Supercharge Your Innovation With Domain-Expert AI Agents!

Dasatinib preparation method

A technology of dasatinib and quantitative ratio, which is applied in the field of drug synthesis, can solve the problems of long synthetic routes, impure intermediate products, and large environmental pollution, and achieve the effects of increased yield, short reaction time, and no environmental pollution

Inactive Publication Date: 2019-06-14
SHANDONG LUOXIN PARMACEUTICAL GROUP STOCK CO LTD +2
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0023] This synthetic route is shorter, is a kind of suitable synthetic train of thought, but there is following shortcoming in this method: the first step reaction uses the large vinyl ethyl ether of danger to make starting material and trichloroacetyl chloride reaction, synthetic ( E)-3-ethoxyacryloyl chloride is highly volatile and difficult to preserve; the second step is to decarboxylate at high temperature. Under this condition, the second step product 3-ethoxyacryloyl chloride is easy to polymerize, resulting in a reduction in yield 1. The intermediate product is impure and needs to be purified by vacuum distillation, and the energy consumption has higher requirements on the equipment; in addition, the third and fourth steps use solvent tetrahydrofuran and dioxane respectively, and the cost is also high, and the fourth step A large amount of NBS is used in the first step, the cost is greatly increased, and the NBS reaction must be carried out at low temperature, and the conditions are harsh. In addition, the workload of post-processing is also increased.
[0026] This method improves the synthesis of 3-ethoxyacryloyl chloride, but the synthesis route becomes longer, the operation is cumbersome, and chlorinated reagents that are volatile and pollute the environment are used in the reaction process

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
  • Dasatinib preparation method
  • Dasatinib preparation method
  • Dasatinib preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: Synthesis of compound 3

[0044] Dissolve 30mmol of ethyl 3-oxopropionate and 37.5mmol of sodium methoxide in 80mL of tetrahydrofuran. After stirring at room temperature for 10 minutes, add 27mmol of 2-chloro-6-methylaniline, heat and reflux for 1 hour. After the reaction is over, cool to room temperature. Add 60mL of tetrahydrofuran with 81mmol of copper bromide dissolved in it, heat to reflux for 2h, filter while hot, wash the filter cake with 50mL of hot tetrahydrofuran, combine the filtrate with the washing liquid, wash with water until neutral, distill under reduced pressure to remove the solvent, and pour the residue into Stir in 50 mL of ice water for 0.5 h, filter under reduced pressure, wash the filter cake with ice water, and dry to obtain 7.19 g of compound 3 with a yield of 91.60% and a purity of 99.92%.

Embodiment 2

[0045] Example 2: Synthesis of Compound 3

[0046] Dissolve 30mmol of ethyl 3-oxopropionate and 39mmol of sodium methoxide in 80mL of tetrahydrofuran. After stirring for 10min at room temperature, add 30mmol of 2-chloro-6-methylaniline and heat to reflux for 1h. After the reaction, cool to room temperature and add 60mL of tetrahydrofuran with 84mmol of copper bromide dissolved in it, heated to reflux for 2h, filtered while hot, the filter cake was washed with 50mL of hot tetrahydrofuran, the filtrate was combined with the washing liquid, washed with water until neutral, the solvent was distilled off under reduced pressure, and the residue was poured into 50mL The mixture was stirred in ice water for 0.5 h, filtered under reduced pressure, and the filter cake was washed with ice water and dried to obtain 7.89 g of compound 3 with a yield of 90.43% and a purity of 99.90%.

Embodiment 3

[0047] Example 3: Synthesis of Compound 3

[0048] Dissolve 30mmol of ethyl 3-oxopropionate and 36mmol of sodium methoxide in 80mL of tetrahydrofuran. After stirring at room temperature for 10 minutes, add 24mmol of 2-chloro-6-methylaniline. The temperature is heated to reflux for 1 hour. After the reaction is over, it is cooled to room temperature and added 60mL of tetrahydrofuran with 78mmol of copper bromide dissolved in it, heated to reflux for 2h, filtered while hot, the filter cake was washed with 50mL of hot tetrahydrofuran, the filtrate was combined with the washing liquid, washed with water until neutral, the solvent was distilled off under reduced pressure, and the residue was poured into 50mL Stir in ice water for 0.5 h, filter under reduced pressure, wash the filter cake with ice water, and dry to obtain 5.99 g of compound 3 with a yield of 85.72% and a purity of 99.82%.

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 dasatinib preparation method which comprises the following steps: 3-oxo-propionic acid ethyl ester is reacted with 2-chloro-6-methylaniline under an alkaline condition, anda solution dissolved with copper bromide is added to react to obtain a compound 3; the compound 3 is reacted with thiourea to obtain 2-amino-N-(2-chloro-6-methylphenyl) thiazole-5-formamide; and 4, under the conditions of an alkali, a catalytic system and an organic solvent, 4,6-dichloro-2-methylpyrimidine is successively reacted with N-hydroxyethyl piperazine and the 2-amino-N-(2-chloro-6-methylphenyl) thiazole-5-formamide to prepare the compound 1, namely dasatinib. The method disclosed by the invention has the advantages of mild conditions, simple steps, short reaction time, high speed, environmental friendliness and high yield, and is suitable for industrial production.

Description

Technical field [0001] The invention relates to the field of drug synthesis, in particular to a preparation method of dasatinib. Background technique [0002] Dasatinib (Dasatinib, trade name Sprycel), chemical name is N-(2-chloro-6-methylphenyl)-2-[6-[4-(2-hydroxyethyl)-1-piper Azinyl]-2-Methyl-4-pyrimidinyl]amino-5-thiazolcarboxamide is an oral tyrosine kinase inhibitor developed by Bristol-Myers Squibb. The drug was approved by the FDA in June 2006 for the treatment of chronic myelogenous leukemia, and it can also treat Philadelphia chromosome-positive acute lymphoblastic leukemia. This product has an inhibitory effect on a variety of mutants of Bcr-Ab1 kinase, and the inhibitory strength is much higher than that of Imatinib, and no drug resistance has been found. Its structural formula is as follows: [0003] [0004] Regarding the synthesis of dasatinib, there are many reports in domestic and foreign literature, most of which are the synthesis of intermediate 2-amino-N-(2-c...

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): C07D417/12
Inventor 高红军任庆伟张庆东
Owner SHANDONG LUOXIN PARMACEUTICAL GROUP STOCK CO LTD
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