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

A kind of preparation method of antithrombotic drug

A compound and hydrate technology, which is applied in drug combination, blood diseases, organic chemistry, etc., can solve the problems affecting the purity of compounds, impurity is not easy to remove, and affects the synthesis of compounds, so as to reduce the phenomenon of reaction fuming, curing phenomenon disappears, Conducive to the effect of industrial production

Active Publication Date: 2019-06-18
JIANGSU VCARE PHARMATECH
View PDF4 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In the existing process for preparing the compound, there will be a risk of solidification, which will affect the synthesis of the compound, cause waste of resources, and be unfavorable for industrial production; at the same time, during the preparation process, the following impurities (1) will also be produced, the impurity Stubbornness is not easy to remove, seriously affecting the purity of the compound

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
  • A kind of preparation method of antithrombotic drug
  • A kind of preparation method of antithrombotic drug
  • A kind of preparation method of antithrombotic drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030]

[0031] Steps:

[0032] Add 279.40g of compound C and 1.4L of dichloromethane I into kettle 1, and add 120.42g of triethylamine after stirring; g compound 1 and 5L dichloromethane, stir well and add 514.67g methanesulfonic acid; kettle 2 is heated to 25±5°C and stirred for reaction; kettle 1 is reacted for 7 hours, kettle 2 is reacted for 2 hours; kettle 2 is soaked in triethylamine And, add the solution in kettle 2 to kettle 1, the heat release is not obvious; stir and react at 25±5°C for 20 hours; add 7L water to the system, stir for 1 hour, and let stand to separate the liquid; wash the organic phase with anhydrous magnesium sulfate After drying, filter with suction, and concentrate the filtrate under reduced pressure at 50°C until there is no fraction; add 11L of ethanol to the residue, and reflux for beating for 1 hour; after cooling down, filter with suction, and dry the filter cake to obtain compound 4, 471.6g, with a yield of 80.4%. 99.7% purity. [HPLC met...

Embodiment 2

[0034]

[0035] Add 22.0g of compound C and 220mL of dichloromethane into the reaction flask and stir, add 9.5g of triethylamine, and stir at 25±5°C for 10 minutes. Add 16.7g of CDI, continue to stir at 25±5°C for 7 hours, this system is System 1. Add 39.4g of compound 1 and 800mL of dichloromethane into another reaction flask, add 40.5g of methanesulfonic acid dropwise, and stir at 10±5°C for 5 hours. This system is System 2. To System 2, 42.7 g of triethylamine was added dropwise. After the dropwise addition, system 2 was added dropwise into system 1, kept at 25±5°C and stirred for 24 hours. Add 1L of water to the system, stir for 15 minutes to separate the liquids. The organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure at 50°C until no distillate was present, and the residue was added to 1L of ethanol, and stirred under reflux for 1 hour. After cooling down, it was filtered and the filter cake was dried to obtain compound 4, ...

Embodiment 3

[0037]

[0038] Add 22.0 g of compound C and 220 mL of dichloromethane into the reaction flask and stir, then add 9.5 g of triethylamine and stir for 10 minutes. Add 21.5g EDCI and 15.1g HOBT and stir, this system is System 1. Add 39.4g of compound 1 and 800mL of dichloromethane into another reaction flask, add 40.5g of methanesulfonic acid dropwise, and stir at 10±5°C for 5 hours. This system is System 2. To System 2, 42.7 g of triethylamine was added dropwise. After the dropwise addition, system 2 was added dropwise into system 1, and kept stirring for 24 hours. Add 1L of water to the system, stir for 15 minutes to separate the liquids. The organic phase was dried over anhydrous magnesium sulfate, concentrated under reduced pressure at 50°C until no distillate was present, and the residue was added to 1L of ethanol, and stirred under reflux for 1 hour. After cooling down, it was filtered, and the filter cake was dried to obtain compound 4, 28.5 g, with a yield of 61.7%...

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 preparation method of an antithrombotic drug, belongs to the technical field of medicinal chemistry and in particular relates to a preparation method of a direct coagulationfactor Xa inhibitor, which is shown as the following reaction. Compared with the existing process, the preparation method has the advantages of mild reaction condition in each step, high yield, simplicity and convenience operation, stable process and suitability for large-scale industrial production.

Description

technical field [0001] The invention relates to a preparation method of an antithrombotic drug, in particular to a preparation method of a direct blood coagulation factor Xa inhibitor, and belongs to the technical field of medicinal chemistry. Background technique [0002] With the acceleration of the pace of life and the increase of people's life pressure, thrombosis is gradually becoming an important disease that threatens human health. Among high-income groups, thrombosis has become one of the common causes of blood circulation disorders. At the same time It is also relatively common clinically, especially in patients with thrombosis suffering from cardiovascular and cerebrovascular diseases, and its morbidity, disability and mortality are all high. At present, antithrombotic drugs are divided into three categories: antiplatelet aggregation drugs, thrombolytic drugs and anticoagulant drugs. Antiplatelet aggregation drugs mainly play an antithrombotic effect by inhibiting...

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 Patents(China)
IPC IPC(8): C07D513/04C07D213/75A61P7/02
Inventor 凌亚江宁任英梅龚彦春刘永强
Owner JIANGSU VCARE PHARMATECH
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