Celecoxib and preparing method thereof

A technology of celecoxib and methylphenyl, which is applied in the direction of organic chemistry, can solve the problems of complicated purification steps and high impurity content, and achieve the effect of reducing content and improving product quality

Active Publication Date: 2012-07-11
广东暨大基因药物工程研究中心有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The purpose of the present invention is to provide celecoxib and its preparation method, to solve the technical prob

Method used

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preparation example Construction

[0026] The apparent 4-halobenzenesulfonamides can be prepared by conventional methods. The preparation method of conventional 4-halobenzenesulfonamide can be following method, and this method comprises the following steps:

[0027] 1) Add sulfonamide to the hydrogen halide, cool to -5-0°C, add sodium nitrite aqueous solution dropwise, continue stirring for 0.5-1.5 hours, then add copper halide hydrogen halide solution dropwise to obtain a mixture;

[0028] 2) The mixture was heated in a water bath to 75-80° C. for 2 h to obtain 4-halobenzenesulfonamide.

Embodiment 1

[0037] 1. Synthesis of 4-bromobenzenesulfonamide

[0038] Add 72ml 40% HBr into a 500ml two-necked bottle, slowly add 34.41g (0.02mol) sulfonamide under stirring, cool to -5-0°C, slowly add 25ml aqueous solution of 14.0g (0.02mol) sodium nitrite dropwise. After the dropwise addition was completed, stirring was continued at this temperature for 1 h. Add this solution dropwise to 28.7g (0.02mol) CuBr in 35ml 40% HBr solution under ice-cooling, when the gas is generated slowly, heat up to 80°C, react for 2h, add 100ml of water, stir at room temperature for 5h, filter , washed with water, dried in vacuo, and the crude product was recrystallized from ethyl acetate / petroleum ether to obtain an off-white solid, 33.1g, yield 70.0%, m.p.165-166°C.

[0039] 2. Synthesis of 5-(4-methylphenyl)-3-trifluoromethyl-1H-pyrazole

[0040] Mix 3.13g of 80% hydrazine hydrate (50mmol) with 11.5g (50mmol) of 1-(4-methylphenyl)-4,4,4-trifluoro-1,3-butanedione and 60ml of methanol, and heat to reflu...

Embodiment 2

[0044] The difference with Example 1 is that when synthesizing celecoxib, the base used is K 3 PO 4 (2.1 equiv), the reaction temperature is 110° C., the reaction time is 6 hours, and the yield of the synthesized celecoxib is 68.1%. After HPLC detection, it can be seen that the regioisomer content is 0.01%.

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Abstract

The invention provides celecoxib and a preparing method thereof. The preparing method of the celecoxib comprises the following steps: mixing 5- (4-methylphenyl) -3-trifluoromethyl-1H-pyrazole and 4-halogen benzene sulfonamide, then dissolving the mixture in the second organic solvent, and then adding alkali and catalyst to obtain the celecoxib after coupling reactions. The 5-(4-methylphenyl) -3-(trifluoromethyl)- 1H-pyrazole:(1) is prepared according to the following procedures: mixing dissolving 1-(4- methylphenyl) -4, 4, 4-trifluoro1, 3-butanedione and hydrazine hydrate in the second organic solvent, then obtaining 5-(4-methylphenyl)-3-(trifluoromethyl)-1H-crude pyrazole after heating and dehydration cyclization reaction; (2), obtaining 5-(4-methylphenyl) -3- (trifluoromethyl)-1H-pyrazole by purifying the crude pyrazole. The preparing method provide by the invention can effectively reduce the content of regional isomers in celecoxib, and dramatically improve the quality of products. The productivity can reach 81.3%, and the content of the regional isomer is 0.01%.

Description

technical field [0001] The invention relates to the field of celecoxib production, in particular to a preparation method of celecoxib. In addition, the present invention also relates to a kind of celecoxib prepared by the above method. Background technique [0002] Celecoxib is a new type of anti-inflammatory drug for the treatment of rheumatoid arthritis and osteoarthritis, which can specifically act on COX-2 (type II cyclooxyesterase), and its chemical name is 4-[5 -(4-methylphenyl)-3-(trifluoromethyl)-1-hydro-pyrazol-1-yl]benzenesulfonamide was developed by Seale Pharmaceuticals, USA. The drug avoids the problem that traditional non-steroidal anti-inflammatory drugs are prone to produce severe gastrointestinal side effects due to the simultaneous inhibition of COX-1 (type I cyclooxyesterase), and has been rapidly applied worldwide after being marketed. [0003] Regarding the synthesis of celecoxib, WO97 / 11704 discloses its synthetic method, carries out Claison condensat...

Claims

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Application Information

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IPC IPC(8): C07D231/12
Inventor 张庆华徐广宇
Owner 广东暨大基因药物工程研究中心有限公司
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