CN103923011A - Synthetic method of celecoxib - Google Patents
Synthetic method of celecoxib Download PDFInfo
- Publication number
- CN103923011A CN103923011A CN201410183964.4A CN201410183964A CN103923011A CN 103923011 A CN103923011 A CN 103923011A CN 201410183964 A CN201410183964 A CN 201410183964A CN 103923011 A CN103923011 A CN 103923011A
- Authority
- CN
- China
- Prior art keywords
- celecoxib
- reaction
- toluene
- synthetic method
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- MPVPOTMPKLOUHZ-UHFFFAOYSA-N Cc1cccc(-c2cc(C(F)(F)F)n[n]2-c(cc2)ccc2S(N)(=O)=O)c1 Chemical compound Cc1cccc(-c2cc(C(F)(F)F)n[n]2-c(cc2)ccc2S(N)(=O)=O)c1 MPVPOTMPKLOUHZ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthetic method of celecoxib. The synthetic method is characterized by comprising the following steps: firstly, adding sodium methylate as an aldol condensation catalyst and methylbenzene as a reaction solvent into a reaction container, adding p-methylacetophenone and trifluoroacetic acid ethyl ester, fully reacting, adding diluted hydrochloric acid, and separating out a water layer to obtain a methylbenzene solution of an intermediate-diketone; secondly, adding water, a phase transfer catalyst and 4-aminosulfophenyl hydrazine hydrochloride into the methylbenzene solution of the intermediate-diketone, and performing dehydration cyclization reaction to obtain a celecoxib reaction solution; thirdly, replenishing methylbenzene, standing, separating out the water layer and remaining an organic layer; cooling the organic layer, preserving heat and crystallizing to obtain a crystal product, and performing suction filtration, methylbenzene washing and water washing in sequence to obtain a celecoxib crude product; drying the crude product in vacuum, decolorizing and re-crystallizing to obtain a celecoxib raw material. According to the synthetic method, the celecoxib yield is increased, the reaction time is shortened, the celecoxib purity is high, the three-waste discharge in the whole production process is reduced, and the production cost is low.
Description
Technical field
The invention belongs to pharmaceutical chemistry technical field, be specifically related to a kind of synthetic method of Celecoxib.
Background technology
Celecoxib is to be gone on the market in December, 1998 by Pfizer, it is first cyclooxygenase-2, the whole world (the English COX-2 of abbreviation) inhibitor, this class medicine is in the lenitive while, the serious gastrointestinal side effect that can avoid NSAID (non-steroidal anti-inflammatory drug) in the past to bring, the molecular formula of Celecoxib is C
17h
14f
3n
3o
2s, molecular weight is 381.37, its chemical structural formula as shown in Equation 1:
At present only one, the route of industrial synthetic Celecoxib is all that in different alkali and organic solvent, intermediate diketone is produced in condensation taking p-methyl aceto phenone and Trifluoroacetic Acid Ethyl Ester as raw material.And then produce Celecoxib from 4-amine sulfo group hydrazinobenzene hydrochloride salt dehydration condensation in different solvent systems.
First Pfizer has reported the synthesis technique of Celecoxib in patent WO9637476.From p-methyl aceto phenone and Trifluoroacetic Acid Ethyl Ester, first in the organic solvents such as highly basic and the tertiary ether of first or toluene, condensation generates intermediate diketone.This intermediate obtains product with 4-amine sulfo group hydrazinobenzene hydrochloride salt dehydration condensation in ethanol and hydrochloric acid.But the ethanol that this patent second step adopts and hydrochloric acid system inconvenient actual production.Due to ethanol and water miscible mutually, be unfavorable for reclaim.In addition, the purity certificate of the crude product impurity B that this technique obtains below document Org.Process Res.Dev. is reported in 2% left and right, and such crude product generally needs twice recrystallization to process just reach pharmacopeia requirement.Patent US2008234491 has reported taking p-methyl aceto phenone and Trifluoroacetic Acid Ethyl Ester as raw material and has reacted in sodium methylate and toluene, generated intermediate diketone.This intermediate diketone and 4-amine sulfo group hydrazinobenzene hydrochloride salt react the technique of producing Sai Laixibu in the system of ethyl acetate and water subsequently.Because two-step reaction adopts different solvent systems, in aftertreatment, toluene and ethyl acetate all need to concentrate, and have increased the consumption of solvent.In addition, because product solubleness in ethyl acetate is very large, can not carry out therein recrystallization processing, gained crude product purity is generally in 95% left and right, and the content of impurity A (chemical name: 4-[5-(3-tolyl)-3-(trifluoromethyl)-1-pyrazolyl] benzsulfamide) and impurity B (4-[3-(4-tolyl)-5-(trifluoromethyl)-1-pyrazolyl] benzsulfamide) is 2%.Wherein, the chemical structural formula of impurity A is as follows:
The chemical structural formula of impurity B is as follows:
We through test of many times find this crude product must twice recrystallization just can obtain meeting the Sai Laixibu of pharmacopeia quality.To sum up all uneconomical environmental protection of above-mentioned two techniques.
In addition, document Org.Process Res.Dev.2009,13, in 98., reported the shrink technique of cyclization of intermediate diketone in toluene and water, but due to product and 4-amine sulfo group hydrazinobenzene hydrochloride salt solubleness in toluene very low, reaction effect is very poor, thick yield low enter ethyl acetate and aqueous systems 8%, and impurity B is up to 3%.Such crude product is difficult to obtain meeting by recrystallization the product that will put purity.
Summary of the invention
The object of the present invention is to provide a kind of synthetic method of Celecoxib, bring recrystallization often to overcome two step synthetic route methods in above-mentioned prior art, production cycle is long, solvent system complexity, solvent recuperation is more difficult, the high deficiency of production cost, drops to minimum level by the production cost of this Celecoxib product and environmental hazard.
For achieving the above object, the technical solution used in the present invention is: a kind of synthetic method of Celecoxib, and described synthetic method comprises the following steps:
The first step, to adding in reaction vessel as the sodium methylate of aldol condensation catalyst with as the toluene of reaction solvent, add again raw material p-methyl aceto phenone and Trifluoroacetic Acid Ethyl Ester, stir, after fully reacting, in reaction system, add dilute hydrochloric acid with termination reaction again, after point water-yielding stratum, obtain the toluene solution of intermediate diketone;
Wherein, the mol ratio of described p-methyl aceto phenone, Trifluoroacetic Acid Ethyl Ester and sodium methylate is 1:1～1.3:1.1～1.5, and the volume ratio of p-methyl aceto phenone and toluene is 1:3～10;
Second step adds water, phase-transfer catalyst and 4-amine sulfo group hydrazinobenzene hydrochloride salt to carry out dehydration condensation reaction in the toluene solution of described intermediate diketone, makes Celecoxib reaction solution;
Wherein, described phase-transfer catalyst is selected from any one in tetrabutylammonium chloride, Tetrabutyl amonium bromide, benzyltriethylammoinium chloride and Dodecyl trimethyl ammonium chloride; The volume that adds described water is 0.5～1 times of toluene solution volume of described intermediate diketone; The mol ratio of described p-methyl aceto phenone and described phase-transfer catalyst is 1:0.005～0.05; The mol ratio of described 4-amine sulfo group hydrazinobenzene hydrochloride salt and intermediate diketone is 0.9～1.2:1;
The 3rd step, adds toluene in the Celecoxib reaction solution making to described second step, under 20 DEG C～70 DEG C conditions, and point water-yielding stratum after leaving standstill and retain organic layer, wherein, the amount of adding toluene is 2～4 times of volume of toluene in the described the first step;
Described organic layer is cooled to 0 DEG C～30 DEG C again, after insulation crystallization, obtains crystallization product, then carry out successively suction filtration, toluene wash, washing, obtains Celecoxib crude product;
By the vacuum-drying 3～8 hours at 30 DEG C～70 DEG C of described Celecoxib crude product, and then with the aqueous ethanolic solution that volumetric concentration is 40～60% recrystallization that decolours, obtain Celecoxib bulk drug.
Related content in technique scheme is explained as follows:
1,, in such scheme, preferably scheme is that the temperature of reaction of described dehydration condensation reaction is 30 DEG C～90 DEG C, keeps reaction 5～24 hours.
2,, in such scheme, preferably scheme is in described the 3rd step, in the aqueous ethanolic solution that is 40～60%, adds gac with the recrystallization that decolours to described volumetric concentration.
3, in such scheme, it is solvent that two-step reaction all adopts toluene, and the toluene solution of the first step product diketone does not need dry concentrated, directly enters next step.
4,, in such scheme, described intermediate diketone is the fluoro-1-of 4,4,4-tri-(4-tolyl)-1,3-dimethyl diketone.
Principle of the present invention and beneficial effect: chemical equation of the present invention is as follows:
Wherein, be Celecoxib in above chemical equation Chinese style 1, formula 2 is p-methyl aceto phenone, and formula 3 is Trifluoroacetic Acid Ethyl Ester, and formula 4 is intermediate diketone, and formula 5 is 4-amine sulfo group hydrazinobenzene hydrochloride salt.
The present invention has added phase-transfer catalyst, has increased raw material and the product solubleness in reaction system, and product yield improves, and the reaction times shortens; At two step chemical reactions of the present invention, all taking toluene as solvent, and toluene solvant all do not need to concentrate, and can directly enter next step operation; Toluene solvant also has the effect of recrystallization to Celecoxib crude product in the present invention, crude product carries out crystallization and purification after producing in reaction solvent toluene, be equivalent to save a step recrystallization operation, simple to operate, products obtained therefrom purity is high, impurity B content obviously reduces, and gained Celecoxib bulk drug meets US and European pharmacopeia.Whole production technique three waste discharge reduces, and solvent recovery effect is good, and the production cycle shortens, and production cost is low.Embodiment
The invention will be further described for embodiment below:
Embodiment mono-: a kind of synthetic method of Celecoxib
1L four-hole reaction flask, make-up machinery stirs, water-bath.Under nitrogen protection, first add wherein 12.8g sodium methylate, 200ml industrial toluene.In controlling, temperature is no more than 40 DEG C, drips 30g Trifluoroacetic Acid Ethyl Ester.After dripping off, be cooled to 30 DEG C of left and right, drip 25g p-methyl aceto phenone, now not heat release.Under room temperature, stir 1h, be warming up to gradually subsequently 110 DEG C of reactions about 5 hours, middle control checks that p-methyl aceto phenone content is less than 1%, i.e. stopped reaction.After reaction finishes, in reaction solution, add the 3N hydrochloric acid soln of 100ml to regulate pH to 2, stir 10 minutes to organic layer clarification, stratification; 50ml toluene extraction for water layer, merges organic layer 60ml water washing once.
Above-mentioned toluene solution is transferred in 2 liters of reaction flasks, added wherein 250ml water, 1.0g tetrabutylammonium chloride, 43g4-amine sulfo group hydrazinobenzene hydrochloride salt, is heated to reflux 85 DEG C and reacts 6h, takes a sample to check, and intermediate diketone purity is less than 1%, finishes reaction.
In reaction solution, add 600ml toluene, be warming up to 65 DEG C, product dissolves.Leave standstill a point water-yielding stratum, organic layer crystallisation by cooling.Product, through suction filtration toluene wash, after washing, is dried, and obtains 60.3 grams of Celecoxib crude products.
In above-mentioned crude product, add 500 milliliters of dehydrated alcohols, heating for dissolving.Add again 0.7 gram of gac, 70 DEG C of stir abouts 0.5 hour, filtered while hot, filtrate heated and stirred, 80 DEG C progressively add 500 ml deionized water, crystallisation by cooling, suction filtration, 50% washing with alcohol, vacuum-drying, obtains 55 grams of Celecoxib finished products, productive rate: 78%.Purity 99.7%, impurity A 0.085%, impurity B: 0.093%.M/S?m/z379.9(M-)；1H?NMR(DMSO-d6)&7.88(d,J＝8.8Hz,2H),7.54(d,J＝8.8Hz,2H),7.50(s,2H),7.22(m,4H),7.17(s,1H),2.32(s,3H)。
Embodiment bis-: a kind of synthetic method of Celecoxib
1L four-hole reaction flask, make-up machinery stirs, water-bath.Under nitrogen protection, add 12.5g sodium methylate, 200ml industrial toluene.In controlling, temperature is no more than 40 DEG C, drips 30g Trifluoroacetic Acid Ethyl Ester.After dripping off, be cooled to 30 DEG C of left and right, drip 25g p-methyl aceto phenone, after adding, under room temperature, stir 1h.Be warming up to gradually 110 DEG C of reactions about 3 hours, middle control checks that p-methyl aceto phenone content is less than 1%, i.e. stopped reaction.After reaction finishes, in reaction solution, add the 3N hydrochloric acid soln of 100ml to regulate pH to 2, stir 10 minutes to organic layer clarification, stratification; 50ml toluene extraction for water layer, merges organic layer 60ml water washing once.
Above-mentioned toluene solution is transferred in 2 liters of reaction flasks, added wherein 150ml water, 0.7g Tetrabutyl amonium bromide, 43g4-amine sulfo group hydrazinobenzene hydrochloride salt, is heated to reflux 85 DEG C and reacts 10h, takes a sample to check, and intermediate diketone purity is less than 1%, finishes reaction.
In reaction solution, add 650ml toluene, be warming up to 65 DEG C, product dissolves.Leave standstill a point water-yielding stratum, organic layer crystallisation by cooling.Product, through suction filtration toluene wash, after washing, is dried, and obtains 52 grams of Celecoxib crude products.
In above-mentioned crude product, add 560 milliliters of dehydrated alcohols, heating for dissolving.Add again 0.7 gram of gac, 70 DEG C of stir abouts 0.5 hour, filtered while hot, filtrate heated and stirred, 80 DEG C progressively add 560 ml deionized water, crystallisation by cooling, suction filtration, 50% washing with alcohol, vacuum-drying, obtains 43.1 grams of productive rates of Celecoxib finished product: 61%.Purity 99.71%, impurity A 0.14%, impurity B: 0.089%.Mass spectrum is consistent with example 1 with nucleus magnetic hydrogen spectrum data.
Embodiment tri-: a kind of synthetic method of Celecoxib
1L four-hole reaction flask, make-up machinery stirs, water-bath.Under nitrogen protection, add 12.5g sodium methylate, 200ml industrial toluene.In controlling, temperature is no more than 40 DEG C, drips 31g Trifluoroacetic Acid Ethyl Ester.After dripping off, be cooled to 30 DEG C of left and right, drip 25g p-methyl aceto phenone, after adding, under room temperature, stir 1h.Be warming up to gradually 110 DEG C of reactions about 3 hours, middle control checks that p-methyl aceto phenone content is less than 1%, i.e. stopped reaction.After reaction finishes, in reaction solution, add the 3N hydrochloric acid soln of 100ml to regulate pH to 2, stir 10 minutes to organic layer clarification, stratification; 50ml toluene extraction for water layer, merges organic layer 60ml water washing once.
Above-mentioned toluene solution is transferred in 2 liters of reaction flasks, added wherein 150ml water, 0.9g Dodecyl trimethyl ammonium chloride, 43g sulfanilamide (SN) phenylhydrazine, is heated to reflux 85 DEG C and reacts 10h, takes a sample to check, and intermediate diketone purity is less than 1%, finishes reaction.
In reaction solution, add 650ml toluene, be warming up to 65 DEG C, product dissolves.Leave standstill a point water-yielding stratum, organic layer crystallisation by cooling.Product, through suction filtration toluene wash, after washing, is dried, and obtains 59 grams of Celecoxib crude products.
In above-mentioned crude product, add 450 milliliters of dehydrated alcohols, heating for dissolving.Add again 1.0 grams of gacs, 70 DEG C of stir abouts 0.5 hour, filtered while hot, filtrate heated and stirred, 80 DEG C progressively add 450 ml deionized water, crystallisation by cooling, suction filtration, 50% washing with alcohol, vacuum-drying, obtains 53.8 grams of productive rates of Celecoxib finished product: 75%.Purity 99.87%, impurity A 0.065%, impurity B: 0.058%.Mass spectrum is consistent with example 1 with nucleus magnetic hydrogen spectrum data.
Embodiment tetra-: a kind of synthetic method of Celecoxib
1L four-hole reaction flask, make-up machinery stirs, water-bath.Under nitrogen protection, add 30.2g sodium methylate, 300ml industrial toluene.In controlling, temperature is no more than 40 DEG C, drips 53g Trifluoroacetic Acid Ethyl Ester.After dripping off, be cooled to 30 DEG C of left and right, drip 50g p-methyl aceto phenone, after adding, under room temperature, stir 1h.Be warming up to gradually 110 DEG C of reactions about 3 hours, middle control checks that p-methyl aceto phenone content is less than 1%, i.e. stopped reaction.After reaction finishes, in reaction solution, add the 3N hydrochloric acid soln of 250ml to regulate pH to 2, stir 10 minutes to organic layer clarification, stratification; 100ml toluene extraction for water layer, merges organic layer 150ml water washing once.
Above-mentioned toluene solution is transferred in 3 liters of reaction flasks, added wherein 200ml water, 4.0g benzyltriethylammoinium chloride, 85g4-amine sulfo group hydrazinobenzene hydrochloride salt, is heated to reflux 70 DEG C and reacts 24h, takes a sample to check, and intermediate diketone purity is less than 1%, finishes reaction.
In reaction solution, add 1500ml toluene, be warming up to 65 DEG C, product dissolves.Leave standstill a point water-yielding stratum, organic layer crystallisation by cooling.Product, through suction filtration toluene wash, after washing, is dried, and obtains approximately 110 grams of Celecoxib crude products.
In above-mentioned crude product, add 900 milliliters of dehydrated alcohols, heating for dissolving.Add again 2.0 grams of gacs, 70 DEG C of stir abouts 0.5 hour, filtered while hot, filtrate heated and stirred, 80 DEG C progressively add 900 ml deionized water, crystallisation by cooling, suction filtration, 50% washing with alcohol, vacuum-drying, obtains 86.5 grams of productive rates of Celecoxib finished product: 61%.Purity 99.73%, impurity A 0.12%, impurity B: 0.085%.Mass spectrum is consistent with example 1 with nucleus magnetic hydrogen spectrum data.
Above-described embodiment is only explanation technical conceive of the present invention and feature, and its object is to allow person skilled in the art can understand content of the present invention and implement according to this, can not limit the scope of the invention with this.All equivalences that spirit is done according to the present invention change or modify, within all should being encompassed in protection scope of the present invention.
Claims (3)
1. a synthetic method for Celecoxib, is characterized in that: described synthetic method comprises the following steps:
The first step, to adding in reaction vessel as the sodium methylate of aldol condensation catalyst with as the toluene of reaction solvent, add again raw material p-methyl aceto phenone and Trifluoroacetic Acid Ethyl Ester, stir, after fully reacting, in reaction system, add dilute hydrochloric acid with termination reaction again, after point water-yielding stratum, obtain the toluene solution of intermediate diketone;
Wherein, the mol ratio of described p-methyl aceto phenone, Trifluoroacetic Acid Ethyl Ester and sodium methylate is 1:1 ~ 1.3:1.1 ~ 1.5, and the volume ratio of p-methyl aceto phenone and toluene is 1:3 ~ 10;
Second step adds water, phase-transfer catalyst and 4-amine sulfo group hydrazinobenzene hydrochloride salt to carry out dehydration condensation reaction in the toluene solution of described intermediate diketone, makes Celecoxib reaction solution;
Wherein, described phase-transfer catalyst is selected from any one in tetrabutylammonium chloride, Tetrabutyl amonium bromide, benzyltriethylammoinium chloride and Dodecyl trimethyl ammonium chloride; The volume that adds described water is 0.5 ~ 1 times of toluene solution volume of described intermediate diketone; The mol ratio of described p-methyl aceto phenone and described phase-transfer catalyst is 1:0.005 ~ 0.05; The mol ratio of described 4-amine sulfo group hydrazinobenzene hydrochloride salt and intermediate diketone is 0.9 ~ 1.2: 1;
The 3rd step, adds toluene in the Celecoxib reaction solution making to described second step, under 20 DEG C ~ 70 DEG C conditions, and point water-yielding stratum after leaving standstill and retain organic layer, wherein, the amount of adding toluene is 2 ~ 4 times of volume of toluene in the described the first step;
Described organic layer is cooled to 0 DEG C ~ 30 DEG C again, after insulation crystallization, obtains crystallization product, then carry out successively suction filtration, toluene wash, washing, obtains Celecoxib crude product;
By the vacuum-drying 3 ~ 8 hours at 30 DEG C ~ 70 DEG C of described Celecoxib crude product, and then with the aqueous ethanolic solution that volumetric concentration is 40 ~ 60% recrystallization that decolours, obtain Celecoxib bulk drug.
2. the synthetic method of Celecoxib according to claim 1, is characterized in that: the temperature of reaction of described dehydration condensation reaction is 30 DEG C ~ 90 DEG C, keeps reaction 5 ~ 24 hours.
3. the synthetic method of Celecoxib according to claim 1, is characterized in that: in described the 3rd step, in the aqueous ethanolic solution that is 40 ~ 60%, add gac with the recrystallization that decolours to described volumetric concentration.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410183964.4A CN103923011A (en) | 2014-05-04 | 2014-05-04 | Synthetic method of celecoxib |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410183964.4A CN103923011A (en) | 2014-05-04 | 2014-05-04 | Synthetic method of celecoxib |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103923011A true CN103923011A (en) | 2014-07-16 |
Family
ID=51141434
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410183964.4A Pending CN103923011A (en) | 2014-05-04 | 2014-05-04 | Synthetic method of celecoxib |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103923011A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104177294A (en) * | 2014-08-27 | 2014-12-03 | 齐鲁天和惠世制药有限公司 | Preparation method of celecoxib |
| CN110407683A (en) * | 2019-04-03 | 2019-11-05 | 湖南方盛制药股份有限公司 | A kind of preparation method of celecoxib diketone intermediate |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1671669A (en) * | 2002-05-24 | 2005-09-21 | 法玛西雅公司 | Synthesis of diaryl pyrazoles |
| US20080234491A1 (en) * | 2007-03-19 | 2008-09-25 | Raghupathi Reddy Anumula | Process for preparation of celecoxib |
| WO2010095024A2 (en) * | 2009-02-20 | 2010-08-26 | Aurobindo Pharma Limited | An improved process for the preparation of celecoxib |
| CN102391184A (en) * | 2011-10-17 | 2012-03-28 | 江西同和药业有限责任公司 | Synthesis method of celecoxib |
| CN102746231A (en) * | 2011-04-20 | 2012-10-24 | 天津药物研究院 | Celecoxib preparation process |
| CN103044329A (en) * | 2013-01-10 | 2013-04-17 | 齐河诚汇精细化工有限公司 | Preparation method of high-yield and high-purity celecoxib |
| CN103242233A (en) * | 2012-02-08 | 2013-08-14 | 黄华 | Novel method for preparing celecoxib |
| CN103524416A (en) * | 2013-10-29 | 2014-01-22 | 中美华世通生物医药科技（武汉）有限公司 | Novel crystal form A of celecoxib and preparation method thereof |
-
2014
- 2014-05-04 CN CN201410183964.4A patent/CN103923011A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1671669A (en) * | 2002-05-24 | 2005-09-21 | 法玛西雅公司 | Synthesis of diaryl pyrazoles |
| US20080234491A1 (en) * | 2007-03-19 | 2008-09-25 | Raghupathi Reddy Anumula | Process for preparation of celecoxib |
| WO2010095024A2 (en) * | 2009-02-20 | 2010-08-26 | Aurobindo Pharma Limited | An improved process for the preparation of celecoxib |
| CN102746231A (en) * | 2011-04-20 | 2012-10-24 | 天津药物研究院 | Celecoxib preparation process |
| CN102391184A (en) * | 2011-10-17 | 2012-03-28 | 江西同和药业有限责任公司 | Synthesis method of celecoxib |
| CN103242233A (en) * | 2012-02-08 | 2013-08-14 | 黄华 | Novel method for preparing celecoxib |
| CN103044329A (en) * | 2013-01-10 | 2013-04-17 | 齐河诚汇精细化工有限公司 | Preparation method of high-yield and high-purity celecoxib |
| CN103524416A (en) * | 2013-10-29 | 2014-01-22 | 中美华世通生物医药科技（武汉）有限公司 | Novel crystal form A of celecoxib and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 梅之南，等: "COX-2抑制剂Celecoxib的合成", 《中国医药工业杂志》, vol. 31, no. 10, 31 October 2000 (2000-10-31), pages 433 - 434 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104177294A (en) * | 2014-08-27 | 2014-12-03 | 齐鲁天和惠世制药有限公司 | Preparation method of celecoxib |
| CN110407683A (en) * | 2019-04-03 | 2019-11-05 | 湖南方盛制药股份有限公司 | A kind of preparation method of celecoxib diketone intermediate |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103626774B (en) | Yi Lu is for the preparation method of Buddhist nun | |
| CN103896855B (en) | The synthetic method of the fluoro-6-chlorine of a kind of 4-(1-bromoethyl)-5-pyrimidine | |
| CN105254567A (en) | Method for preparing dexmedetomidine hydrochloride key intermediate | |
| CN103965125A (en) | Synthetic method of 3,3'-binitro-5,5'-di-1,2,4-triazole | |
| CN103923011A (en) | Synthetic method of celecoxib | |
| CN103896858B (en) | The preparation technology of cytosine | |
| CN107056756A (en) | A kind of method for preparing high-purity Losartan | |
| CN105440012A (en) | Lenalidomide and lenalidomide intermediate preparation method | |
| CN103483255B (en) | Fluorinated isoquinoline compounds and preparation method thereof | |
| CN103980134B (en) | A kind of preparation method of succsinic acid S-metoprolol | |
| CN105315258A (en) | Vonoprazan fumarate polycrystalline forms and preparation method thereof | |
| CN104177294A (en) | Preparation method of celecoxib | |
| CN102757390B (en) | Method for preparing 2-methoxy-4-diazanyl-5-fluoropyrimidine | |
| CN104292232A (en) | Synthesis method for intermediate of impurity A of pemetrexed disodium | |
| CN104326927B (en) | A kind of preparation method of 1-[2-amino-1-(4-methoxyphenyl) ethyl] Hexalin sulfate | |
| CN105272921A (en) | Method for preparing Ceritinib and intermediate compound of Ceritinib | |
| CN103570781B (en) | A kind of industrialized process for preparing of capecitabine | |
| KR20180105450A (en) | A Method of preparing Fimarsartan choline salt and hydrate thereof | |
| CN105061327A (en) | Synthetic method of long-acting sulfonamide | |
| CN102086147B (en) | Preparation method of substituted phenol | |
| CN106316950A (en) | Gliquidone preparation method | |
| CN104926807A (en) | Rivaroxaban related substance 'diamine' and synthesis method thereof | |
| CN104817548A (en) | Small organic molecule capable of realizing visual and selective recognition of lithium hydroxide, sodium hydroxide and potassium hydroxide | |
| CN103896859A (en) | Process for synthesizing cytosine | |
| CN103833530A (en) | Preparation method of organic intermediate 3-phenoxyl-1, 2-propylene glycol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C12 | Rejection of a patent application after its publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20140716 |