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

Method for preparing dexmedetomidine

A technology for medetomidine and imidazole, which is applied in the field of preparation of dexmedetomidine hydrochloride and its intermediates, can solve the problems of reduced yield of main product and unscheduled reaction route, and achieve convenient operation and short synthetic route , to ensure high-quality results

Active Publication Date: 2016-11-09
JIANGSU HENGRUI MEDICINE CO LTD
View PDF6 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the disadvantages of the nucleophilic addition reaction of traditional Grignard reagents to ketones are: in the process of nucleophilic addition reaction, it is usually accompanied by the generation of aldol condensation by-products and reduction by-products of the substrate itself, resulting in the main product The yield is greatly reduced; at the same time, due to the steric hindrance of the reaction substrate or the charge effect of the functional group, the designed reaction route often cannot be carried out as expected.

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
  • Method for preparing dexmedetomidine
  • Method for preparing dexmedetomidine
  • Method for preparing dexmedetomidine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0046] Example 1: Preparation of 1-(2,3-dimethylphenyl)-1-(1-trityl-1H-imidazol-4-yl)ethanol

[0047]

[0048] Step 1: Preparation of 1-trityl-1-H imidazole Grignard reagent

[0049] Under the protection of nitrogen, in a 1L reaction flask, add 4-iodo-1-trityl-1-H imidazole (144g, 330mmol) dissolved in 720ml of tetrahydrofuran, drop ethylmagnesium bromide (330mmol, 1M tetrahydrofuran solution), stirred at room temperature for 30 min, and set aside.

[0050] Step 2: preparation of formula I compound

[0051] Nitrogen protection, add anhydrous ZnCl in Schlenk reactor 2 (4.1g, 30mmol), LiCl (14g, 330mmol), tetrabutylammonium bromide (1M ether solution, 60mL, 60mmol), stirred at room temperature for 15 minutes. Add the tetrahydrofuran solution of (1-trityl-1H-imidazol-4-yl)magnesium bromide prepared above, stir at room temperature for 30 min, concentrate part of the solvent under reduced pressure to about 330 ml, and cool the mixture to 0 °C. Add a solution of 2,3-dimethyla...

Embodiment 13

[0068] Embodiment 13: the preparation of medetomidine

[0069]

[0070] In a 3L reaction flask, put 4-[(2,3-dimethylphenyl)-1-hydroxyethyl]-1-(triphenylmethyl)imidazole 46g (100mmol), triethylsilane 59.3 g, 1400ml of dichloromethane, cooled to -10°C, 80ml of trifluoroacetic acid was added dropwise under stirring, the dropwise was completed in about 1 hour, and the reaction was continued for 4 hours, then slowly raised to room temperature, and reacted overnight. Wash three times with 300ml of saturated sodium bicarbonate solution, once with 300ml of water, dry over anhydrous sodium sulfate, concentrate to dryness, add 650ml of ethyl acetate, extract with 2N hydrochloric acid (75ml×4), combine the extracts, add 10% Pd / C 0.7 g, normal pressure through H 2 Reduce overnight, filter with celite, neutralize with 20% sodium hydroxide solution, extract with ethyl acetate (300ml×2), combine the organic layers, wash with brine (150ml), dry over anhydrous sodium sulfate, and concentr...

Embodiment 14

[0072] Example 14: Preparation of (S)-dexmedetomidine-L-(+)-tartrate

[0073] L-(+)-tartaric acid (9 g, 60 mmol) was added to a solution of medetomidine (12 g, 60 mmol) in ethanol (250 ml). The suspension was heated to reflux until completely dissolved, then stirred overnight at room temperature, and filtered to obtain a white solid (9 g). The resulting solid was dissolved in isopropanol (200ml) under reflux, stirred overnight at room temperature, and filtered to obtain (13.5g). The obtained solid was refined again by the same method to obtain 8.1 g of solid with a purity of 99.9% and a yield of 77.1%.

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 method for preparing dexmedetomidine, and particularly provides a method for preparing medetomidine midbody 1-(2,3-dimethyl phenyl)-1-(1-trityl-1H-imidazole-4-base) ethyl alcohol. The compound medetomidine midbody as shown in formula I is synthesized through Grignard reaction. The invention further provides a method for preparing dexmedetomidine hydrochloride. The technology has the advantages that the number of steps is small, yield is high, operation is easy, and product purity is high and is quite suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of dexmedetomidine hydrochloride and an intermediate thereof. Background technique [0002] Dexmedetomidine Hydrochloride Injection is an α2-adrenoceptor agonist jointly developed by Orion Pharma (Finland) and Abott (USA). Listed in Japan. This product is the dextroisomer of the α2-adrenoceptor agonist medetomidine. Compared with medetomidine, this product is more selective for central α2-adrenoceptor agonism and has a shorter half-life , the dosage is very small, it is clinically suitable for the sedation of intubation and ventilator patients during intensive care treatment, and the marketed dosage form of this product is 2mL injection. [0003] Medetomidine, its chemical name is 5-[1-(2,3-dimethylphenyl) ethyl]-1H-imidazole, and dexmedetomidine is its dextroisomer, which is derived from medetomidine Split to get, the structure is as follows: [0004] [0005] US4544664 discloses the preparation of ...

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): C07D233/64C07D233/58
CPCC07D233/58C07D233/64
Inventor 侯宪山王俊琰王治安仲新光
Owner JIANGSU HENGRUI MEDICINE 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