Preparation method of pramipexole hydrochloride

A technology of pramipexole hydrochloride and amino, which is applied in the field of pharmaceutical preparations, can solve the problems of difficult industrial production of pramipexole hydrochloride, low yield, high environmental pollution, etc., achieve broad prospects and industrialization should be valuable, and increase the yield , The effect of cheap and easy-to-obtain raw materials

Active Publication Date: 2019-01-18
ANHUI QINGYUN PHARMA & CHEM
View PDF11 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] This route seems to be a very perfect route. Its materials are cheap and easy to obtain, and the reaction yield is high. However, this route has been repeated many times, and the reports in the literature have not been repeated. It may be related to the stability of the substrate.
[0016] Known by above-mentioned total number, at present about the synthetic route of pramipexole hydrochloride or because of using the big metal oxidizing agent of environmental poll

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 pramipexole hydrochloride
  • Preparation method of pramipexole hydrochloride
  • Preparation method of pramipexole hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0035] The preparation method of a kind of pramipexole hydrochloride proposed by the present invention comprises the following steps: first, p-aminocyclohexanol is condensed and protected with propionyl chloride to obtain p-propionyl cyclohexanol, and then obtained p-propionyl cyclohexanone through catalytic oxidation , followed by oxidative bromination and Hantzsch condensation to obtain 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole, and then reduced by diisobutylaluminum hydride to obtain 2-amino-6- Propylamino-4,5,6,7-tetrahydrobenzothiazole, and then use L-(+)-tartaric acid as a resolving agent to carry out a resolution reaction, and finally form a salt to obtain pramipexole hydrochloride.

Embodiment 2

[0037] The preparation method of a kind of pramipexole hydrochloride proposed by the present invention comprises the following steps: firstly protect the amino group of p-aminocyclohexanol through propionyl chloride condensation to obtain p-propionyl cyclohexanol, wherein, the mixture of propionyl chloride and p-aminocyclohexanol The molar ratio between them is 1:1, and the reaction temperature is -30°C; then, p-propionylcyclohexanone is obtained through catalytic oxidation, wherein, in the catalytic oxidation process, TCCA is selected as the oxidant, TEMPO and NaBr are selected as the catalyst, and dichloro Methane is the solvent, and the molar ratio between propionyl cyclohexanol, TCCA, TEMPO, and NaBr is 2:1:0.02:0.2, and the reaction temperature is -10°C; then it is obtained by one-pot method of oxidative bromination and Hantzsch condensation 2-Amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole, wherein, in the oxidative bromination process, the oxidative bromination re...

Embodiment 3

[0039] The preparation method of a kind of pramipexole hydrochloride proposed by the present invention comprises the following steps: firstly protect the amino group of p-aminocyclohexanol through propionyl chloride condensation to obtain p-propionyl cyclohexanol, wherein, the mixture of propionyl chloride and p-aminocyclohexanol The molar ratio between them is 1.5:1, and the reaction temperature is 30°C; then, p-propionylcyclohexanone is obtained through catalytic oxidation, wherein, in the catalytic oxidation process, TCCA is selected as the oxidant, TEMPO and NaBr are selected as the catalyst, and dichloromethane as a solvent, and the molar ratio between propionyl cyclohexanol, TCCA, TEMPO, and NaBr is 1:0.5:0.01:0.1, and the reaction temperature is 40°C; then 2- Amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole, wherein, in the oxidative bromination process, the oxidative bromination reagent is H 2 o 2 / HBr; and then reduced by diisobutyl aluminum hydride to obtain 2...

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 preparation method of pramipexole hydrochloride. The method comprises the following steps: protecting an amino group of aminocyclohexanol by means of condensation of propionyl chloride to obtain p-propionyl cyclohexanol; then, carrying out catalytic oxidation to obtain p-propionyl cyclohexanone; carrying out oxidative bromination and Hantzsch condensation to obtain 2-amino-6-propionylamino-4, 5, 6, 7-tetrahydrobenzothiazole; then, reducing by using diisobutylaluminum hydride to obtain 2-amino-6-propylamino-4, 5, 6, 7-tetrahydrobenzothiazole; finally, carrying out L-(+)-tartaric acid separation and salification to obtain the pramipexole hydrochloride. The preparation method, provided by the invention, of pramipexole hydrochloride is low in price of raw materials, easy in obtaining of the raw materials, convenient and simple to operate, novel in route, environmentally-friendly and high in yield; the prepared pramipexole hydrochloride is good in purity.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparations, in particular to a preparation method of pramipexole hydrochloride. Background technique [0002] Pramipexole hydrochloride is a new generation non-ergot alkaloid dopamine D2 receptor agonist, chemical name (S)-2-amino-4,5,6,7-tetrahydro-6-propylaminobenzothiazole dihydrochloride Salt-hydrate, which was approved by the US FDA in 1997, is currently the first-line drug for the treatment of Parkinson's disease. In 2007, it was launched in my country under the trade name "Senfulo". Global sales exceeded 1 billion US dollars that year, and the patent period has expired, and major domestic pharmaceutical companies are competing to imitate it. Therefore, the green, environmentally friendly, simple, practical, cheap and easy-to-control process has broad market prospects. [0003] The synthetic technique about pramipexole hydrochloride mainly includes following several at present. [...

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): C07D277/60
CPCC07D277/60
Inventor 黄欢黄庆国李凯施亚琴
Owner ANHUI QINGYUN PHARMA & CHEM
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