Synthetic method of lapatinib

A technology of di-p-toluenesulfonic acid and lapatinib, which is applied in the direction of organic chemistry, can solve the problems of difficult control of the reaction process of transition intermediates, poor stability of iodide intermediates, and difficulty in industrial production, so as to achieve simple reaction operation Ease of operation, easy post-processing, and shortened reaction time

Inactive Publication Date: 2013-06-19
CHANGZHOU HONGCHUANG POLYMER SCI & TECH LTD
View PDF5 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] In this method, the reaction process of the transition intermediate is not easy to control, and the industrial productio

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
  • Synthetic method of lapatinib
  • Synthetic method of lapatinib
  • Synthetic method of lapatinib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Under the protection of nitrogen, transfer 2-furfural diethyl acetal (31.6g, 2.5eq) and 310mL dry ethylene glycol dimethyl ether into the flask, cool the system down to -40°C, and add n-butyl lithium in tetrahydrofuran (106mL, 2.2mol / L, 2.5eq) was added dropwise to the reaction system, maintained at -40~-50°C and stirred for 2.5~3h, then added dropwise 51.2mL of triisopropyl borate, then stirred at -60°C for 1h Then let the system warm up to room temperature naturally, slowly add 12.8mL glacial acetic acid dropwise, then stir for 30min, then add dropwise 15.5mL water. 126 mL of methanol, 25.9 mL of triethylamine, and then N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-iodo-4-quinazolinamine ( 37.5g, 1eq), 4.5g of 10% palladium carbon, and then the reaction system was heated to reflux temperature, and reacted for 14h. After the temperature of the reaction mixture was lowered to room temperature, it was filtered, the filter cake was washed with ethylene glycol dimethyl...

Embodiment 2

[0027]Under the protection of nitrogen, transfer 474g of 2-furfural diethyl acetal and 4500mL of dry tetrahydrofuran to the flask, cool the system to -40°C, and add a tetrahydrofuran solution (1590mL, 2.2mol / L) of n-butyllithium dropwise to In the reaction system, keep stirring at -40~-50°C for 2.5~3h, then add 768mL of triisopropyl borate dropwise, then stir at -60°C for 1h, let the system warm up to room temperature naturally, and slowly add 192mL of glacial acetic acid dropwise, Then stirred for 30min, and then added dropwise 78mL of water. Add 1890mL ethanol thereto, 388mL triethylamine, then add N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-iodo-4-quinazolinamine 562g, 68g of 10% palladium carbon, and then the reaction system was heated to reflux for 14h. After the temperature of the reaction mixture was lowered to room temperature, it was filtered, the filter cake was washed with tetrahydrofuran, and the filtrates were combined. Add 120g of triethylamine to the filt...

Embodiment 3

[0029] Under the protection of nitrogen, 950 g of 2-furfural diethyl acetal and 9000 mL of dry tetrahydrofuran were transferred to the flask, the temperature of the system was lowered to -40 ° C, and the tetrahydrofuran solution (3180 mL, 2.2 mol / L) of n-butyllithium was added dropwise to In the reaction system, keep stirring at -40~-50°C for 2.5~3h, then add 1536mL of triisopropyl borate dropwise, then stir at -60°C for 1h, let the system warm up to room temperature naturally, and slowly add 384mL of glacial acetic acid dropwise, Then stirred for 30min, and then added dropwise 156mL of water. Add 3780mL ethanol thereto, 776mL triethylamine, then add N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]-6-iodo-4-quinazolinamine 1124g, 134 g of 10% palladium on carbon, and then the reaction system was heated to reflux temperature for 14 hours of reaction. After the temperature of the reaction mixture was lowered to room temperature, it was filtered, the filter cake was washed with te...

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 synthetic method of lapatinib. 2-furaldehyde diethyl acetal, N-[3-Cl-4-[(3- fluorobenzoic) methoxy] phenyl]-6-I-4-quinazoline amine and the like serve as raw material, are subjected to three steps of reaction to obtain the lapatinib. The method implements one-pot reaction and is easy to operate, the reaction conversion rate reaches up to 70%, and the purity reaches 98%. Involved solvents are small in toxicity, high in recycling rate and few in three wastes. The involved intermediates are good in crude product purity, can be directly used for latter reaction without the need for aftertreatment and purification, and are suitable for industrial magnification production.

Description

technical field [0001] The invention relates to a synthetic method of lapatinib. Background technique [0002] Lapatinib di-p-toluenesulfonate (Iapatinib), the scientific name is N-(3-chloro-4-((3-fluorophenyl)methoxy)phenyl)-6-(5-(((2 -(methylsulfonyl)ethyl)amino)methyl)-2-furyl)-4-quinazolinamine di-p-toluenesulfonate, a new class of therapeutics targeting HER2, March 2007 Approved in the United States for the treatment of advanced breast cancer patients with HER2 overexpression, the particularity of lapatinib is that patients who have received other chemotherapy drugs will not develop cross-resistance to it, and can effectively slow down Disease progression in breast cancer. Many other clinical trials are currently underway to study lapatinib in other cancers. The molecular structural formula of lapatinib is as follows: [0003] [0004] As a new drug targeting HER2, lapatinib can be effective in patients after Herceptin fails to target HER2 therapy, and there are ...

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
IPC IPC(8): C07D405/04
Inventor 庄韦岳邦毅陈强
Owner CHANGZHOU HONGCHUANG POLYMER SCI & TECH LTD
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