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

Acetylaniline compounds and application thereof in preparation of mirabegron

A technology of phenylacetamide and compound, applied in the new preparation field of mirabegron, can solve the problems of unstable aldehyde properties, difficult to control, difficult and the like

Active Publication Date: 2014-09-03
NANJING HERON PHARMA SCI & TECH CO LTD
View PDF7 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Since the intermediate needs to be oxidized from alcohol to aldehyde, this step reaction is not easy to control after amplification, and it is easy to be further oxidized to acid, and the property of aldehyde is unstable. Therefore, industrial production is more difficult.

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
  • Acetylaniline compounds and application thereof in preparation of mirabegron
  • Acetylaniline compounds and application thereof in preparation of mirabegron
  • Acetylaniline compounds and application thereof in preparation of mirabegron

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] 1. Preparation of (R)-N-(4-nitrophenethyl)-2-hydroxy-2-phenylacetamide

[0035] Add 141g (0.93mol) of (R)-2-hydroxy-2-phenylacetic acid, 180g (0.95mol) of (4-nitrophenyl)methylamine hydrochloride, and 187g (1.86mol) of triethylamine into the reaction flask , DMF 700ml, then add 125g hydroxybenzotriazole (0.93mol), EDCI 178g (0.93mol), then stir the reaction at room temperature for 5h, add 2L water to the reaction solution, add ethyl acetate to extract 3 times, and combine the organic layers , washed 3 times with water, then the organic layer was concentrated to dryness, the residue was recrystallized with 1L toluene, filtered, and dried in vacuo to obtain yellow crystals (R)-N-(4-nitrophenethyl)-2-hydroxy- 2-phenylacetamide 249g, yield 89%; FAB-MS (m / z): 301.2(M+H)+

[0036] 2. Preparation of (R)-N-(4-aminophenethyl)-2-hydroxy-2-phenylacetamide

[0037] Add (R)-N-(4-nitrophenethyl)-2-hydroxy-2-phenylacetamide 240g (0.8mol) into the reaction flask, add methanol (1.6L),...

Embodiment 2

[0047] 1. Preparation of (R)-N-(4-nitrophenethyl)-2-hydroxy-2-phenylacetamide

[0048] Add (R)-2-hydroxy-2-phenylacetic acid 90g (0.59mol), (4-nitrophenyl)methylamine hydrochloride 114g (0.60mol), triethylamine 119g (1.18mol) into the reaction flask , DMF 700ml, then add 72g 4-dimethylaminopyridine (0.59mol), dicyclohexylcarbodiimide 122g (0.59mol), then stir the reaction at room temperature for 5h, add 1.4L water to the reaction solution, add ethyl acetate Extracted 3 times, combined the organic layers, washed 3 times with water, then concentrated the organic layer to dryness, the residue was recrystallized with 0.64L toluene, filtered, and dried in vacuo to obtain yellow crystals (R)-N-(4-nitrobenzene Ethyl)-2-hydroxy-2-phenylacetamide 137g, yield 77%; FAB-MS (m / z): 301.2(M+H)+

[0049] 2. Preparation of (R)-N-(4-aminophenethyl)-2-hydroxy-2-phenylacetamide

[0050] Add (R)-N-(4-nitrophenethyl)-2-hydroxy-2-phenylacetamide 125g (0.4mol) into the reaction flask, add methanol ...

Embodiment 3

[0060] 1. Preparation of (R)-N-(4-nitrophenethyl)-2-hydroxy-2-phenylacetamide

[0061] Add (R)-2-hydroxy-2-phenylacetic acid 100g (0.66mol), (4-nitrophenyl)methylamine hydrochloride 126g (0.67mol), triethylamine 133g (1.32mol) into the reaction flask , DMF 600ml, then add 90g 1-hydroxy-7-azobenzotriazole (0.66mol), DIC 83g (0.66mol), then stir the reaction at room temperature for 5h, add 1.5L water to the reaction solution, add ethyl acetate The ester was extracted 3 times, the organic layers were combined and washed 3 times with water, then the organic layer was concentrated to dryness, the residue was recrystallized with 0.7L toluene, filtered, and dried in vacuo to obtain yellow crystals (R)-N-(4-nitro Phenylethyl)-2-hydroxy-2-phenylacetamide 156g, yield 79%; FAB-MS (m / z): 301.2(M+H) +

[0062] 2. Preparation of (R)-N-(4-aminophenethyl)-2-hydroxy-2-phenylacetamide

[0063] Add (R)-N-(4-nitrophenethyl)-2-hydroxy-2-phenylacetamide 145g (0.48mol) into the reaction flask, ad...

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 new intermediate (R)-N-(4-amino phenethyl)-2-hydroxy-2-acetylaniline for preparing mirabegron, and a method for preparing the mirabegron through the intermediate. The method is simple and convenient to operate, has low cost, and is applicable to industrial production.

Description

technical field [0001] The present invention relates to a new preparation method of Mirabegron, in particular to a new intermediate (R)-N-(4-aminophenethyl)-2-hydroxyl-2-phenylacetamide or its salt, and its Application in the synthesis of mirabegron. Background technique [0002] Mirabegron is a selective β3-adrenergic receptor agonist, which is mainly used clinically for the treatment of overactive bladder in adults. Its chemistry is: (R)-2-(2-amino-1,3-thiazol-4-yl)-4'-[2-[(2-hydroxy-2-phenylethyl)amino]ethyl]benzene Acetamide has the following structural formula: [0003] [0004] Mirabegron tablet was developed by Japan Astel-las pharmaceutical company, and was listed in Japan on September 16, 2011, and was approved by the FDA on June 28, 2012 for the treatment of adult overactive bladder ( OAB), trade name Myrbetriq. [0005] The synthetic method of mirabegron in the prior art mainly contains following several kinds: [0006] Method 1: The synthesis method of mi...

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): C07C235/34C07C231/12C07D277/40
Inventor 郭彦飞胡永康袁尚黄文娟魏丹孙晓
Owner NANJING HERON PHARMA SCI & TECH CO LTD
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