Preparation method of asenapine and intermediate used for preparing asenapine

A general formula and compound technology, applied in the production of bulk chemicals, organic chemistry, etc., can solve problems such as low yield, complicated post-processing, and difficult to obtain reactants

Inactive Publication Date: 2015-10-14
YANGPU HG PHARMA
View PDF2 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, there are still many problems in the method disclosed in the prior art, such as low yield, difficult to obtain reactants, harsh reaction con

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
  • Preparation method of asenapine and intermediate used for preparing asenapine
  • Preparation method of asenapine and intermediate used for preparing asenapine
  • Preparation method of asenapine and intermediate used for preparing asenapine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0208] In order to make the present invention easier to understand, the present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. Moreover, the specific experimental methods not mentioned in the following examples are all carried out according to conventional experimental methods.

[0209] The raw materials and reagents used in the following examples were purchased from Shanghai Kaisai Chemical Co., Ltd.

Embodiment 1A

[0213] Synthesis of compounds represented by general formula (3A)

[0214] At room temperature, add absolute ethanol (300ml) into a 500ml eggplant-shaped bottle, stir, and add metallic sodium (1.9g, 84mmol) under nitrogen protection, and obtain sodium ethoxide after the sodium is completely dissolved.

[0215] Then, the compound represented by the general formula (1A) (52 g, 280 mmol) and the compound represented by the general formula (2A) (53.6 g, 364 mmol) were sequentially added. React at room temperature for 5-7 hours until the reaction is complete. After suction filtration, the filter cake was washed with methanol (100ml) and dried to obtain a pale yellow solid (49.3g, yield: 56%).

[0216] 1 H NMR (400Hz, CDCl 3 ): δ8.54(s,1H);7.98(s,1H);7.83-7.88(d,1H);7.57-7.61(d,1H);7.04-7.10(m,2H);7.16-7.25(t ,1H); 7.38-7.44(d,1H); 3.92(s,3H).

[0217] MS: 315 (M+1).

Embodiment 2A

[0219] Synthesis of compounds represented by general formula (4A)

[0220] Acetonitrile (250ml) was added to a 500ml eggplant flask. Add the compound (45g, 143mmol), tetrabutylammonium fluoride (11.2g, 42.9mmol) and trimethylsilyl cyanide (26.8ml, 214.5mmol) represented by the general formula (3A) successively under stirring at room temperature, and heat up to 40°C, react for 30-40 minutes until the reaction is complete. After cooling, the reaction solution was poured into a beaker filled with water (200ml), and stirred while pouring to precipitate solids. After stirring for 30 minutes, the filter cake was stirred and washed with methanol (30 ml), filtered with suction, and dried to obtain a white solid (30.8 g, yield: 63%).

[0221] 1 H NMR (400Hz, DMSO-d 6 ):δ:8.08(s,1H);7.82-7.89(d,1H);7.63-7.68(d,1H);7.17-7.22(d,1H);6.91-6.98(m,3H);4.38(s ,1H); 4.32(s,1H); 3.74(s,3H).

[0222] MS: 342 (M+1).

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 method for preparing asenapine shown in a general formula (11) and an intermediate shown in a general formula (8) and used for preparing asenapine. The general formulas are shown in the specification. The method comprises the following steps: obtaining a compound shown in a general formula (9) through ring-closure reaction of the compound shown in the general formula (8); obtaining a compound shown in a general formula (10) through reduction reaction of the compound shown in the general formula (9); obtaining asenapine shown in the general formula (11) through substitution reaction of the compound shown in the general formula (10), wherein in the general formula (8), R1 represents halogen, preferably chlorine or bromine.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a method for preparing asenapine and an intermediate for preparing asenapine. Background technique [0002] Asenapine means trans-5-chloro-2-methyl-233a12b-tetrahydro-1H-dibenzo[23:67]-oxa And[4,5-c]pyrrole (Trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenz[2,3:6,7]oxepino[4,5-c] pyrrole), a compound with central nervous system depressant activity and antihistamine and antiserotonin activity. Asenapine is a racemate comprising the following two optical isomers: [0003] [0004] For convenience, racemates covering both enantiomers are represented herein as single isomer structural formulas. It has been confirmed that the maleate salt of asenapine is a broad-spectrum, high-potency serotonin, norepinephrine and dopamine antagonist widely used in the treatment of patients with schizophrenia. [0005] Different synthesis methods of asenapine have been reported in the prior art. ...

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): C07D491/044C07D207/08
CPCY02P20/55C07D491/044C07D207/08
Inventor 郭德
Owner YANGPU HG PHARMA
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