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

Synthetic method of pramipexole impurity B

A technology of pramipexole and synthesis method is applied in the field of preparation of pramipexole impurities to achieve the effects of simple process route and convenient operation.

Inactive Publication Date: 2017-06-30
HONGGUAN BIO PHARMA CO LTD
View PDF2 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The synthesis method of pramipexole impurity B has not yet been reported in existing patents and literature

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
  • Synthetic method of pramipexole impurity B
  • Synthetic method of pramipexole impurity B
  • Synthetic method of pramipexole impurity B

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Step 1: Synthesis of (S)-N,N'-(4,5,6,7-tetrahydrobenzothiazole-2,6-diyl)dipropionamide

[0023]

[0024] At room temperature, (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole (5.00g, 29.54mmol), triethylamine (8.97g, 88.63 mmol), propionic anhydride (9.61 g, 73.86 mmol) and DMAP (361 mg, 2.95 mmol). After the addition, the temperature of the system was raised to reflux for 2 hours. TLC detects that the reaction of raw materials is complete. Concentrate the reaction system to dryness, add 10 g of water and 40 g of ethyl acetate, stir vigorously for 3 hours, filter, and wash the filter cake with a little water and ethyl acetate. The obtained solid was transferred to an air blower at 60° C. and dried to constant weight to obtain 4.3 g with a yield of 51%.

[0025] Step 2: (S)-N 2 ,N 6 -Synthesis of dipropyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine

[0026]

[0027] Add (S)-N,N'-(4,5,6,7-tetrahydrobenzothiazole-2,6-diyl)dipropionamide (1.00g, 3.55mmol) to tetr...

Embodiment 2

[0029] Step 1: Synthesis of (S)-N,N'-(4,5,6,7-tetrahydrobenzothiazole-2,6-diyl)dipropionamide

[0030]

[0031] Add (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole (5.00g, 29.54mmol), pyridine to 1,4-dioxane (50mL) at room temperature (11.53g, 88.63mmol), propionic anhydride (9.61g, 73.86mmol) and DMAP (361mg, 2.95mmol). After the addition, the temperature of the system was raised to reflux for 2 hours. TLC detects that the reaction of raw materials is complete. Concentrate the reaction system to dryness, add 10 g of water and 40 g of ethyl acetate, stir vigorously for 3 hours, filter, and wash the filter cake with a little water and ethyl acetate. The obtained solid was transferred to an air blower at 60° C. and dried to constant weight to obtain 3.8 g with a yield of 45.7%.

[0032] Step 2: (S)-N 2 ,N 6 -Synthesis of dipropyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine

[0033]

[0034] Add (S)-N,N'-(4,5,6,7-tetrahydrobenzothiazole-2,6-diyl)dipropane to 1,4-dioxa...

Embodiment 3

[0036] Step 1: Synthesis of (S)-N,N'-(4,5,6,7-tetrahydrobenzothiazole-2,6-diyl)dipropionamide

[0037]

[0038] At room temperature, (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole (5.00g, 29.54mmol), N,N-diisopropyl Ethylamine (11.45 g, 88.63 mmol), propionic anhydride (9.61 g, 73.86 mmol) and DMAP (361 mg, 2.95 mmol). After the addition, the temperature of the system was raised to reflux for 2 hours. TLC detects that the reaction of raw materials is complete. Concentrate the reaction system to dryness, add 10 g of water and 35 g of ethyl acetate, stir vigorously for 3 hours, filter, and wash the filter cake with a little water and ethyl acetate. The obtained solid was transferred to an air blower at 60° C. and dried to constant weight to obtain 4.8 g with a yield of 57.7%.

[0039] Step 2: (S)-N 2 ,N 6 -Synthesis of dipropyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine

[0040]

[0041] Add (S)-N,N'-(4,5,6,7-tetrahydrobenzothiazole-2,6-diyl)dipropionamide (1.00g, ...

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 belongs to the technical field of medicine production and in particular to a preparation method of a pramipexole impurity. The synthetic method of the pramipexole impurity B comprises the following steps of: S1, adding (S)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole, alkali, propionic anhydride and DMAP into an organic solvent to synthesize (S)-N,N'-(4,5,6,7-tetrahydrobenzothiazole-2,6-diyl)dipropanamide; and S2, adding the (S)-N,N'-(4,5,6,7-tetrahydrobenzothiazole-2,6-diyl)dipropanamide obtained by the reaction in the S1 into an organic solvent and reducing system, wherein the reaction product is the pramipexole impurity B. The synthetic method of the pramipexole impurity B is simple in process route and convenient to operate, and the synthesized pramipexole impurity B can be used as a reference substance for detecting related substances of pramipexole, and the method is applied to quality control of pramipexole and related preparations.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical production, in particular to a preparation method of pramipexole impurities. Background technique [0002] The chemical name of pramipexole hydrochloride is (S)-2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole dihydrochloride, and the English name is Pramipexole dihydrochloride, which is a new generation of non-ergot Base D2 and D3 dopamine receptor agonists. Pramipexole hydrochloride was developed by Berliner Ingelheim, Germany, and was approved by the FDA in May 1997 to be listed in the United States under the trade name Mirapex. [0003] (S)-N 2 ,N 6 -Dipropyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine is one of the impurities contained in the finished product of pramipexole hydrochloride, called pramipexole impurity B, CAS number It is 1246815-83-7, the structural formula is as follows: [0004] [0005] Pramipexole impurity B is used as a reference substance for the detec...

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
CPCC07D277/60C07B2200/07
Inventor 杨继斌程宜兴朱金龙张超王奇超张熠能
Owner HONGGUAN BIO PHARMA CO LTD
Features
  • Generate Ideas
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com