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

Synthetic method of mirabegron intermediate

A synthetic method and intermediate technology, applied in the field of drug synthesis, can solve the problems of cumbersome post-processing steps, unfriendly environment, difficult recycling, etc., and achieve the effect of facilitating large-scale industrial production, high feasibility of industrial operation, and reducing production costs

Inactive Publication Date: 2016-07-27
UNIV OF JINAN
View PDF5 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The post-processing steps of this route are cumbersome and generate a lot of waste, and the cost is high and there are many by-products
In the second step of amide reduction, expensive borane-tetrahydrofuran solution and 1,3-dimethylimidazolidinone are used, and the recovery is difficult, resulting in high production costs. Borane-tetrahydrofuran has a foul smell and reacts with water It is violent and emits flammable gas, can form explosive peroxides, is irritating to eyes, skin, and respiratory system, and is not friendly to the environment

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
  • Synthetic method of mirabegron intermediate
  • Synthetic method of mirabegron intermediate
  • Synthetic method of mirabegron intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Preparation of intermediate (I): Add R-mandelic acid (12.17g, 80mmol, 1eq), triethylamine (23.28mL, 168mmol, 2.1eq) and dichloromethane (100mL ). Under ice bath, slowly add pivaloyl chloride (19.29g, 160mmol, 2.0eq) dropwise, keep the temperature of the reaction system not exceeding 5°C, after the dropwise addition is completed, rise to room temperature, add water (15mL) and slowly raise the temperature to 60°C for reaction After 3h, the reaction was completed and cooled to room temperature to obtain the mixed anhydride intermediate (I).

[0029] Preparation of intermediate (II): at room temperature, slowly add 4-nitrophenethylamine (12.61g, 76mmol, 0.95eq) dropwise to the dichloromethane / water solution of the above-mentioned mixed anhydride intermediate (I), dropwise After the addition was completed, the reaction was carried out at room temperature for 2h. After the reaction is completed, wash with 1 mol / L dilute hydrochloric acid (20 mL), separate layers, concentrat...

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 synthetic method of a mirabegron intermediate (R)-2-(4-nitrobenzene ethyl amino)-1-phenyl ethanol hydrochloride (M-02) and belongs to the field of drug synthesis. The method comprises steps as follows: (1) R-mandelic acid and pivaloyl chloride produce a mixed anhydride intermediate (I); (2) the mixed anhydride intermediate (I) and 4-nitrobenzene ethylamine are subjected to an acrylation reaction to produce an intermediate (II); (3) a mirabegron intermediate (M-01) is obtained through hydrolysis of the intermediate (II); (4) an amido bond of the intermediate (M-01) is reduced and the mirabegron intermediate (M-02) is obtained. The reaction condition is mild, the yield is high, few impurities exist, the production cost is low, and the method is suitable for mass industrial production.

Description

technical field [0001] The invention belongs to the field of medicine synthesis and relates to a synthesis method of mirabegron intermediate (R)-2-(4-nitrophenethylamino)-1-phenylethanol hydrochloride. Background technique [0002] In recent years, Overactive Bladder (OAB) has become a major disease that plagues people and seriously affects the quality of life of patients. Increased nocturia. In June 2012, the US FDA approved mirabegron (mirabegron, trade name Myrbetriq) for the treatment of overactive bladder in adults, with the following structural formula: [0003] . [0004] European patents (EP1440969, EP1559427) involve a synthesis of mirabegron and its intermediate (R)-2-(4-nitrophenethylamino)-1-phenylethanol hydrochloride (M-02) Synthetic method, described method synthetic route is as follows: [0005] [0006] [0007] . [0008] In the first step of this route, the condensation of Mirabegron intermediate (R)-2-hydroxyl-N-(4-nitrophenethyl)-2-phenyla...

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): C07C215/30C07C213/02C07C213/08
CPCC07C213/02C07C213/08C07C231/02C07C231/12C07C215/30C07C235/34
Inventor 战付旭张启龙郑庚修
Owner UNIV OF JINAN
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