Preparation method of 5,6-diethyl-2,3-dihydro-1H-indene-2-amine hydrochloride

A technology of amine hydrochloride and diethyl, applied in the field of synthesis of pharmaceutical intermediates, can solve the problems of industrial production limitation, high price and the like, and achieve the effects of easy industrialization and low price

Inactive Publication Date: 2014-01-29
湖北万知化工医药股份有限公司
View PDF2 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

And raw material 2,3-dihydro-1H-indene-2-amine is rare and expensive commodity on the market, to 5,6-diethyl-2,3-dihydro-1H-indene-2-amine salt There are certain restrictions on the industrial production of acid salts

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
  • Preparation method of 5,6-diethyl-2,3-dihydro-1H-indene-2-amine hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] A preparation method of 5,6-diethyl-2,3-dihydro-1H-indene-2-amine hydrochloride, the steps are as follows:

[0023] (1) Synthesis of compound Ⅰ

[0024] Put 780g of aluminum trichloride and 8L of dichloromethane into a 10L three-necked flask, cool to -1-1°C, add 600g of 3-chloropropionyl chloride dropwise, react for 30min after dropping, and then add 500g ethylbenzene dropwise, after the addition is complete Warm up to room temperature (20-25℃) and react for 8 hours, then pour the reactants into 10L 1M hydrochloric acid ice water (hydrochloric acid ice water mixture) to extract, extract with dichloromethane, wash with saturated sodium bicarbonate once, and wash once with water. The product was dried with sodium sulfate, spin-dried, then freeze-crystallized, and dried to obtain 847 g of solid with a melting point of 63-64°C. The product was confirmed by nuclear magnetism and the yield was 90%.

[0025] (2) Synthesis of compound Ⅱ

[0026] Put 1.5L of 98% concentrated sulfuric a...

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 belongs to the technical field of synthesis of a medical immediate, and particularly relates to a synthesis method of a key intermediate 5,6-diethyl-2,3-dihydro-1H-indene-2-amine hydrochloride of indacaterol. The method comprises the following steps: by taking ethylbenzene as a raw material, preparing a compound I by propionyl chloride; preparing a compound II from the compound I by cyclization reaction; preparing a compound III by reaction of the compound II and butyl nitrite; preparing a compound IV from the compound III by palladium hydrogen reduction; finally preparing a compound V from the compound IV under protection of trifluoroacetyl; preparing a compound VI from the compound V by amino acetylation reaction; preparing a compound VII from the compound VI by reduction; carrying out deprotection, hydrolysis and acidification on the compound VII, so as to obtain the final product compound VIII, namely the 5,6-diethyl-2,3-dihydro-1H-indene-2-amine hydrochloride. The method disclosed by the invention is simple and convenient to operate, reasonable in reaction flow, low in cost, good in product quality, free of pollution to environment, and applicable to industrial production; the content is greater than 99%.

Description

Technical field [0001] The invention relates to the technical field of the synthesis of pharmaceutical intermediates, in particular to the synthesis of 5,6-diethyl-2,3-dihydro-1H-indene-2-amine hydrochloride, a key intermediate of indacaterol method. Background technique [0002] Indacaterol is a new type of ultra-long-acting β2 receptor agonist developed by Novartis of Switzerland. The drug was approved by the US FDA on July 1, 2011. This medicine is used to treat patients with chronic bronchial obstructive disease (COPD) airflow obstruction, including chronic bronchitis and / or emphysema. 5,6-Diethyl-2,3-dihydro-1H-inden-2-amine hydrochloride is the most critical intermediate of indacaterol, and its market prospects and economic benefits therefore have great potential. [0003] The synthesis method of 5,6-diethyl-2,3-dihydro-1H-indene-2-amine hydrochloride reported in the literature (such as Organic Process Research & Development 2006, 10, 135141) is mainly based on 2,3- Dihyd...

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 Applications(China)
IPC IPC(8): C07C211/42C07C209/00C07C209/30
Inventor 鲁东安周叶兵杜小兰刘杰
Owner 湖北万知化工医药股份有限公司
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