New refining method of 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrryl-1-one

A technology of oxazol and 5-c, which is applied in the field of solvent selection and important intermediates of asenapine, and can solve the problems of low yield and the like

Inactive Publication Date: 2014-05-07
AVENTIS PHARMA HAINAN
View PDF4 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] 11-Chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxazo[4,5-c]pyrrole-1 is now reported - There are few post-processing and refining methods for ketones, such as the post-processing

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
  • New refining method of 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrryl-1-one
  • New refining method of 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrryl-1-one

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Implementation example 1: 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxazelo[4,5-c]pyrrole Synthesis of -1-ketone and the post-treatment method reported in the patent US4345434A

[0019] Add 11-chloro-2,3-dihydro-2-methyl-1H-dibenzo[2,3:6,7 ]oxazo[4,5-c]pyrrol-1-one 50g (0.168mol), then add 500 mL of methanol as a solvent, heat to reflux, add four iodine grains, add magnesium chips in small amounts and multiple times in batches 17.6g (0.729mol), reacted for 2.5h under the condition of heating to reflux and uninterrupted free radical initiation, sampling and dilution plate to monitor the reaction progress (developer PE:EA=1:1, color development under 254nm ultraviolet light). After the reaction of the raw materials is complete, stop heating, stir to cool down to room temperature, move to a 2L one-necked bottle to spin dry the solvent methanol, slowly add 1.6 L of 6 N hydrochloric acid in an ice-water bath, and stir for 30 minutes in an ice-water bath a...

Embodiment 2

[0020] Example 2: Methanol-ethyl acetate-water-hydrochloric acid system for 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxygen Post-treatment method of heterozo[4,5-c]pyrrol-1-one

[0021] Prepare 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxazepine[4, 5-c] Pyrrol-1-one, after the reaction of the raw materials is complete, stop heating, stir and cool down to room temperature, filter under reduced pressure (the filter cloth and sufficient amount of diatomaceous earth are placed in the Buchner funnel), and use 100 mL of diatomaceous earth for the filter cake. Wash the filter cake with 200 mL of ethyl acetate and stir for 30 min. Suction filtration under reduced pressure while hot, wash the filter cake with ethyl acetate, and spin dry the combined filtrate to obtain a light brown solid. Add 390 mL of distilled water, stir and disperse at 25 °C, and adjust the pH to 5 with 6 N aqueous hydrochloric acid. Suction filtration under reduced pressure, ...

Embodiment 3

[0022] Example 3: Methanol-water-sulfuric acid system for 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxazepine[ 4,5-c]pyrrol-1-one post-treatment method

[0023] Prepare 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxazepine[4, 5-c] Pyrrol-1-one, after the reaction of the raw materials is complete, stop heating, stir and cool down to room temperature, vacuum filter under reduced pressure (filter cloth and sufficient amount of diatomaceous earth are cushioned in the Buchner funnel), filter cake with 500 mL The methanol was dissolved in hot water and stirred for 30 min, then filtered under reduced pressure while hot, the filter cake was washed with methanol, and the combined filtrate was spin-dried to obtain a light yellow solid. Add 390 mL of distilled water, stir and disperse at 25 °C, and adjust the pH to 1 with 50% sulfuric acid aqueous solution. Suction filtration under reduced pressure, the filter cake was washed with distilled water, and ...

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 field of pharmaceutical chemistry, and relates to a refining method of an asenapine important intermediate 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrryl-1-one. The refining method is simple to operate, can easily implement industrial production, and enhances the yield by nearly 20% relative to reported documents.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to an important intermediate of asenapine: 11-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenzo[2,3:6,7 ] Oxazolo[4,5-c]pyrrol-1-one post-treatment method and solvent selection. Background technique [0002] Asenapine (English name asenapine, trade name SAPHRIS), chemical name is trans-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3: 6,7]oxazolo[4,5-c]pyrrole, which is a compound with CNS-inhibitor activity and antihistamine and antiserotonin activity (see US patent: US4145434A). Its structural formula is as follows: [0003] [0004] Asenapine was developed as its maleate salt. Asenapine maleate is a broad-spectrum and highly potent norepinephrine, serotonin, and dopamine antagonist, and its potential antipsychotic activity can be used in adults with schizophrenia, mania, or type I bipolar Emergency treatment of mixed episodes of affective disorder. Thi...

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): C07D491/044
CPCC07D491/044
Inventor 王梅王进敏魏赛马苏峰
Owner AVENTIS PHARMA HAINAN
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