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

Method for synthesizing lenalidomide

A technology of lenalidomide and a synthesis method, applied in the field of synthesis of lenalidomide, can solve the problems of expensive raw materials, unsuitable for industrial production, difficult purification, etc., achieves improvement of quality and yield, and realizes green production and technology The effect of easy availability of raw materials

Inactive Publication Date: 2020-01-03
TIANJIN RUILING CHEM CO LTD
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] According to publicly reported data, there are many preparation methods for lenalidomide. Patent CN101665484 utilizes 2-bromomethyl-3-nitrobenzoic acid methyl ester and L-glutamine methyl ester to react, and through cyclization reaction, Synthesis of lenalidomide through 6-step reactions such as racemization reaction, but this method has low yield, difficult purification and expensive raw materials
There are also related literature reports to prepare by reacting 2-bromomethyl-3-nitrobenzoic acid methyl ester and L-glutamine, but this method still has long steps, difficult post-processing, complicated operation, and is not suitable for industrial production
[0004] Due to many problems in the traditional process, it does not meet the current national requirements for green chemistry, which affects the healthy and sustainable development of such products

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 synthesizing lenalidomide
  • Method for synthesizing lenalidomide
  • Method for synthesizing lenalidomide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Embodiment 1: (1) the preparation of 2-bromomethyl-3-nitrobenzoic acid methyl ester: add 19.5g2-methyl-3-nitrobenzoic acid methyl ester in 200mL ethyl acetate ethyl ester, 18.6g N - 0.24 g of bromosuccinimide and benzoyl peroxide, the mixed solution was stirred at 65° C. for 1 hour, and then cooled to room temperature. 200 mL of water was added, the organic layer was separated and evaporated under vacuum to give a solid, which was recrystallized from petroleum ether to give the product. Pale yellow solid, 26.5g, yield 97%. The product was detected: m.p.: 69-70°C; 1HNMR (400MHz, CDCl3) δ8.11(d, J=7.8Hz, 1H), 7.96(d, J=7.9Hz, 1H), 7.55(t, J=8.0 Hz, 1H), 5.16(s, 2H), 4.00(s, 3H).

[0025] (2) Preparation of 3-(4-nitro-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione: 10.9g 2-(bromomethyl )-Methyl 3-nitrobenzoate, 6.6g of 3-aminopiperidine-2,6-dione hydrochloride, and 5.96g of triethylamine were stirred at 85°C for 45 minutes under nitrogen protection. After the reac...

Embodiment 2

[0027] Embodiment 2: (1) Preparation of 2-bromomethyl-3-nitrobenzoic acid methyl ester: in 2L 1,2-ethylene dichloride, add 195.3g 2-methyl-3-nitrobenzoic acid methyl Esters, 186.1 g of N-bromosuccinimide and 2.46 g of benzoyl peroxide, the mixed solution was stirred at 85° C. for 1 hour, and then cooled to room temperature. 2 L of water was added, the organic layer was separated and evaporated under vacuum to give a solid which was recrystallized from petroleum ether to give the product. Pale yellow solid, 268.3g, yield 98%. The product was detected: m.p.: 68-70°C; 1H NMR (400MHz, CDCl3) δ8.10(d, J=7.8Hz, 1H), 7.94(d, J=7.9Hz, 1H), 7.55(t, J= 8.0Hz, 1H), 5.16(s, 2H), 4.00(s, 3H).

[0028] (2) Preparation of 3-(4-nitro-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione: 108.8g 2-(bromomethyl )-Methyl 3-nitrobenzoate, 66.3g of 3-aminopiperidine-2,6-dione hydrochloride, and 596.3g of sodium carbonate were stirred at 100°C for 45 minutes under nitrogen protection. After the r...

Embodiment 3

[0030] Example 3: Step (1) in Example 3 is the same as step (3), the only difference is that 3-(4-nitro-1-oxo-1,3-dihydroiso Preparation of indol-2-yl)piperidine-2,6-dione: 4.7g methyl 2-(bromomethyl)-3-nitrobenzoate, 2.9g 3-aminopiperidine-2,6-dione A mixture of ketone hydrochloride and 2.5 g of triethylamine was stirred at 60° C. for 45 minutes under nitrogen protection. After the reaction was complete, the mixture was cooled to room temperature, 40 mL of ethanol was added, and stirred for 5 minutes. The precipitate was then collected by filtration and dried to yield the product. Off-white solid, 5.2g, yield 89%. The product was detected: m.p.: 274-275°C; 1H NMR (400MHz, DMSO) δ11.06(s, 1H), 8.48(d, J=8.0Hz, 1H), 8.19(d, J=7.3Hz, 1H) ,7.87(t,J=7.8Hz,1H),5.16(dd,J=13.0,4.8Hz,1H),4.87(dd,J=46.3,19.4Hz,2H),2.98–2.83(m,1H), 2.65–2.53(m,2H), 2.07–2.00(m,1H).

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 belongs to the field of chemical synthesis, and particularly relates to a method for synthesizing lenalidomide. The method adopts three-step polymerization, and specifically comprises: (1) carrying out a bromination reaction on 2-methyl-3-nitromethyl benzoate as a starting raw material and a bromination reagent to generate a compound 1 2-bromomethyl-3-nitromethyl benzoate; (2) performing cyclization on the compound 1 and 3-aminopiperidine-2,6-dione hydrochloride under a solvent-free condition to generate a compound 2 3-(4-nitro-1-oxo-1,3-dihydroisoindole-2-yl)piperidine-2,6-dione; and (3) reducing the compound 2 with a reducing agent to obtain lenalidomide. According to the invention, the method is a novel preparation process method of lenalidomide, and has advantages of easily available process raw materials, short steps, simple and convenient operation, environmental friendliness, implementation value of industrial production, and social and economic benefits.

Description

technical field [0001] The invention belongs to the field of chemical synthesis, and in particular relates to a synthesis method of lenalidomide. Background technique [0002] Lenalidomide, brand name Revlimid, chemical name: 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)piperidine-2,6-dione , is an analogue of thalidomide, developed by Celgen, commonly used in the treatment of fatal blood diseases and cancer. Lenalidomide has a wide range of immunomodulatory effects, such as up-regulating the cytokine IL-2, thereby stimulating the production of T cells; inhibiting the production of tumor necrosis factor TNF-α, and enhancing the toxicity of natural killer cells. In early 2006, it was approved by the U.S. FDA for the treatment of myelodysplastic syndrome (MDS), and it was listed for the first time; lenalidomide is the only effective drug for the treatment of MDS, and clinical results found that 64% of MDS patients did not need to be treated with lenalidomide. Treat with blood t...

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): C07D401/04
CPCC07D401/04
Inventor 谢志强钟凯凯卢博为卢俊瑞张俊杰李有鸿黄爱昊
Owner TIANJIN RUILING CHEM CO LTD
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