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

Method for preparing asenapine

An intermediate and reaction technology, which is applied in the field of synthesis of organic compounds, can solve the problems of large environmental pollution, lengthy synthesis routes, and the use of flammable and explosive reagents, etc.

Active Publication Date: 2019-12-24
ZHEJIANG AUSUN PHARMA
View PDF9 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0018] In summary, the currently reported synthetic methods of asenapine generally have disadvantages such as cumbersome process operation, great environmental pollution, use of flammable and explosive reagents, and lengthy synthetic routes.

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 asenapine
  • Method for preparing asenapine
  • Method for preparing asenapine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0141]

[0142] Step (b-1): Synthesis of compound VI:

[0143] Add 35.2g of compound V, 63.3g of 48% hydrobromic acid aqueous solution into a 200ml reaction bottle, add 18.4g of sulfuric acid dropwise at room temperature, heat up to 50°C and keep it for 10h, cool to room temperature, add 100ml of dichloromethane, add 50ml of water and 50ml of Wash the organic layer with aqueous sodium carbonate solution, add 10g of sodium sulfate to dry, filter, add 63.1g of triethyl phosphite and 8.6g of anhydrous zinc bromide to the organic layer at one time, heat the reaction solution to 40°C, and stir the reaction mixture After 10 hours, cool slightly, add 100ml of water to wash, separate the water layer, collect the organic phase, and evaporate the solvent to dryness under reduced pressure to obtain compound VI (54.8g, 95.0%).

[0144] Step (b-2): Synthesis of Compound VIII

[0145] Under nitrogen protection, 54.0g of compound VI was dissolved in 500ml of tetrahydrofuran, and 30.1g of...

Embodiment 2

[0167]

[0168] 73.0 g of compound IV was dissolved in 220 g of hypophosphorous acid, cooled to 0-15°C, and 64.0 g of 30% aqueous sodium nitrite solution was added dropwise, and the addition was completed within 2-3 hours. After dropping, control the temperature at 10-20°C and keep stirring for 5-9 hours. Control the temperature below 30°C and add 160g of ammonia water dropwise, adjust the pH of the water layer to 8-9, add 300ml of n-hexane, wash the organic layer with 160ml of water, and evaporate the organic layer to dryness under reduced pressure at 45-50°C to obtain a crude product.

[0169] Add 230ml of n-heptane and 17ml of toluene to the crude product, raise the temperature to 40-50°C and stir to dissolve, then cool and crystallize at a rate of 5-10°C per hour, cool to 20-25°C and stir and crystallize for 1.0-1.5 h, after a large amount of solids are precipitated, cool down to -5~0°C, keep stirring for 1.0h, filter, collect the crystallized asenapine, and dry under v...

Embodiment 3

[0171]

[0172] Step (c-1): Synthesis of Compound Ⅺ

[0173] Add 50.0g of compound V and 75.0g of 48% hydrobromic acid aqueous solution into a 250ml reaction bottle, add 14.0g of sulfuric acid dropwise at room temperature, heat up to 60°C and keep it for 13h, cool to room temperature, add 100ml of toluene, and wash the organic layer with 35.0g of water in turn Wash with 28.0 g of 2.5% aqueous sodium carbonate solution, stand to separate the layers, add 65.2 g of triphenylphosphine to the organic layer, stir at 60° C. for 10 h, then cool to ambient temperature, and filter to obtain compound XI (118.8 g, 95.2%).

[0174] Step (c-2): Synthesis of Compound VIII

[0175]Under nitrogen protection, 102.4g of compound XI was dissolved in 1000ml of tetrahydrofuran, and 37.4g of 5-chlorosalicylaldehyde was added, and 15.8g of pyridine was added dropwise. After the reaction was completed, 600ml of water and 600ml of hexane were added, and saturated with 400ml of sodium carbonate solut...

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
crystallization temperatureaaaaaaaaaa
purityaaaaaaaaaa
Login to View More

Abstract

The invention relates to a method for preparing asenapine. Specifically, the invention relates to a method for preparing a medicinal asenapine free alkali and a crystal form thereof, and also relatesto a preparation method of an intermediate compound used in the method.

Description

technical field [0001] The present invention relates to the field of synthesis of organic compounds. In particular, the present invention relates to the antipsychotic drug Asenapine, the compound trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2 ,3:6,7]-Oxazolo[4,5-c]pyrrole preparation method and its new crystal form. Background technique [0002] Asenapine, the compound trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]-oxa Zolo[4,5-c]pyrrole, its maleate salt is indicated for the emergency treatment of adults with schizophrenia, mania, or mixed episodes with bipolar I disorder. The mechanism of action of asenapine may be related to the antagonism of dopamine D2 and 5-hydroxytryptamine 2A. It is suitable for the treatment of manic or mixed episodes of schizophrenia and bipolar I disorder, and has a good antipsychotic effect. Antipsychotics are now the fifth largest therapeutic class after cholesterol-lowering drugs, with sales of $16.2 billion wo...

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 Applications(China)
IPC IPC(8): C07D491/044C07D207/08
CPCC07D491/044C07B2200/07C07B2200/13C07D207/08A61K31/407A61P25/18
Inventor 郑志国
Owner ZHEJIANG AUSUN PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com