Preparation method of pramipexole

An amino, tetrahydrogen technology, applied in the field of pramipexole, can solve the problems of unfavorable industrial production, irritating odor, harsh reaction conditions, etc., and achieve the effects of easy control, improved safety, and mild reaction conditions

Inactive Publication Date: 2010-03-24
BEIJING D VENTUREPHARM TECH DEV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] And patent CN1834092 replaces borane (see route 2) with the ether solution of boron trifluoride, but the ether solution of boron trifluoride decomposes with water, has pungent smell, is highly flammable, and the reaction conditions are harsh, and is also unfavorable for suitability for industrialized production

Method used

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  • Preparation method of pramipexole
  • Preparation method of pramipexole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] 10 L of tetrahydrofuran and 1.2 kg of sodium borohydride were successively added into a 20 L three-necked flask, and stirred for 1 hour. At T=25°C, 1 kg of (±) 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole was added, stirred for 4 hours, and heated to reflux for 48 hours. Natural cooling to 20 ℃ ~ 25 ℃. Slowly pour the reaction solution into 8 L of ice water, and add 6.4 kg of 37% hydrochloric acid dropwise at T=10°C to 20°C. After dropping, PH=1. After suction filtration, a colorless transparent liquid was obtained, and tetrahydrofuran was spin-off under reduced pressure to constant weight. After spinning, adjust the pH to 14 with 50% aqueous sodium hydroxide solution, and consume 7 L of aqueous sodium hydroxide solution. Stir for 1 hour. After suction filtration, the solid was air-dried at 50° C. to constant weight to obtain 870 g of off-white solid (±) 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole, with a yield of 93%.

[0018] ( 1 H-NMR (400...

Embodiment 2

[0020] 10 L of tetrahydrofuran and 1.2 kg of sodium borohydride were successively added into a 20 L three-necked flask, and stirred for 1 hour. Add (-) 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole 1kg at T=25°C, stir for 4 hours, and heat to reflux for 48 hours. Natural cooling to 20 ℃ ~ 25 ℃. Slowly pour the reaction solution into 8 L of ice water, and add 6.4 kg of 37% hydrochloric acid dropwise at T=10°C to 20°C. After dropping, PH=1. After suction filtration, a colorless transparent liquid was obtained, and tetrahydrofuran was spin-off under reduced pressure to constant weight. After spinning, adjust the pH to 14 with 50% aqueous sodium hydroxide solution, and consume 7 L of aqueous sodium hydroxide solution. Stir for 1 hour. Suction filtration, and the solid was air-dried at 50° C. to constant weight to obtain 870 g of off-white solid (-) 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole with a yield of 93%.

[0021] ( 1 H-NMR (400MHz, DMSO); δ(ppm):...

Embodiment 3

[0023] 10 L of tetrahydrofuran and 1.2 kg of lithium aluminum hydride were successively added into a 20 L three-necked flask, and stirred for 2 hours. When T=28°C, 1 kg of (±) 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole was added, stirred for 5 hours, and heated to reflux for 48 hours. Natural cooling to 20 ℃ ~ 25 ℃. Slowly pour the reaction solution into 8 L of ice water, and add 6.4 kg of 37% hydrochloric acid dropwise at T=10°C to 20°C. After dropping, PH=1. After suction filtration, a colorless transparent liquid was obtained, and tetrahydrofuran was spin-off under reduced pressure to constant weight. After spinning, adjust the pH to 14 with 50% aqueous sodium hydroxide solution, and consume 7 L of aqueous sodium hydroxide solution. Stir for 1 hour. After suction filtration, the solid was air-dried at 50° C. to constant weight to obtain 870 g of off-white solid (±) 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole, with a yield of 93%.

[0024] ( 1 H...

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Abstract

The invention discloses a preparation process of pramipexole, namely enantiomers or racemates of 2-amino-6-acrylamido-4,5,6,7-tetrahydrobenzothiazole. The pramipexole is prepared from 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole as the raw material by the reduction reaction with a reducing agent. The process has easy operation, and mild reaction condition, is easy to control, and greatly improve the safety of production.

Description

technical field [0001] The invention relates to a preparation process of pramipexole, the optically active or racemic form of 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole. Background technique [0002] Parkinson's disease is a common neurological disease, which is common in the elderly. [0003] Pramipexole is a non-ergot derivative, and its advantages are: pramipexole acts highly selectively on DA-2 receptors; it can be used alone to treat Parkinson's disease in the early stage, and it can be used in combination with dopamine to treat Parkinson's disease in the late stage. At the same time abroad, pramipexole is used to treat RLS disease (restless leg syndrome), and it is considered to be effective, and pramipexole has a protective effect on the nerves of dopamine. Neuroprotection and the treatment of RLS disease are its unique advantages. Greatly delay the development of the disease and ensure the health of patients. [0004] Non-ergot derivatives are currently ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D277/60A61P25/16
Inventor 王世峰谌伦华康彦龙
Owner BEIJING D VENTUREPHARM TECH DEV
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