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

A kind of synthetic method of vemodinil

A technology of vemodinil and a synthesis method, which is applied in the synthesis field of vemodinil, can solve the problems of difficulty in obtaining raw materials, price, harsh reaction conditions, excessively long reaction steps, etc., and achieves a small amount of a reducing agent, a short synthesis route, Environmentally friendly effect

Active Publication Date: 2019-08-02
武汉博诚恒瑞医药科技有限公司
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The synthetic method disclosed in CN102731373A, as shown in synthetic route 2, has the following disadvantages: the price of p-chlorobenzoic acid as a raw material is high, and active diphenylphosphoryl azide is required for rearrangement, which is dangerous when used Sexuality, and expensive, resulting in high production costs of vemodini
[0009] The synthetic method disclosed in WO2006028958, as shown in synthetic route 3, the raw materials used in this method are difficult to obtain and expensive; benzoyl is used for protection, and high temperature and strong alkaline conditions are required for deprotection; the reaction steps are too long and the reaction conditions Harsh, resulting in extremely high production costs

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 kind of synthetic method of vemodinil
  • A kind of synthetic method of vemodinil
  • A kind of synthetic method of vemodinil

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0028] The present invention will be described in detail below through examples.

[0029] 1. Synthesis of Intermediate 2

[0030]

[0031] Add 2-chloro-5-nitrophenylboronic acid (0.201g, 1mmol), potassium carbonate (0.138g, 1mmol, 1eq), palladium acetate (0.0112g, 0.05mmol, 5mol%), isopropanol ( In a mixed solvent of 5mL) and water (5mL), after the solid is dissolved, add 2-bromopyridine (0.174g, 1.1mmol, 1.1eq) dropwise under stirring conditions, react at 25℃ for 3h, and extract with ethyl acetate Three times, the obtained organic phases were combined together, added with silica gel and spin-dried, packed in the column by dry method, and passed through the column with petroleum ether: ethyl acetate (v:v=1:1) to obtain the product intermediate 2-(2-chloro-5) -Nitrophenyl)pyridine (2) 0.219g, yield 96%.

[0032] 2. Synthesis of Intermediate 3

[0033]

[0034] Add intermediate 2-(2-chloro-5-nitrophenyl)pyridine (2) (0.114g, 0.5mmol), reducing agent Pd / C (5%Pd) (0.020g), organic base ...

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 synthesis method of vismodegib. The method comprises the following reactions: firstly, enabling 2-chloro-5-nitrophenyl boronic acid and 2-bromopyridine to make a coupled reaction to generate an intermediate 2-(2-chloro-5-nitro) phenylpyridine; reducing nitro in the 2-(2-chloro-5-nitro) phenylpyridine to amino so as to obtain 2-(2-chloro-5-amino) phenylpyridine; finally, enabling the 2-(2-chloro-5-amino) phenylpyridine and 2-chloro-4-methyl sulfuryl benzaldehyde to make a catalytic reaction to generate the vismodegib. The synthesis method is low in price of raw materials, easy in raw material obtaining, simple and convenient to operate and less in consumption of a catalyst; the reaction product is high in yield, reaction conditions are mild, and aftertreatment is simple in technology and mainly adopts column separation, so that industrial mass production can be realized.

Description

Technical field [0001] The invention relates to a synthesis method of vilmodinil. Background technique [0002] Vismodegib (Vismodegib), trade name Erivedge, chemical name 2-chloro-N-(4-chloro-3-(pyridin-2-yl)phenyl)-4-(methylsulfonyl)benzyl Amide, approved by the US Food and Drug Administration (FDA) in 2012, is used as a small molecule targeted inhibitor of the Hedgehog pathway for the treatment of base cell carcinoma. Vermodinil can effectively inhibit the Smoothened oncoprotein of the Hedgehog pathway, and has good solubility, free rate and clinical effects. At present, there are three main synthesis processes reported in the literature for vermodinil: [0003] The synthesis method disclosed in WO2009126863 is shown in synthesis route 1. Although the route of this method is short, the raw material cost is high. In addition, the preparation process of pyridine-2-zinc (II)-chloride requires the use of flammable and explosive n-butyl lithium, which is difficult to achieve indus...

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): C07D213/40
CPCC07D213/40
Inventor 张方林张雪琼
Owner 武汉博诚恒瑞医药科技有限公司
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