Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Preparation method of indole derivative

A technology for indole derivatives and compounds is applied in the field of preparation of indole derivatives, and can solve the problems of toxic and side effects, affecting the purity of silodosin, and being difficult to purify.

Active Publication Date: 2020-05-08
北京鑫开元医药科技有限公司
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

When preparing silodosin, the content of dehydrogenation impurities is relatively large, and this impurity 5-[(2R)-2-aminopropyl]-1-[3-(benzoyloxy)propyl]-7 -Cyano-1H-indole salt and silodosin are very similar in structure, and the product is an oily substance with low purity, which is difficult to purify in the finished product, and the presence of impurities will not only affect the purity of silodosin, May also cause toxic side effects

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 indole derivative
  • Preparation method of indole derivative
  • Preparation method of indole derivative

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0044] The preparation method of a kind of indole derivative of the embodiment of the present invention comprises the following steps:

[0045] Step S10: Add compound I and base into the first reaction solvent, stir to dissolve, and then add amino protecting agent for reaction. After the reaction is completed, dry and concentrate in the organic phase to obtain compound II, which is 5-[( 2R)-2-aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro-7-cyano-1H-indole tartrate;

[0046] Step S20: adding the compound II into the second reaction solvent, stirring to dissolve, adding an oxidizing agent to react to obtain compound III;

[0047] Step S30: adding the compound III to the third reaction solvent, and using a deprotecting reagent to deprotect the amino group to obtain compound IV;

[0048] Step S40: adding the compound IV and acid into the fourth reaction solvent for reaction to obtain the target compound, which is 5-[(2R)-2-aminopropyl]-1-[3-(benzene Formyloxy)propyl]-7-cyano...

Embodiment 1

[0069] Step S101: In a 500mL three-neck flask, add 5.11g of 5-[(2R)-2-aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro -7-cyano-1H-indole tartrate, 150mL dichloromethane, 5mL triethylamine, and stir;

[0070] After stirring and dissolving, 2.52 g of di-tert-butyl dicarbonate was added in batches, and the reaction was stirred at room temperature for 2 hours to obtain a reaction solution;

[0071] Add 100mL of purified water to the above reaction solution, stir for 10min, and then let stand to separate layers;

[0072] Wash the organic phase after standing and stratifying with 100 mL of purified water and 100 mL of saturated sodium chloride respectively, then dry the organic phase with anhydrous sodium sulfate for 2 h, and then filter to obtain the filtrate;

[0073] The filtrate was concentrated under reduced pressure to obtain 3.84g light yellow oil compound II, and compound II was 5-[(2R)-2-(tert-butoxycarbonyl)aminopropyl]-1-[3-(benzoyloxy )propyl]-2,3-dihydro-7-cyano-1H-...

Embodiment 2

[0092]Step S201: Add 5.15g of 5-[(2R)-2-aminopropyl]-1-[3-(benzoyloxy)propyl]-2,3-dihydro to a 500mL three-necked flask -7-cyano-1H-indole tartrate, 150mL dichloromethane, 5mL triethylamine, and stir;

[0093] After stirring and dissolving, 2.48 g of di-tert-butyl dicarbonate was added in batches, and the reaction was stirred at room temperature for 2 hours to obtain a reaction solution;

[0094] Add 100mL of purified water to the above reaction solution, stir for 10min, and then let stand to separate layers;

[0095] Wash the organic phase after standing and stratifying with 100 mL of purified water and 100 mL of saturated sodium chloride respectively, then dry the organic phase with anhydrous sodium sulfate for 2 h, and then filter to obtain the filtrate;

[0096] The filtrate was concentrated under reduced pressure to obtain 3.86g light yellow oily compound II, and compound II was 5-[(2R)-2-(tert-butoxycarbonyl)aminopropyl]-1-[3-(benzoyloxy )propyl]-2,3-dihydro-7-cyano-1H...

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

PropertyMeasurementUnit
crystallization temperatureaaaaaaaaaa
Login to View More

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a preparation method of an indole derivative. The preparation method comprises the following steps: adding a compound I and an alkali into a first reaction solvent, and adding an amino protective agent for an amino protection reaction, thereby obtaining a compound II; adding the compound II into a second reaction solvent, and then adding an oxidizing agent for an oxidative dehydrogenation reaction to obtain a compound III; adding the compound III into a third reaction solvent, and carrying out an amino deprotection reaction by using a deprotection reagent to obtain a compound IV; and adding the compound IV and an acid into a fourth reaction solvent, and carrying out a salt forming reaction to obtain thetarget compound. The calibration content of such a silodosin intermediate dehydrogenation impurity synthesized by using the preparation method is greater than 95.0%, and the silodosin intermediate dehydrogenation impurity can be used as an impurity standard substance, is applied to qualitative and quantitative research of impurities of a silodosin raw material and preparations thereof, and has important significance for effectively controlling the quality of the silodosin raw material and the preparations thereof.

Description

technical field [0001] The invention belongs to the technical field of medicines, in particular to a preparation method of indole derivatives. Background technique [0002] Silodosin intermediate impurity 5-[(2R)-2-aminopropyl]-1-[3-(benzoyloxy)propyl]-7-cyano-1H-indole salt is indole A type of derivative. The chemical name of silodosin is 1-(3-hydroxypropyl)-5-[(2R)-2-({2-(2,2,2-trifluoroethoxy)phenoxy]ethyl} Amino)propyl]-2,3-dihydro-1H-indole-7-carboxamide is a new generation of α1-adrenoreceptor blockade jointly developed and marketed by Japan’s original Kensei and Japan’s Daiichi Sanko Pharmaceutical Co., Ltd. An agent with outstanding selectivity for adrenergic receptors of the α1A-subtype, capable of selectively relaxing urethral smooth muscle. It also reduces the incidence of hypotension and can be used to treat symptoms of dysuria associated with benign prostatic hyperplasia (BPH) or hypertrophy. When preparing silodosin, the content of dehydrogenation impuritie...

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): C07D209/08
CPCC07D209/08
Inventor 柴国举张鼎武艳朋李静葛志敏戴信敏
Owner 北京鑫开元医药科技有限公司
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
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