CN103992274A - Method for synthesizing selective non-steroidal anti-inflammatory and analgesic Celebrex - Google Patents

Method for synthesizing selective non-steroidal anti-inflammatory and analgesic Celebrex Download PDF

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Publication number
CN103992274A
CN103992274A CN201410157853.6A CN201410157853A CN103992274A CN 103992274 A CN103992274 A CN 103992274A CN 201410157853 A CN201410157853 A CN 201410157853A CN 103992274 A CN103992274 A CN 103992274A
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China
Prior art keywords
compound
celebrex
steroidal anti
condition
inflammatory
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CN201410157853.6A
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Chinese (zh)
Inventor
王小龙
邵志强
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Nanjing An Mei Science And Technology Ltd
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Nanjing An Mei Science And Technology Ltd
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Priority to CN201410157853.6A priority Critical patent/CN103992274A/en
Publication of CN103992274A publication Critical patent/CN103992274A/en
Pending legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a method for synthesizing a selective non-steroidal anti-inflammatory and analgesic Celebrex. The method is characterized in that Celebrex with the chemical name of 4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1-hydro-pyrazol-1-yl]benzenesulfonamide is synthesized at room temperature by adopting a compound 1 and a compound 2 as raw materials, lithium hydroxide as an alkali and ethylene glycol dimethyl ether as a solvent. The method has the advantages of simple operation, mild reaction conditions and high yield, and is a new effective Celebrex synthesis method.

Description

The method of synthesis of selective non_steroidal anti_inflammatory drug Celebrex (celecoxib)
Technical field
The present invention relates to field of medicine and chemical technology, be specifically related to the synthetic method of a kind of selectivity non_steroidal anti_inflammatory drug Celebrex (celecoxib).
Background technology
Celecoxib (Celecoxib, 1) is the COX-2 selective depressant of first listing, its chemistry 4-[5-(4-aminomethyl phenyl)-3-(trifluoromethyl)-1-hydrogen-pyrazol-1-yl by name] benzsulfamide, by Searle company, developed.By selectivity, suppress cyclooxygenase-2 (COX-2) and suppress prostaglandin(PG) generation, reach anti-inflammatory, analgesic effect.Because it can not suppress to have the physiology enzyme of pipe intestinal protection effect--cyclooxygenase-1 (COX-1), gastrointestinal side effect risk is starkly lower than traditional non_steroidal anti_inflammatory drug.Therefore, this medical instrument has gi tract and the advantage such as Toxicity of Kidney is little, is mainly used in the treatment of the diseases such as rheumatic arthritis and osteoarthritis, is called as super acetylsalicylic acid.
At present about the synthetic method of celecoxib, mainly contain the synthetic method (equation as shown in Figure 2) of US5521207 and WO2003024400 (equation as shown in Figure 3) etc.
Accompanying drawing explanation
Fig. 1 is a kind of celecoxib synthetic method equation designing in the present invention.
Fig. 2 is celecoxib synthetic method equation in US5521207.
Fig. 3 is celecoxib synthetic method equation in WO2003024400.
Concrete operations are implemented
To filling in the flask of glycol dimethyl ether (7mL), add compound 1 (626mg, 1.0mmol) and compound 2 (760mg, 2.0mmol).Complete molten after, add lithium hydroxide (70mg, 2.7mmol).Reaction is at stirring at room 12h.HPLC detects raw material 1 and disappears, and reacts completely.Concentration of reaction solution, crosses the separated (elutriant: heptane/ethyl acetate=1: 1), obtain 210mg white solid product, productive rate 77% (equation as shown in Figure 1) of post.
1H?NMR(300MHz，DMSO-d 6)：7.88(dt，J＝8.8，J＝2.3，2H)，7.76(dd，J＝8.7，2.3，2H)，7.72(s，2H)，7.29-7.13(m，7H)，2.32(s，3H)，MS(m/z)for?MH +(C 17H 16F 3N 3O 2S)：caic：382.0837；found：382.1。

Claims (5)

1. the present invention relates to the synthetic method of a kind of non_steroidal anti_inflammatory drug Celebrex (celecoxib), its synthetic method is that to take compound 1 and compound 2 be raw material, is dissolved in suitable organic solvent, and mineral alkali is done alkali, under room temperature condition, aftertreatment obtains target product.
2. method according to claim 1, is characterized in that compound 1 and compound 2 material molar ratios are 1.0: 1.0; 1.0: 1.5; 1.0: 2.0; 1.0: 2.5; 1.0: 3.0 etc., its more excellent condition was second 1.0: 2.0.
3. the method for weighing according to claim 1, is characterized in that its organic solvent used can be acetonitrile, acetone, and Isosorbide-5-Nitrae-dioxane, tetrahydrofuran (THF) etc., it is glycol dimethyl ether compared with enemy condition.
4. the method for claim 1, is characterized in that its mineral alkali used can be sodium hydroxide, calcium hydroxide, and potassium hydroxide, and lithium hydroxide, its more excellent condition is lithium hydroxide.
5. the method for claim 1, is characterized in that selecting under room temperature condition and reacts, and the reaction times can be 4h, 8h, and 12h, 16h, 24h, its more excellent condition is 12h.
CN201410157853.6A 2014-04-18 2014-04-18 Method for synthesizing selective non-steroidal anti-inflammatory and analgesic Celebrex Pending CN103992274A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410157853.6A CN103992274A (en) 2014-04-18 2014-04-18 Method for synthesizing selective non-steroidal anti-inflammatory and analgesic Celebrex

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410157853.6A CN103992274A (en) 2014-04-18 2014-04-18 Method for synthesizing selective non-steroidal anti-inflammatory and analgesic Celebrex

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CN103992274A true CN103992274A (en) 2014-08-20

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105753783A (en) * 2016-04-08 2016-07-13 李文淏 Method for synthesizing celecoxib

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003024400A2 (en) * 2001-09-18 2003-03-27 Onconova Therapeutics, Inc. Process for the preparation of 1,5-diarylpyrazoles
WO2003024958A2 (en) * 2001-09-18 2003-03-27 Onconova Therapeutics, Inc. Processes for the preparation of 1,5-diaryl-3-substituted-pyrazoles
CN101084194A (en) * 2004-12-21 2007-12-05 默克公司 Mitotic kinesin inhibitors
CN103102306A (en) * 2013-02-06 2013-05-15 河南东泰制药有限公司 Preparation method for celecoxib

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003024400A2 (en) * 2001-09-18 2003-03-27 Onconova Therapeutics, Inc. Process for the preparation of 1,5-diarylpyrazoles
WO2003024958A2 (en) * 2001-09-18 2003-03-27 Onconova Therapeutics, Inc. Processes for the preparation of 1,5-diaryl-3-substituted-pyrazoles
CN101084194A (en) * 2004-12-21 2007-12-05 默克公司 Mitotic kinesin inhibitors
CN103102306A (en) * 2013-02-06 2013-05-15 河南东泰制药有限公司 Preparation method for celecoxib

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
AIXUE SUN ET AL: "A new efficient synthesis of pyrazoles from hydrazonoyl halides and β-oxophosphonates", 《TETRAHEDRON LETTERS》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105753783A (en) * 2016-04-08 2016-07-13 李文淏 Method for synthesizing celecoxib
CN105753783B (en) * 2016-04-08 2017-12-15 李文淏 A kind of method for synthesizing celecoxib

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Application publication date: 20140820