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A kind of preparation method of pramipexole hydrochloride

A technology of pramipexole hydrochloride and cyclohexanol, which is applied in the field of preparation of pramipexole hydrochloride, can solve the problems of high environmental pollution, difficulty in industrial production of pramipexole hydrochloride, low yield, etc. Prospects and industrialization should be valuable, and the effect of cheap and easy-to-obtain raw materials

Active Publication Date: 2022-05-10
ANHUI QINGYUN PHARMA & CHEM
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  • 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 pollution, or have used the reduction reagent that exists toxicity big and explosive danger, or because route is long, yield is low, or because route Difficulty in achieving repetition and other reasons lead to difficulties in the industrial production of pramipexole hydrochloride, so the development of cheap and easy-to-get raw materials, green environmental protection, high yield, and good purity of pramipexole hydrochloride synthesis process route has broad prospects

Method used

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  • A kind of preparation method of pramipexole hydrochloride
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  • A kind of preparation method of pramipexole hydrochloride

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Embodiment 1

[0035] 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-propionylamino cyclohexanol, and then obtain p-propionylamino cyclohexanol through catalytic oxidation Hexanone, 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: first, p-aminocyclohexanol is condensed with propionyl chloride to protect the amino group to obtain p-propionylaminocyclohexanol, wherein, propionyl chloride and p-aminocyclohexanol The molar ratio between them is 1:1, and the reaction temperature is -30°C; Then, p-propionylaminocyclohexanone 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 is used as a solvent, and the molar ratio between propionylaminocyclohexanol, TCCA, TEMPO, and NaBr is 2:1:0.02:0.2, and the reaction temperature is -10°C; then oxidative bromination and Hantzsch condensation Pot method to obtain 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole, wherein, in the oxidative bromination process, the oxidative bromination reagent is H 2 o ...

Embodiment 3

[0039] The preparation method of a kind of pramipexole hydrochloride proposed by the present invention comprises the following steps: first, p-aminocyclohexanol is condensed with propionyl chloride to protect the amino group to obtain p-propionylaminocyclohexanol, wherein, propionyl chloride and p-aminocyclohexanol The molar ratio between is 1.5:1, and reaction temperature is 30 ℃; Then obtain p-propionylaminocyclohexanone through catalytic oxidation, wherein, in the catalytic oxidation process, select TCCA as oxidant for use, select TEMPO, NaBr as catalyst for use, select two Chloromethane is used as a solvent, and the molar ratio between propionylaminocyclohexanol, TCCA, TEMPO, and NaBr is 1:0.5:0.01:0.1, and the reaction temperature is 40°C; and then oxidative bromination and Hantzsch condensation one-pot method Obtain 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; a...

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Abstract

The invention discloses a preparation method of pramipexole hydrochloride, which comprises the following steps: p-aminocyclohexanol is condensed and protected by propionyl chloride to obtain p-propionyl cyclohexanol, and then catalyzed to obtain p-propionyl cyclohexanone, and then Oxidative bromination and Hantzsch condensation to give 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole, and reduction with diisobutylaluminum hydride to give 2-amino-6-propylamino ‑4, 5, 6, 7‑tetrahydrobenzothiazole, finally separated by L‑(+)‑tartaric acid and salified to obtain pramipexole hydrochloride. The preparation method of pramipexole hydrochloride proposed by the invention has cheap and easy-to-obtain raw materials, convenient and simple operation, novel route, environmental protection, high yield, and the prepared pramipexole hydrochloride has good 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

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D277/60
CPCC07D277/60
Inventor 黄欢黄庆国李凯施亚琴
Owner ANHUI QINGYUN PHARMA & CHEM
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