Synthesis of optically-pure sulfur-containing quaternary heterocyclic drug intermediate

A compound, a sulfolane-based technology, is applied in the synthesis of sulfur-containing four-membered heterocyclic drug intermediates, which can solve the problems of danger, difficulty in operability, low overall synthesis yield, harsh reaction conditions, etc., and achieve optical purity of the product Good, simple equipment and process, high overall yield

Active Publication Date: 2018-08-03
富乐马鸿凯(大连)医药有限公司
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Obviously, in these known methods, the synthesis route is long, resulting in low overall synthesis yield, and the use of azide compounds leads to harsh reaction cond...

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 of optically-pure sulfur-containing quaternary heterocyclic drug intermediate
  • Synthesis of optically-pure sulfur-containing quaternary heterocyclic drug intermediate
  • Synthesis of optically-pure sulfur-containing quaternary heterocyclic drug intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach 1

[0054] Synthesis of Embodiment 1 Compound II

Embodiment 1

[0056] Under stirring, 152 g of DBU was completely dissolved in 400 mL of dichloromethane to prepare an alkaline solution. And the alkali solution was cooled to 0°C in an ice-water bath for use.

[0057] 23.4 g of (±)-BOC-A-phosphonoglycine trimethyl ester was dissolved in 100 mL of dichloromethane, and then the above alkali solution was added dropwise at 0° C. to form a phosphorus ylide solution.

[0058] Next, 5.4 g of thietanone was dissolved in 100 mL of dichloromethane, and then, this solution was added dropwise to the above-mentioned phosphorus ylide solution. At this time, the reaction solution changed from yellow to brown, and then the reaction mixture was warmed to room temperature and reacted overnight. The progress of the reaction was monitored by TLC. After the reaction was completed, dilute hydrochloric acid was added to quench the reaction. The organic phase was obtained after standing for separation. Subsequently, the organic phase was successively washed wi...

Embodiment 2

[0060] Example 2 was carried out in the same manner as in Example 1 above, except that the base used was triethylamine. The product was confirmed by nuclear magnetic resonance spectrum, and the yield was 23%.

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 provides a novel method for synthesizing an optically-pure sulfur-containing quaternary heterocyclic drug intermediate which is (S)-2-[(tert-butyloxycarboryl)-amino]-2-[3-(3-methoxy)-1-cyclopropylsulfonyl]-acetic acid. The method comprises the following steps: taking thietanone as a starting raw material, carrying out Wittig-horner reaction, methoxylation, oxidization and enzymatic catalysis hydrolytic resolution to prepare an optically-pure target compound. The method is easily available in raw materials, simple in requirements on equipment and efficient in synthesis of chiral compounds; the steps can be enlarged to kilogram scale for production; the method is a novel method suitable for industrial application.

Description

technical field [0001] The invention relates to the field of organic synthesis, in particular to a synthesis method of a sulfur-containing four-membered heterocyclic drug intermediate of a deacetylase inhibitor. Background technique [0002] In recent years, enzyme-inhibitor antimicrobials have attracted extensive attention due to their broad-spectrum and high-efficiency. Among them, the deacetylase (LpxC) enzyme inhibitor (as shown in the following formula) has been confirmed as a broad-spectrum antibacterial agent (Curr.Med.Chem.2012,19,2038-2050; mBio.2014,5, 01551-14; Bioorg. Med. Chem. 201119, 852-860). Through in-depth research on such inhibitors, it is expected to design an ideal drug against endotoxin infection with obvious curative effect, low side effects and low price. [0003] [0004] LpxC enzyme inhibitor [0005] In the study on the synthesis of LpxC enzyme inhibitors, it was found that one of the potentially important synthetic units is a chiral drug in...

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): C07D331/04C12P17/00
CPCC07B2200/07C07D331/04C12P17/00
Inventor 于洋赫巍赵新俊高汉荣冯言枢
Owner 富乐马鸿凯(大连)医药有限公司
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