Compound and preparation method thereof

A technology of compounds and hydrates, applied in the field of compounds and their preparation, can solve the problems of complex reactions, harsh reaction conditions, and low purity, and achieve the effect of simple reaction process, mild reaction conditions, and easy separation and purification

Active Publication Date: 2014-10-01
四川弘远药业有限公司
View PDF7 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The shortcoming of this method is: utilize (-) 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole with higher purity and NaBH4 and BF3 After contacting and reacting in tetrahydrofuran, after a A series of post-treatment processes to obtain relatively pure (S)-(-)2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole, and then react with HCl to obtain (S)-( -)-2-Amino-6-(propylamino)-4,5,6,7-tetrahydrobenzothiazole dihydrochloride, the reaction is complicated, and the reaction conditions are harsh. If necessary, the whole reaction is carried out under the protection of an inert gas. For large-scale production, a large amount of equipment investment will be required to ensure the corresponding harsh reaction conditions
[0011] The disadvantage of this method is that the intermediate N-((S)-2-amino 4,5,6,7-tetrahydrobenzo[D]thiazol-6-yl) propionamide needs to be pure, so as to obtain relatively high yield
The shortcoming of this method is: when borane tetrahydrofuran complex is added dropwise, because borane is volatile, a large amount of bubbles will be produced in the reaction process, a...

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
  • Compound and preparation method thereof
  • Compound and preparation method thereof
  • Compound and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061]Put 40.00g (0.236mol, 1.0 molar equivalent) of the starting material into a 1000ml three-necked reaction flask, add 160.0ml tetrahydrofuran, then add 19.85g (0.236mol, 1.0 molar equivalent) sodium bicarbonate, stir and heat up to 50°C, Add 29.22g (0.225mol, 0.95 mole equivalent) of propionic anhydride dropwise, control the dropwise addition within 1 hour, stir and react for 0.5 hour after the dropwise addition, then cool down to 5±5°C, then add 26.82g (0.708mol, 3.0mol Equivalent) sodium borohydride, dropwise add boron trifluoride ether solution 118.4ml (0.944mol, 4.0 molar equivalent, containing 47.0% boron trifluoride, density 1.15g / ml, Zibo Linzi Xinqiang Chemical Co., Ltd., batch number: 20121008 ), control the dropwise addition in 1 hour, keep stirring for 1 hour after the dropwise addition, naturally rise to room temperature and stir for 1.5 hours, reflux and stir for 1.5 hours; cool down to 10±5°C, add 120.0ml of water dropwise, and add 100.0ml of water after 20 mi...

Embodiment 2

[0064] Put 40.00g (0.236mol, 1.0 molar equivalent) of the starting material into a 2000ml three-necked reaction flask, add 320.0ml of tetrahydrofuran, then add 47.26g (0.472mol, 2.0 molar equivalent) of potassium bicarbonate, stir and heat up to reflux, Start to add 30.76g (0.236mol, 1.0 molar equivalent) of propionic anhydride dropwise, control the dropwise addition within 2 hours, stir and react for 1 hour after the dropwise addition, then cool down to 5±5°C, then add 53.64g (1.416mol, 6.0 Molar equivalent) sodium borohydride, dropwise added boron trifluoride ether solution 207.2ml (1.652mol, 7.0 molar equivalent, containing 47.0% boron trifluoride, density 1.15g / ml, Zibo Linzi Xinqiang Chemical Co., Ltd., batch number: 20121008), control the dropwise addition in 5 hours, keep stirring for 2 hours after the dropwise addition, naturally rise to room temperature and stir for 3 hours, reflux and stir for 3 hours; cool down to 10±5°C, add 120.0ml of water dropwise, and add after ...

Embodiment 3

[0067] Put 40.00g (0.236mol, 1.0 molar equivalent) of the starting material into a 1000ml three-necked reaction flask, add 200ml of tetrahydrofuran, then add 23.82g (0.284mol, 1.2 molar equivalent) of sodium bicarbonate, stir and heat up to reflux, and start Add 30.76g (0.236mol, 1.0 molar equivalent) propionic anhydride dropwise (propionic anhydride is added to 120ml tetrahydrofuran to dilute), control the dropwise addition in 1 hour, stir the reaction for 0.5 hour after the dropwise addition, cool down to 5±5°C, and then add 30.8g (0.813mol, 3.4 molar equivalent) sodium borohydride, dropwise added boron trifluoride ether solution 136.2ml (1.086mol, 4.6 molar equivalent, containing 47.0% boron trifluoride, density 1.15g / ml, Linzixin, Zibo City Strong Chemical Co., Ltd., batch number: 20121008), control the dropwise addition within 3 hours, keep stirring for 1 hour after the dropwise addition, naturally rise to room temperature and stir for 2 hours, reflux and stir for 2 hours;...

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 relates to a compound and a preparation method thereof, and specifically relates to an intermediate for synthesizing pramipexole dihydrochloride and a preparation method thereof. The intermediate is easy to purify. The synthesis of the intermediate comprises the following steps: subjecting (s)-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole to carry out reactions with propionic anhydride, and then reducing the reaction products with a reductant so as to obtain the intermediate. The whole reaction process does not contain any intermediate treatment, and the preparation method has the advantages of simple reaction process, mild reaction conditions, high safety, high yield, and suitability for industrial production.

Description

technical field [0001] The invention belongs to the field of drug synthesis and relates to a compound and a preparation method thereof. Background technique [0002] Parkinson's disease is a common slowly progressive neurodegenerative disease that occurs in middle-aged and elderly people, and is characterized clinically by resting tremor, muscle rigidity, and dyskinesia. With the aging of the population, its prevalence is increasing year by year, and it has become a common neurological disease second only to cerebrovascular disease. For a long time, levodopa-based drug substitution therapy has been the first choice for the treatment of Parkinson's disease, but none of the existing treatments can effectively prevent or even slow down the progression of the disease. Pramipexole hydrochloride can be used alone in the treatment of Parkinson's disease to reduce the incidence of dyskinesia caused by levodopa treatment, and when used in combination with levodopa, it can reduce the...

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 柯潇蔡付波
Owner 四川弘远药业有限公司
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