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

Method for synthesizing Nexavar

A synthesis method and compound technology, which can be applied in the fields of drug combination, antitumor drugs, organic chemistry, etc., can solve the problems of poor economy, low yield, and low compound VI synthesis yield, avoid the use of phosgene, and improve safety. and operability, improved product purity and environmental compatibility

Inactive Publication Date: 2010-03-17
SHANGHAI PUYI CHEM CO LTD
View PDF6 Cites 16 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The main disadvantage of using compound VI is that the synthetic yield of compound VI is very low
We can only obtain compound VI with a very low yield by using the synthetic method in the literature, which leads to only 20-30% of the synthetic yield of this process. At the same time, the purification of the product also needs the method of column chromatography separation, so the economy of this process is too high. Difference

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 Nexavar
  • Method for synthesizing Nexavar
  • Method for synthesizing Nexavar

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0042] 1.1 Preparation of phenyl (4-chloro-3-trifluoromethyl-phenyl)carbamate

[0043] Add compound IV (4-chloro-3-trifluoromethyl-benzene, Gaoyou Guangming Chemical Factory, chemically pure) 5g in the there-necked flask, add 50ml of dichloromethane (Shanghai Chemical Reagent Co., Ltd., chemically pure) and stir to dissolve completely, Add 4 g of pyridine (Shanghai Chemical Reagent Co., Ltd., chemically pure). A mixed solution of 10 ml of dichloromethane and 4.2 g of phenyl chloroformate (Shanghai Chemical Reagent Co., Ltd., chemically pure) was added dropwise at room temperature, and reacted for half an hour. TLC (PE: EA = 3: 1) showed that the reaction of the raw material was complete, washed once with 1N hydrochloric acid, washed three times with water, dried, filtered, weighed 7.6 g after drying, and the molar yield was 94%.

[0044] 1 H NMR (CDCl 3 , 500MHz): δ=7.1(s, 1H), 7.2(d, J=7Hz, 2H), 7.3(m, 1H), 7.4(m, 2H), 7.5(d, J=8Hz, 1H), 7.6 (d, J=8Hz, 1H), 7.8 (s, 1H). ...

Embodiment 2

[0059] 2.1 Preparation of 4-nitrophenyl (4-chloro-3-trifluoromethyl-phenyl)carbamate

[0060] Add compound IV (4-chloro-3-trifluoromethyl-benzene, Gaoyou Guangming Chemical Factory, chemically pure) 5g in the there-necked flask, add 50ml of dichloromethane (Shanghai Chemical Reagent Co., Ltd., chemically pure) and stir to dissolve completely, Add 4 g of pyridine (Shanghai Chemical Reagent Co., Ltd., chemically pure). A mixed solution of 10 ml of dichloromethane and 5.1 g of p-nitrophenyl chloroformate (Shanghai Chemical Reagent Co., Ltd., chemically pure) was added dropwise at room temperature, and reacted for half an hour. TLC (PE: EA = 3: 1) showed that the reaction of the raw material was complete, washed once with 1N hydrochloric acid, washed three times with water, dried, filtered, weighed 8.4 g after drying, and the molar yield was 92%.

[0061] 1 H NMR (CDCl 3 , 500MHz): δ=7.1(d, J=7Hz, 1H), 7.2(dd, J=7Hz, J=3Hz, 1H), 7.3(d, J=7Hz, 2H), 7.7(d, J=3Hz , 1H), 7.8 (s, 1...

Embodiment 3

[0076] 3.1 Preparation of 2-nitrophenyl (4-chloro-3-trifluoromethyl-phenyl)carbamate

[0077] Add compound IV (4-chloro-3-trifluoromethyl-benzene, Gaoyou Guangming Chemical Factory, chemically pure) 5g in the there-necked flask, add 50ml of dichloromethane (Shanghai Chemical Reagent Co., Ltd., chemically pure) and stir to dissolve completely, Add 4 g of pyridine (Shanghai Chemical Reagent Co., Ltd., chemically pure). A mixed solution of 10 ml of dichloromethane and 5.1 g of o-nitrophenyl chloroformate (Shanghai Chemical Reagent Co., Ltd., chemically pure) was added dropwise at room temperature, and reacted for half an hour. TLC (PE: EA = 3: 1) showed that the reaction of the raw material was complete, washed once with 1N hydrochloric acid, washed three times with water, dried, filtered, weighed 8.4 g after drying, and the molar yield was 92%.

[0078] 1 H NMR (CDCl 3 , 500MHz): δ=7.1(d, J=7Hz, 1H), 7.2(dd, J=7Hz, J=3Hz, 1H), 7.3(dd, J=7Hz, J=3Hz, 1H), 7.3(m , 1H), 7.6 (m, ...

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 method for synthesizing Nexavar. The method comprises the following steps: a, dissolving a compound II and a compound III in an organic solvent inert to the compound III and adding appropriate base; b, performing reaction at a reaction temperature between 40 and 150 DEG C so as to generate a crude Nexavar product; and c, performing conventional post-treatment on the crudeproduct, wherein R is hydrogen, methyl, nitro or chlorine; the nitro is on site 4; the methyl or the chlorine is on site 2, 3 or 4; and the compound III is prepared through the reaction of a compoundIV and phenyl chloroformate or the phenyl chloroformate containing substituents on benzene rings in an organic reaction solvent inert to chloroformate at a temperature between 10 DEG C below zero and50 DEG C. The method has the advantages of applying to the preparation of Nexavar on an industrial scale, meeting standards in pharmaceutical industrial production, improving the purity and environmental compatibility of products and improving operability, safety and yield.

Description

technical field [0001] The present invention relates to the technical field of compound preparation, in particular to the technical field of Sorafenib preparation, and more specifically, to a synthetic method of Sorafenib. Background technique [0002] Compound 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-N-methylpyridine-2-carboxamide, also known as Rafenib, first recorded in the patent WO0042012, the molecular formula is C 21 h 16 CIF 3 N 4 o 3 , its structural formula is shown in formula I, and its molecular weight is 464.83. The report disclosed in patent WO0042012 shows that compound I is an inhibitor of Raf kinase and can be used for treating diseases such as cancer. [0003] [0004] Patents WO0042012, WO2006034796, WO2006089150, WO2007059154, WO2007053574, US7235576 and literature (Bankston et al., Organic Process Research & Development; 2002, 6, 777-781) describe methods for the preparation of compound I, which can be illustrate...

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): C07D213/81A61P43/00A61P35/00
Inventor 王博罗宇
Owner SHANGHAI PUYI 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