Preparation method and product of venetoclax

A technology of venetoclax and chlorophenyl, applied in the field of medicine, can solve the problems of increasing the production cost of enterprises, reducing the yield of the target product, reducing the activity of the amino group, etc., improving the quality, being beneficial to large-scale industrial production, and having fewer synthesis steps. Effect

Inactive Publication Date: 2019-03-08
CHONGQING SANSHENG IND CO LTD
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] However, the defect of this synthetic method is that there are two amino groups in 3-nitro-4-((tetrahydro-2H-pyran-4-yl)methylamino)benzenesulfonamide, and sulfonamide is due to the The electron-withdrawing effect leads to a decrease in the activity of the amino group in sulfonamide, and although the aromatic amine is a secondary amine that has a certain steric effect, it still has ...

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 and product of venetoclax
  • Preparation method and product of venetoclax
  • Preparation method and product of venetoclax

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Step 1: 4-(4-{[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N -[(3-nitro-4-fluorophenyl)sulfonyl)]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide / 4-(4- {[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(3-nitro- Preparation of 4-chlorophenyl)sulfonyl)]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (Ⅲ)

[0037]

[0038] Compound (II) (20.0g, 35.0mmol) was dissolved in 300mL dichloromethane (DCM), and 3-nitro-4-fluorobenzenesulfonamide (8.5g, 38.5mmol), 4-di Methylaminopyridine (DMAP) (6.4 g, 52.5 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCL) (10.1 g, 52.5 mmol). Control the temperature at 20-30°C and stir the reaction for 16 hours. After completion of the reaction, add 100 mL of 5% acetic acid aqueous solution to wash once, and then wash once with 100 mL of water. The organic phase is dried with 20 g of sodium sulfate, filtered, and spin-dried to obtain 26.1 g of fluorine-containing c...

Embodiment 2

[0043] Step 1: 4-(4-{[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N -[(3-nitro-4-fluorophenyl)sulfonyl)]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide / 4-(4- {[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(3-nitro- Preparation of 4-chlorophenyl)sulfonyl)]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (Ⅲ)

[0044]

[0045] Compound (II) (20.0g, 35.0mmol) was placed in 300mL of dichloromethane (DCM), and 3-nitro-4-chlorobenzenesulfonamide (9.1g, 38.5mmol), 4-di Methylaminopyridine (DMAP) (6.4 g, 52.5 mmol), 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC.HCL) (10.1 g, 52.5 mmol). The temperature was controlled at 20-30° C. and stirred for 16 hours. TLC detection showed that the reaction of the raw materials was complete. After completion of the reaction, add 100 mL of 5% acetic acid aqueous solution to wash once, and then wash once with 100 mL of water. The organic phase is dried with 20 g of sodium ...

Embodiment 3

[0050] Step 1: 4-(4-{[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N -[(3-nitro-4-fluorophenyl)sulfonyl)]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide / 4-(4- {[2-(4-Chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazin-1-yl)-N-[(3-nitro- Preparation of 4-chlorophenyl)sulfonyl)]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide (Ⅲ)

[0051]

[0052] Compound (Ⅱ) (20.0g, 35.0mmol) was dissolved in 100mL N,N-dimethylformamide (DMF), and 3-nitro-4-fluorobenzenesulfonamide (8.5g, 38.5mmol) was added successively at room temperature ), 1-hydroxybenzotriazole (HOBt) (7.1 g, 52.5 mmol), N,N'-diisopropylcarbodiimide (DIC) (6.6 g, 52.5 mmol). Control the temperature at 10-20° C. and stir the reaction for 12 hours. TLC detection shows that the reaction of the raw materials is complete. After the reaction is completed, add 300 mL of dichloromethane to mix, then add 100 mL of 1% acetic acid aqueous solution to wash once, the organic phase is washed onc...

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

A preparation method of venetoclax comprises the following steps: dissolving 2-[(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy]-4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl]methyl]piperazin-1-yl]benzoicacid and 4-fluoro-3-nitrobenzenesulfonamide/4-chloro-3-nitrobenzenesulfonamide in a solvent, and performing a condensation reaction and separation to obtain 4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl-1-yl]methyl]piperazin-1-yl])-N-[(3-nitro-4-fluoro(or chloro)phenyl) sulfonyl)]-2-(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy) benzamide; performing a substitution reaction on 4-(4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-enyl-1-yl]methyl]piperazin-1-yl])-N-[(3-nitro-4-fluoro(or chloro)phenyl) sulfonyl)]-2-(1H-pyrrolo[2,3-b]pyridin-5-yl)oxy) benzamide and 4-(aminomethyl)tetrahydro-2H-pyran, and performing separation and refining to obtain venetoclax.

Description

technical field [0001] The invention relates to the field of medicine, in particular to a preparation method of venetura and its product. Background technique [0002] The chemical name of Venetola is 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1-yl]methyl}piperazine-1- Base)-N-({3-nitro-4-[(tetrahydro-2H-pyran-4-ylmethyl)amino]phenyl}sulfonyl)-2-(1H-pyrrolo[2,3 -b]pyridin-5-yloxy)benzamide, which is the first selective inhibitor targeting B-cell lymphoma factor 2 (BCL-2). B-cell lymphoma factor 2 (B-celllymphoma-2, BCL-2) in the cells of leukemia patients can promote the growth of cancer cells, and it is often overexpressed in B lymphocytes and other B-cell malignancies. It was published on April 11, 2016 FDA approved listing for chronic lymphocytic leukemia. [0003] There are many routes for the synthesis of venetura, but in the prior art, each synthetic route will obtain the same intermediate 2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)- 4-(4-((2-(4-chlorophenyl)-4,4...

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): C07D471/04
CPCC07D471/04
Inventor 彭磊黄雄鸠何伟唐丽昌柳玲陈振明
Owner CHONGQING SANSHENG IND CO LTD
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