Supercharge Your Innovation With Domain-Expert AI Agents!

Preparation method of cabozantinib nitrogen oxide impurity

A technology of nitrogen oxides and cabozantinib, which is applied in the field of preparation of cabozantinib nitrogen oxide impurities, which can solve the problems of long synthetic route steps, many potential impurities, and complex structural formula of cabozantinib

Inactive Publication Date: 2020-08-11
廊坊市泽康医药科技有限公司
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The structural formula of cabozantinib is relatively complex, and the steps of the synthetic route are long. This situation leads to many potential impurities in the API of cabozantinib. The synthesis of this series of impurity reference substances is of great significance to the quality research of cabozantinib

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 cabozantinib nitrogen oxide impurity
  • Preparation method of cabozantinib nitrogen oxide impurity
  • Preparation method of cabozantinib nitrogen oxide impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment Construction

[0023] The technical solutions of the present invention will be further described below through the accompanying drawings and embodiments.

[0024] The invention provides a method for preparing cabozantinib nitrogen oxide impurities, comprising the following steps:

[0025] S1. Preparation of intermediate 1: first mix cyclomalonic acid and ethyl acetate, when the temperature is lowered to less than 5°C, add triethylamine, control the temperature to less than 10°C, react for 1h, then drop the temperature when the temperature is less than 10°C Add thionyl chloride, react for 1 hour, add p-fluoroaniline when the temperature is less than 10°C, and react for 16 hours. PE / 1L TBME was beaten, filtered and dried to obtain intermediate 1. The reaction formula of intermediate 1 is as follows:

[0026]

[0027] Preparation of S2, 4-chloro-6,7-dimethoxyquinoline: 4-hydroxyl-6,7-dimethoxyquinoline, acetonitrile, phosphorus oxychloride are added to the reactor successively, and the temp...

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 a cabozantinib nitrogen oxide impurity. The method comprises the following steps: preparation of an intermediate 1, preparation of 4-chloro-6, 7-dimethoxyquinoline, preparation of an intermediate 2, and preparation of the cabozantinib nitrogen oxide impurity, wherein adding an organic solvent into a reactor at room temperature, stirring for 10 minutes, adding the intermediate 1, stirring for 20 minutes, adding the intermediate 2, reacting for 3 hours until 14% of the raw materials are left, heating to 35 DEG C for complete reaction, adding water,separating out a product, and carrying out suction filtration to obtain the cabozantinib nitrogen oxide impurity. By adopting the preparation method of the cabozantinib nitric oxide impurity, high-temperature and high-pressure reaction is avoided in the synthesis process, the synthesis method is mild and easy to operate, all steps are mild and controllable, the operation is simple, and the controllability is high.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to a method for preparing cabozantinib nitrogen oxide impurities. Background technique [0002] Cabozantinib was developed by Exelixis Biopharmaceutical Company of the United States. It is a multi-target broad-spectrum anticancer drug. The targets that can be inhibited include: MET, VEGFR1 / 2 / 3, ROS1, RET, AXL, NTRK, KIT, etc. At least 9. At present, cabozantinib has demonstrated good therapeutic effects in various solid tumors such as renal cancer, thyroid cancer, liver cancer, soft tissue sarcoma, non-small cell lung cancer, prostate cancer, breast cancer, ovarian cancer, and bowel cancer. The effect on the control of bone metastases is particularly prominent. Because of its broad effectiveness against a variety of cancers, cabozantinib is known as the "magic balm" among targeted drugs. [0003] The structural formula of cabozantinib is relatively complex, and the s...

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): C07D215/60
CPCC07D215/60
Inventor 杨卫民孙玉琴
Owner 廊坊市泽康医药科技有限公司
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com