journal of Medicine (2008,39 (12): 888-890) A preparatio...

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): C07D401/04A61P35/00
CPCC07D401/04
Inventor 董媛媛
Owner SHANGHAI WANXIANG PHARMA
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