Synthesis method of anti-tumor targeted therapeutic drug tivozanib

A synthesis method and a technology for targeted therapy, which are applied in the synthesis process of compounds and the synthesis route of the anti-tumor targeted therapy drug tivozanib, can solve the problems of few research reports on the synthesis process of the drug, and achieve low cost, high yield, The effect of cheap and readily available synthetic raw materials

Active Publication Date: 2012-07-04
WUHAN MAIDESEN MEDICAL TECH
View PDF3 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Since the drug is currently in the clinical research stage and has not yet been marketed, there are few reports on the synthesis process of the drug at home and abroad.

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
  • Synthesis method of anti-tumor targeted therapeutic drug tivozanib
  • Synthesis method of anti-tumor targeted therapeutic drug tivozanib
  • Synthesis method of anti-tumor targeted therapeutic drug tivozanib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example one 3,4-dimethoxyacetophenone (compound 1a )Synthesis

[0034]

[0035] In a 250ml three-necked flask, add 80ml of chloroform and 22.0g (0.16mol) of anhydrous aluminum trichloride, and dropwise add 10.2g (0.13mol) of acetyl chloride and 13.8g (0.1mol) of phthalate in sequence at room temperature. After completion, stir at room temperature until the end of the reaction (GLC tracking). The above reaction solution was poured into 500ml of dilute hydrochloric acid, stirred, the organic phase was separated, the aqueous phase was extracted with chloroform, the organic phases were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 15.0g of white powder compound 1a (C 10 H 12 O 3 ), m.p. 48-52°C, yield 83%. IR (cm -1 ): 1673, 1585, 1515, 1418; 1 H-NMR (CDCl 3 / ppm): δ 2.55 (s, 3H), 3.73 (s, 3H), 3.73 (s, 3H), 6.77 (s, 1H), 7.26 (s, 1H), 7.31 (s, 1H).

Embodiment 2

[0036] Example two 3,4-dimethoxy-6-nitroacetophenone (compound 1b )Synthesis

[0037]

[0038] In a 500ml three-necked bottle, add 100ml formic acid and 18g (0.1mol) of the compound 1a , 60ml of concentrated nitric acid was added dropwise below 10°C, the dropping was completed, the temperature was raised to 60-70°C, and stirred for 30min. The above reaction solution was poured into a 500ml ice-water bath, stirred and filtered to obtain 36.9g of light yellow powder compound 1b (C 10 H 11 NO 5 ), m.p. 135-137°C, 82% yield. 1 H-NMR (CDCl 3 / ppm): δ 2.50 (s, 3H), 3.97 (s, 3H), 3.99 (s, 3H), 6.76 (s, 1H), 7.62 (s, 1H).

Embodiment 3

[0039] Example three 2-amino-4,5-dimethoxyacetophenone (compound 1c )Synthesis

[0040]

[0041] In a 250ml three-necked flask, add 36ml water and 7g (0.125mol) reduced iron powder, heat up, reflux for 1h, slowly add 5.6g (0.025mol) compound 1b , stirred for 3h, suction filtered, and the filtrate was cooled to obtain 7g of yellow powder compound 1c (C 10 H 13 NO 3 ), m.p. 106-108°C, yield 96%. 1 H-NMR (CDCl 3 / ppm): δ 2.56 (s, 3H), 3.84 (s, 3H), 3.88 (s, 3H), 6.10 (s, 1H), 7.11 (s, 1H).

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 synthesis route of an anti-tumor targeted therapeutic drug tivozanib, which comprises the following steps that: o-dimethoxy benzene used as a starting material is subjected to Friedel-Crafts acylation, nitration, reduction, addition elimination, chlorination, and condensation and substitution reactions to synthesize the tivozanib. The synthesis method provided by the invention has the advantages that: the synthetic raw materials are cheap and easy to obtain, the reaction conditions are mild, the process is stable, the cost is low, the yield is high and the like, and therefore, the method provided by the invention is suitable for industrial production of tivozanib.

Description

technical field [0001] The invention relates to a synthesis process of a compound, in particular to a synthesis route of an anti-tumor targeted therapy drug tivozanib, which belongs to the technical field of chemical synthesis. Background technique [0002] Tivozanib, also known as AV-951, chemically named N-{2-chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]phenyl}-N'-(5- Methyl-3-isoxazolyl)urea. [0003] Structural formula: [0004] [0005] Molecular formula: C 22 h 19 ClN 4 o 5 [0006] Molecular weight: 454.86 [0007] Tivozanib is an anti-tumor targeted therapy drug. It is a multi-target anti-angiogenesis inhibitor anti-cancer drug. It is mainly used for the treatment of renal cancer. The point is vascular endothelial growth factor VEGFR1, 2, 3. By inhibiting these three vascular endothelial growth factor receptors, it can play a role in the treatment of patients with renal cell tumors. After taking tivozanib, the average survival time of patients is 11.8 months wi...

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): C07D413/12
Inventor 刘明星胡利修吴建宏张志祥刘军安
Owner WUHAN MAIDESEN MEDICAL TECH
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