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

Preparation method of pelitinib

A technology for pelitinib and preparation steps, which is applied in the field of pelitinib preparation, can solve the problems of limiting the industrialization prospect of the process route, high temperature and long-term reflux, etc., and achieves the effects of promoting development, easy availability of raw materials, and simple process

Inactive Publication Date: 2013-09-04
SUZHOU MIRACPHARMA TECH +1
View PDF6 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This synthetic route has a classic reaction and a stable process, but the cyclization reaction requires high temperature and long-term reflux, especially the chlorination reaction requires the use of highly toxic substances such as phosphorus oxychloride that have an impact on the environment, thus limiting the industrialization of this process route prospect

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 pelitinib
  • Preparation method of pelitinib
  • Preparation method of pelitinib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Add 6-[(E)-4-(dimethylamino)-2-butenamido]-7-ethoxy-4-amino-3-quinolinecarbonitrile (II) into the three-neck reaction flask (3.4g, 10mmol), triethylamine (1.5g, 15mmol) and methanol 25mL, warm up to 50-55°C, stir until the system is uniformly dissolved. A methanol solution of 3-chloro-4-fluorobenzaldehyde (III) (1.9 g, 12 mmol) was slowly added dropwise to the reaction liquid, and the drop was completed in about 1 hour. Keep this temperature and continue to react for 3 hours, and TLC detects that the reaction is complete. The temperature was lowered to 0-5°C, and sodium borohydride (1.9 g, 50 mmol) was added in portions, and the addition was completed in about 1 hour. Keep the room temperature to continue the reaction for 2 hours, and TLC detects that the reaction is complete. The reaction was quenched by adding dilute hydrochloric acid. Concentrate under reduced pressure to one-third of the total volume, cool down and crystallize, and recrystallize the crude product...

Embodiment 2

[0030] Under dryness and a nitrogen atmosphere, 3-ethoxy-4-[(E)-4-(dimethylamino)-2-butenamido]aniline (IIa) (2.6g, 10mmol), triethyl orthoformate (IIb) (1.63g, 11mmol) and malononitrile (IIc) (0.80g, 12mmol) and absolute ethanol 25mL, heated to reflux for 3 hours. After cooling and crystallization, the crude product was dissolved in 25 mL of N,N-dimethylformamide, then aluminum trichloride (5.32 g, 40 mmol) was added, heated to 140° C., and kept for 2 hours for reaction. After cooling, the reaction system was poured into ice water, and a solid precipitated out. Filtration, the filtrate was extracted with dichloromethane, concentrated, and the crude product was recrystallized from ethanol to obtain a white solid 6-[(E)-4-(dimethylamino)-2-butenamido]-7-ethoxy-4 -Amino-3-quinolinecarbonitrile (II) 2.9g, yield 85.5%.

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 preparation method of pelitinib (I). The preparation method includes steps as follows: 6-[(E)-4-(dimethylamino)-2-butene acylamino]-7-ethoxy-4-amino-3-quinoline formonitrile (II) and 3-chlorine-4-fluorobenzaldehyde (III) perform condensation and reduction reaction, and the pelitinib (I) is obtained. According to the preparation method, raw materials are easy to obtain, the process is simple and concise, and the method is economical, environment-friendly and suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis route design and preparation of raw materials and intermediates, and in particular relates to a preparation method of pelitinib. Background technique [0002] Pelitinib is a reversible epidermal growth factor receptor (EGFR) inhibitor developed by Wyeth Pharmaceuticals, a subsidiary of Pfizer in the United States. It has completed phase II clinical research and can be used clinically for treatment Advanced non-small cell lung cancer, colorectal cancer, etc. [0003] The chemical name of Pellitinib is: (2E)-N-[4-[(3-chloro-4-fluorophenyl)amino]-3-cyano-7-ethoxy-6-quinolinyl] -4-(dimethylamino)-2-butenamide, with the structural formula: [0004] [0005] World Patent No. WO2004 / 032909, No. WO2004 / 066919, U.S. Patent No. US2005 / 0026933, No. US2005 / 065181, No. US2005 / 0059678, "Journal of Medicinal Chemistry" 2003 Volume 46 Page 49 and " The 125th page of volume 44 of China Pharmaceutic...

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): C07D215/54
Inventor 许学农
Owner SUZHOU MIRACPHARMA TECH
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