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

The preparation method of cefcapene hydrochloride

A technology of cefcapene pivoxil hydrochloride and hydrochloric acid, which is applied in the field of medicine and chemical industry, and can solve the problems of complicated operation, high cost and low yield

Inactive Publication Date: 2018-04-03
马晓维 +1
View PDF6 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method is complicated to operate, and the cost is high, so it is not suitable for large-scale production
[0006] CN102775425A discloses a one-pot preparation method for the key intermediate of cefcapene axetil, cefcapene diisopropylamine salt. Although the operation is simple, the yield of the method is not high, and the two-step reaction product is only available when the purity is unknown. 67%

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
  • The preparation method of cefcapene hydrochloride
  • The preparation method of cefcapene hydrochloride
  • The preparation method of cefcapene hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] The preparation method of cefcapene pivoxil hydrochloride comprises the steps:

[0035] 1) 29.8 g (100 mmol) of the compound represented by formula I ((Z)-2-(2-tert-butoxycarbonylaminothiazol-4-yl)-2-pentenoic acid)) was stirred and dissolved in 90 mL of pyridine, Add 16 g (140 mmol) of methanesulfonyl chloride at -10°C, stir and react for 2 hours, then filter to obtain a liquid containing the compound represented by formula (II), store it at -15°C, and set aside;

[0036]2) First mix 4.6g of proline, 12.1g (120mmol) of diisopropylamine (120mmol) and 23.1g (85mmol) of 7-ACA in 100ml of methanol and lower the temperature to 10°C, then mix the product obtained in step 1) containing the formula II The liquid of the compound was dripped into the reaction for 2h, naturally rose to room temperature, adjusted the pH of the solution to 4 with 2mol / L hydrochloric acid, extracted, combined the organic phases, concentrated under reduced pressure, recrystallized from methanol, and ...

Embodiment 2

[0042] The preparation method of cefcapene pivoxil hydrochloride comprises the steps:

[0043] 1) 29.8 g (100 mmol) of the compound ((Z)-2-(2-tert-butoxycarbonylaminothiazol-4-yl)-2-pentenoic acid) represented by formula I was dissolved in 80 ml of pyridine with stirring, Add methanesulfonyl chloride at -15°C, stir and react for 1-2 hours, then filter to obtain a liquid containing the compound represented by formula (II), store it at -10°C, and set aside;

[0044] 2) First mix 4.4g of proline, 10.1g (100mmol) of diisopropylamine and 24.5g (90mmol) of 7-ACA in 100m methanol and lower the temperature to 15°C, then mix the product obtained in step 1) containing the formula II The liquid of the compound was dropped into the reaction for 1 hour, and naturally rose to room temperature, and the pH of the solution was adjusted to 4 with 2mol / L hydrochloric acid, extracted with dichloromethane, the organic phases were combined, concentrated under reduced pressure, recrystallized from m...

Embodiment 3

[0050] The preparation method of cefcapene pivoxil hydrochloride comprises the steps:

[0051] 1) 29.8 g (100 mmol) of the compound represented by formula I ((Z)-2-(2-tert-butoxycarbonylaminothiazol-4-yl)-2-pentenoic acid)) was stirred and dissolved in 120 ml of pyridine, Add 14.9 g (130 mmol) of methanesulfonyl chloride at 0°C, stir and react for 2 hours, then filter to obtain a liquid containing the compound represented by formula (II), store it at -15-0°C, and set aside;

[0052] 2) First mix 3.3g of proline, 11.1g (110mmol) of diisopropylamine (110mmol) and 21.8g (80mmol) of 7-ACA in 100m methanol and lower the temperature to 12°C, then mix the product containing formula II obtained in step 1) The liquid of the compound was dropped into the reaction for 2 hours, and naturally rose to room temperature, and the pH of the solution was adjusted to 4 with 2mol / L hydrochloric acid, extracted with dichloromethane, the organic phases were combined, concentrated under reduced press...

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 cefcapene pivoxil hydrochloride. The preparation method comprises the following steps: 1), a compound shown in the formula I is stirred and dissolved in pyridine, methanesulfonyl chloride is added and stirred for reaction, filtering is performed, and a liquid containing a compound shown in the formula II is obtained; 2), 7-ACA reacts with the liquid containing the compound shown in the formula II in the presence of proline and diisopropylamine, and a compound shown in the formula III is obtained; 3), the compound shown in the formula III reacts with potassium carbonate, and a compound shown in the formula IV is obtained; 4), the compound shown in the formula IV reacts with chlorosulfonyl isocyanate in the presence of diisopropylamine, and a compound shown in the formula V is obtained; 5), the compound shown in the formula V and obtained in the step 4) reacts with iodomethyl pivalate in DMF (dimethyl formamide) in the presence of potassium phosphate and copper acetate, a phosphate solution is added to end the reaction, and a compound shown in the formula VI is obtained; 6), cefcapene pivoxil hydrochloride is obtained after deprotection of the compound shown in the formula VI. The method increases product yield greatly and is particularly suitable for mass production, and few by-products are produced.

Description

technical field [0001] The invention belongs to the field of medicine and chemical industry, in particular to a preparation method of cefcapene hydrochloride. Background technique [0002] Cefcapene pivoxil is the third-generation oral cephalosporin antibiotic. It is a new type of cephalosporin antibiotic developed by Shionogi Company in Japan. It has strong antibacterial activity against Gram-positive and Gram-negative bacteria. [0003] Cefcapene pivoxil hydrochloride, chemical name: (6R,7R)-3-((aminocarbonyl)oxy)methyl-7-(((Z)-2-(2-aminothiazol-4-yl)-2 -pentenoyl)amino)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (2,2-dimethyloxypropoxy (methyl) ester hydrochloride monohydrate, there are many reports about its synthetic method at present, but there are various problems. [0004] Ishikura K et al. (The Journal Of Antibiotics.1994, 466-476) disclose a kind of synthetic method of cefcapene pivoxil, which uses 7-aminocephalosporanic acid as a raw material, a...

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): C07D501/34C07D501/04
CPCC07D501/04C07D501/34
Inventor 马晓维孙学华
Owner 马晓维
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