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Preparation method of high-yield and high-purity celecoxib

A celecoxib, high-purity technology is applied in the field of preparation of high-yield and high-purity celecoxib, and achieves the effects of simple process, easy large-scale production, and improved yield and purity.

Active Publication Date: 2013-04-17
山东诚汇双达药业有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the operation is complicated, and sodium alkoxide needs to be prepared, which has certain risks; 1-p-methylphenyl-4,4,4-trifluoro-1,3-butanedione needs to be processed out of the system, which affects the yield ; Moreover, the reaction time is long, the temperature is high (reflux), and side reactions are prone to occur
It is also the same problem in the preparation of celecoxib, the reaction temperature is high, the time is long, and the handling is troublesome

Method used

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  • Preparation method of high-yield and high-purity celecoxib
  • Preparation method of high-yield and high-purity celecoxib

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0052] Preparation: Add 48.24g of sodium methoxide solution (0.134mol sodium methoxide) to a 250ml three-necked flask, add 19g (0.134mol) of ethyl trifluoroacetate, stir for several minutes, then add 13.5g (0.1mol) of p-methylacetophenone, Heat to 60±3°C for 5 hours to obtain a solution of the intermediate 1-p-methylphenyl-4,4,4-trifluoro-1,3-butanedione, which is set aside.

[0053] Add 23g (0.103mol) of p-hydrazinobenzenesulfonamide hydrochloride, 41.4g of methanol, 27.6g of water, and 11.33g (0.113mol) of hydrochloric acid into a 1000ml three-neck flask, stir, and heat to 60±3°C.

[0054] Add the reaction solution of the obtained intermediate 1-p-methylphenyl-4,4,4-trifluoro-1,3-butanedione dropwise to the solution of p-hydrazinobenzenesulfonamide hydrochloride, and dropwise , 60±3°C for 3 hours, a large amount of off-white solid precipitated. Natural cooling and crystallization for about 12 hours. Filter, wash thoroughly with 50% methanol water, and dry at 60°C for 6 hou...

Embodiment 2

[0057]Preparation: Add 73.3g of sodium isopropoxide solution (0.134mol sodium isopropoxide) into a 250ml three-necked flask, add 19g (0.134mol) of ethyl trifluoroacetate, stir for several minutes, then add 13.5g of p-methylacetophenone ( 0.1mol), heated to 60±3°C and reacted for 5 hours to obtain a solution of the intermediate 1-p-methylphenyl-4,4,4-trifluoro-1,3-butanedione, which was set aside.

[0058] Add 23g (0.103mol) of p-hydrazinobenzenesulfonamide hydrochloride, 41.4g of isopropanol, 27.6g of water, and 11.33g (0.113mol) of hydrochloric acid into a 1000ml three-neck flask, stir, and heat to 60±3°C.

[0059] Add the reaction solution of the obtained intermediate 1-p-methylphenyl-4,4,4-trifluoro-1,3-butanedione dropwise to the solution of p-hydrazinobenzenesulfonamide hydrochloride, and dropwise , 60±3°C for 3 hours, a large amount of off-white solid precipitated. Natural cooling and crystallization for about 12 hours. Filter, wash thoroughly with 50% isopropanol wate...

Embodiment 3

[0062] Preparation: Add 60.76g (0.134mol sodium ethoxide) of sodium ethoxide solution to a 250ml three-necked flask, add 19g (0.134mol) of ethyl trifluoroacetate, stir for several minutes, then add 13.5g (0.1mol) of p-methylacetophenone, Heat to 60±3°C for 5 hours to obtain a solution of the intermediate 1-p-methylphenyl-4,4,4-trifluoro-1,3-butanedione, which is set aside.

[0063] Add 23g (0.103mol) of p-hydrazinobenzenesulfonamide hydrochloride, 41.4g of ethanol, 27.6g of water, and 11.33g (0.113mol) of hydrochloric acid into a 1000ml three-neck flask, stir, and heat to 60±3°C.

[0064] Add the reaction solution of the obtained intermediate 1-p-methylphenyl-4,4,4-trifluoro-1,3-butanedione dropwise to the solution of p-hydrazinobenzenesulfonamide hydrochloride, and dropwise , 60±3°C for 3 hours, a large amount of off-white solid precipitated. Natural cooling and crystallization for about 12 hours. Filter, wash thoroughly with 50% ethanol water, and dry at 60°C for 6 hours t...

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Abstract

The invention belongs to the technical field of preparation methods of drugs, and particularly relates to a preparation method of high-yield and high-purity celecoxib. The preparation method of the high-yield and high-purity celecoxib comprises the following steps: preparing a salt solution of 1-p-methylphenyl-4,4,4-trifluoro-1,3-butanedione, preparing an alcohol water solution of hydrazinobenzene-1-sulfonamide hydrochloride, conducting reaction, drying, and refining. The preparation method has the benefits that compared with the traditional method, with the adoption of the preparation method of the celecoxib, the yield and purity are increased; the yield of the celecoxib reaches above 91%; the purity reaches above 99%; and the method is simple in technology, and can be applied to large-scale production easily.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation methods, and in particular relates to a preparation method of high-yield and high-purity celecoxib. Background technique [0002] Celecoxib (Celecoxib), the chemical name is 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide, the molecular formula is C 17 h 14 f 3 N 3 o 2 S, molecular weight 381.37, structural formula is [0003] [0004] Celecoxib is a first-generation specific CO X -2 Inhibitor, anti-arthritic drug, less gastrointestinal side effects, used for treating arthritis, anti-inflammatory, analgesic, relieving symptoms and signs of osteoarthritis and rheumatoid arthritis. Synthetic methods disclosed in the literature [0005] [0006] The raw materials of this route are easy to obtain and cheap, and are more suitable for industrial production. However, the operation is complicated, and sodium alkoxide needs to be prepared, which has...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D231/12
Inventor 于东海王素兰杨彦军王庭见
Owner 山东诚汇双达药业有限公司
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