Check patentability & draft patents in minutes with Patsnap Eureka AI!

Method for preparing granisetron hydrochloride from high tropine alkanamine

A technology for granisetron hydrochloride and tropane amine salt, which is applied in the field of preparing granisetron hydrochloride from high tropane amine salt, can solve the problems of inconvenient storage and transportation, influence, yellowing due to light, etc. Effects of transport and storage, mild conditions, low price

Active Publication Date: 2011-05-18
SINOPHARM CHUANKANG PHARMACEUTICAL CO LTD
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

During the experiment, it was found that the chemical properties of high-tropane amine are active, and it is easy to turn yellow due to light after long-term storage, and it is easy to react with carbon dioxide and water in the air to form carbonate, which affects the progress of the next reaction, and high-tropane Amines are liquid, therefore, not easy to store and transport

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
  • Method for preparing granisetron hydrochloride from high tropine alkanamine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Add 3000ml of dichloromethane, 71.1g of 1-methylindazole-3-carboxylic acid, and 34.6ml of oxalyl chloride into a 5000ml three-necked flask, and stir. 7.1ml of N,N-dimethylformamide was added dropwise, and the reaction was stirred for 4 hours. Evaporate dichloromethane, re-add 3000ml dichloromethane to dissolve, add 130g homotropaneamine hydrochloride, 180ml triethylamine, and stir until the next day. The solution is yellow and transparent. Stirring was stopped and washed three times with saturated sodium bicarbonate solution. Add anhydrous potassium carbonate, stir and dry. Filter and recover dichloromethane under normal pressure, evaporate the solvent under reduced pressure, add 1000ml of absolute ethanol, and adjust the pH value to 2-3 with ethanol solution of hydrogen chloride. Add seed crystals. Filter to get crude product. Recrystallization from water and ethanol gave 110.7 g of the final product. Yield: 87.7%. Melting point: 290.2-291.1°C.

[0032] This ex...

Embodiment 2

[0034] Add 6000ml of chloroform, 142.2g of 1-methylindazole-3-carboxylic acid, and 100ml of thionyl chloride into a 10000ml three-necked flask, and stir. 14.2ml of N,N-dimethylformamide was added dropwise, and the reaction was stirred for 4 hours. Evaporate chloroform, add 3000ml chloroform again to dissolve, add 188g high tropine amine sulfate, 130ml dimethylamine, stir until the next day. The solution is yellow and transparent. Stirring was stopped and washed three times with saturated sodium bicarbonate solution. Extract with water and add 130ml12N hydrochloric acid. The measured pH value is 2-3. Water and 20ml hydrochloric acid were added to extract twice. The aqueous phases were combined and washed once with chloroform. Extract with chloroform plus 10N sodium hydroxide solution, the pH value is 10-11. Extract twice with chloroform, and combine the chloroform layers. Wash once with saturated sodium bicarbonate solution. Wash once with saturated saline. Add anhydro...

Embodiment 3

[0036] Add 6000ml of ethyl acetate, 142.2g of 1-methylindazole-3-carboxylic acid, and 50ml of phosphorus oxychloride into a 10000ml three-necked flask, and stir. 14.2ml of N,N-dimethylformamide was added dropwise, and the reaction was stirred for 4 hours. Evaporate ethyl acetate, add 3000ml ethyl acetate again to dissolve, add 260g high tropine amine dihydrogen sulfate, 240ml diethylamine, stir until the next day. The solution is yellow and transparent. Stop stirring, wash once with water, and wash twice with saturated sodium bicarbonate solution. Extract with water and add 130ml12N hydrochloric acid. The measured pH value is 2-3. Water and 20ml hydrochloric acid were added to extract twice. The combined aqueous phases were washed once with ethyl acetate. Extract with ethyl acetate plus 10N sodium hydroxide solution, the pH value is 10-11. It was extracted twice with ethyl acetate, and the ethyl acetate layers were combined. Wash once with saturated sodium bicarbonate s...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to a method for preparing granisetron hydrochloride from endo-9-methyl-9-azabicyclo[3,3,1]nonan-3-amine salt and solves the problems of inconvenient storage and transportation due to the active chemical properties of endo-9-methyl-9-azabicyclo[3,3,1]nonan-3-amine salt and low purity of the prepared granisetron hydrochloride of the prior preparation of granisetron hydrochloride from the raw material of endo-9-methyl-9-azabicyclo[3,3,1]nonan-3-amine salt. The method comprises the following steps: (1), placing a solvent, a chlorinating agent and 1-methylindazolyl-3-carboxylic acid into a container and stirring the mixture; (2), adding a catalyst into the container and stirring the mixture; (3), evaporating the solvent to dryness to obtain solid powder; (4), adding a solvent, an acid-binding agent and the endo-9-methyl-9-azabicyclo[3,3,1]nonan-3-amine salt into the powder, and stirring the mixture till the solution turns yellow and transparent; (5), washing with water and saturated solution of sodium bicarbonate; (6), adding anhydrous potassium carbonate into the solution, stirring the solution, drying the solution, filtering the solution, reclaiming the solvent at normal temperature and drying the solvent to dryness with reduced pressure; (7), adding an ethanol solution of chlorine hydride into residual liquid and adjusting the pH value of the mixed solutionto 2 to 3; (8), crystallizing the solution and obtaining a coarse product through filtration; and (9), recrystallizing the coarse product and obtaining a fine product of the granisetron hydrochloride.

Description

Technical field: [0001] The present invention relates to the field of organic chemistry. Specifically, the present invention relates to a new method for preparing granisetron hydrochloride from homotropane amine salt. Background technique: [0002] The chemical name of Granisetron is 1-methyl-N-(endo-9-methyl-9-azabicyclo[3.3.1]nonan-3-yl)-1H-indazole-3- amides. Granisetron and its salts are a 5-HT 3 Receptor antagonist, acts directly on 5-HT in the central chemoreceptor area and peripheral vagal nerve endings 3 Receptors, inhibit the occurrence of nausea and vomiting, and have good preventive and therapeutic effects on nausea and vomiting caused by radiotherapy, chemotherapy and surgery. It was developed by Smith-Kline Beecham and launched in South Africa in 1991. Granisetron and other 5-HT 3 Compared with receptor antagonists (such as ondansetron), it has the advantages of higher receptor selectivity, stronger antiemetic effect, less dose, and long-lasting curative e...

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
Patent Type & Authority Patents(China)
IPC IPC(8): A61P1/08C07D451/14
Inventor 艾林刘啸张乐张宏
Owner SINOPHARM CHUANKANG PHARMACEUTICAL CO LTD
Features
  • R&D
  • 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