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

A method for preparing sartan drugs by removing trityl protecting group

A technology of trityl and sartan, which is applied in the field of drug synthesis, can solve the problems of long reaction time, impurity, unsatisfactory yield, and low product purity, and achieve the effects of easy recycling, easy purification, and less by-products

Active Publication Date: 2018-07-06
ZHEJIANG MENOVO PHARMA
View PDF21 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the reaction system needs to be boiled for 8 hours, and the reaction time is too long to avoid the formation of impurities
[0013] Indian chemists have discovered the unusual chemical properties of tritylazoles, which are not as stable under alkaline conditions as everyone imagined, but can be hydrolyzed in dilute solutions such as sodium hydroxide (Chem Pharm Bull 56 ,383(2008)), but this method has no practical application value
In addition, Takeda Pharmaceutical had applied for a patent (US 5578733) in 1996, which added sodium bicarbonate to the methanol / dichloromethane mixture for hydrolysis, but the yield was not satisfactory
[0014] From the analysis of known processes, we can see that the existing methods have certain defects, the purity of the obtained products is not high, and the yield is not ideal.

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 method for preparing sartan drugs by removing trityl protecting group
  • A method for preparing sartan drugs by removing trityl protecting group
  • A method for preparing sartan drugs by removing trityl protecting group

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0032] Example 1 Preparation of Candesartan Cilexetil

[0033] (1) Add 409.2mL of dichloromethane, trityl candesartan cilexetil (42.6g, 0.050mol), 136.4mL of anhydrous methanol and 13.6g of montmorillonite to a 1L reaction flask, and the temperature is raised to 38~42℃ Reflux for 4-24 hours, until the HPLC content of trityl candesartan cilexetil is detected by HPLC <2.0% is the end of the reaction. The reaction solution was filtered, and the filter cake was washed with 68.2 mL of dichloromethane. Combine the filtrate, cool to 20-25°C, add 409.2 mL of water, adjust pH=4.5-5.5 with 1% dilute hydrochloric acid, and stir for 10 min. After standing for 30 min, the separated organic layer was washed twice with 409.2 mL of water.

[0034] (2) The organic layer was evaporated to dryness under reduced pressure. Add methyl tert-butyl ether (MTBE, 341.0 mL) preheated to 35~40℃, add a little seed crystal, cool to 15~25℃, stir for 10h, and filter. The obtained wet product was slurried with ...

Embodiment 2～5

[0037] The operation of Examples 2 to 5 is basically the same as that of Example 1, except that a different solvent is used instead of methylene chloride for the reaction during the reaction; or a different solvent is used instead of methyl tert-butyl ether for beating during post-treatment. The reaction conditions and results are shown in Table 1.

[0038] Table 1 Reaction conditions and test results of Examples 2 to 5

[0039] Example

[0040] a Only use methanol as solvent, reaction time is 25h

Embodiment 6～10

[0042] The operations of Examples 6 to 10 are basically the same as that of Example 1, except that other insoluble acids are used as catalysts instead of montmorillonite for the reaction. The reaction conditions and results are shown in Table 2.

[0043] Table 2 Reaction conditions and test results of Examples 6-10

[0044] Example

catalyst

Yield%

purity%

6

Bentonite

94

99.3

7

Pretreated diatomaceous earth a

94

99.3

8

H-ZSM-1

95

99.2

9

Phosphomolybdic acid

93

99.2

10

no b

86

98.9

[0045] a Before using the diatomaceous earth, stir it with 5% hydrochloric acid for two hours, filter, wash with water until it is neutral, and then dry;

[0046] a The reaction time is 28h.

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 method for preparing sartan drugs by removing a trityl protecting group, which comprises: under the catalysis of an insoluble weak acid, a deprotection reaction occurs between a sartan drug precursor and methanol, and after the reaction is complete, after processing to obtain the sartan drugs. The method has low cost, few by-products, high-quality products, and relatively simple post-treatment. At the same time, montmorillonite can be used as the insoluble weak acid, and the cost is very low, which is convenient for industrial production.

Description

Technical field [0001] The invention belongs to the field of drug synthesis, and relates to a method for removing trityl protecting groups in sartan drugs, and specifically relates to a method for removing trityl protecting groups on tetrazolium in sartan drugs new method. Background technique [0002] Inappropriate activation of the renin-angiotensin-aldosterone system (RAAS) plays a central role in the occurrence and development of some important diseases such as hypertension, heart failure, atherosclerosis, diabetic nephropathy, and people are concerned about this pathogenesis The awareness of is constantly strengthening. Sartan drugs are a kind of high-efficiency and low-toxicity angiotensin II receptor AT1 antagonist (ARB), and its clinical application is more and more extensive. Among the various drugs used to treat hypertension, ARB has become one of the drugs with the fastest increase in the proportion of drugs used. The important reason is the effectiveness and good sa...

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): C07D403/10C07D405/14
CPCY02P20/55
Inventor 亚罗米尔·托曼姚成志陈为人鲍继胜刘雄支浩西廖腾火生
Owner ZHEJIANG MENOVO PHARMA
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