CN104557754A - Synthesis method for parecoxib sodium impurity - Google Patents
Synthesis method for parecoxib sodium impurity Download PDFInfo
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- CN104557754A CN104557754A CN201510002040.4A CN201510002040A CN104557754A CN 104557754 A CN104557754 A CN 104557754A CN 201510002040 A CN201510002040 A CN 201510002040A CN 104557754 A CN104557754 A CN 104557754A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more 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
Abstract
The invention disclose a synthesis method for a parecoxib sodium impurity namely N-[[4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl]sulfonyl] acetamide and belongs to the technical field of chemical pharmacy. According to the synthesis method, 5-methyl-3,4-diphenyl isoxazole is used as raw material, sulfonation reaction, aminating reaction and propionylation reaction are performed so as to obtain the parecoxib sodium impurity, and the synthesized high-purity parecoxib sodium impurity can be used as a standard impurity for detection analysis of a parecoxib sodium finished product, so that accurate positioning and quantification of the parecoxib sodium finished product detection analysis to the impurity are improved, control over the impurity is strengthened, and the quality of the parecoxib sodium finished product is improved. The method provided by the invention has the advantages that the raw material is cheap and easy to obtain, the operation is simple, the product yield is 65%+/-5%, and the HPLC purity is larger than or equal to 98%.
Description
Technical field
The invention belongs to technical field of pharmaceutical chemistry, be specifically related to the synthetic method of a kind of Parecoxib sodium impurity K (N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] ethanamide).
Background technology
After the noxious stimulations such as operation, wound, Inflammatory response can cause the release of inflammatory mediator and algogenic substance, they are except direct induced pain, also can distend the blood vessels, tissue edema, make that effector ceptor susceptibility increases, the threshold of pain reduces, thus cause peripheral pain perception irritated.Selective COX-2 inhibitor can effectively suppress periphery COX-2 to express, reduce periphery prostaglandin(PG) synthesis, thus play analgesic and anti-inflammatory effects, maincenter COX-2 can be suppressed to express simultaneously, suppression maincenter prostaglandin(PG) synthesizes and inhibition of pain is super quick, plays periphery, the dual analgesia advantage of maincenter.
Parecoxib Sodium chemistry is by name: N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] propionamide sodium salt; Parecoxib Sodium is a kind of highly selective inhibition of COX-2; can be used for the short of postoperative pain, there is desirable water-soluble physico-chemical property.
Impurity K chemical name: N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] ethanamide; No. CAS: 198471-06-6; produce for diacetyl oxide a small amount of in propionic anhydride in Parecoxib Sodium building-up process and intermediate react; may remain in Parecoxib Sodium finished product; affect quality product, its structural formula is as shown in (I).Through retrieval, not yet there is the bibliographical information synthesized about this impurity, therefore, provide the synthetic method of a kind of Parecoxib sodium impurity K to have important practical significance for the preparation of contamination levels product.
Summary of the invention
The object of the invention is to the shortcoming overcoming prior art; a kind of Parecoxib sodium impurity K synthetic method of (N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] ethanamide) is provided; this synthetic method has simple to operate, raw material and is cheaply easy to get, the advantage that yield is high, purity is high.
Object of the present invention is achieved through the following technical solutions: the synthetic method of a kind of Parecoxib sodium impurity K, and described impurity K is N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] ethanamide, and synthetic route is as follows:
Concrete preparation method comprises the following steps:
S1. sulfonation reaction: add methylene dichloride and 5-methyl-3,4-phenylbenzene isoxzzole in reactor, controls temperature of reaction lower than 30 DEG C, drip chlorsulfonic acid, dropwise and be warming up to 40 ~ 50 DEG C, backflow 3 ~ 8h to 5-methyl-3,4-phenylbenzene isoxzzole reacts completely, and generates intermediate compound I;
S2. amination reaction: add frozen water by the reaction solution after sulfonation reaction, uses dichloromethane extraction separatory, adds ammoniacal liquor in organic phase, and control temperature is 20 ~ 30 DEG C, and reaction 1 ~ 3h, generates intermediate II;
S3. acetylization reaction: add intermediate II, triethylamine, DMAP, methylene dichloride in reaction flask, agitation and dropping diacetyl oxide at 15 ~ 30 DEG C of temperature, reaction 1 ~ 4h generates Parecoxib sodium impurity K.
Further, the weight ratio of described 5-methyl-3,4-phenylbenzene isoxzzole, chlorsulfonic acid and ammoniacal liquor is 1:3 ~ 5:3 ~ 5.
Further, the weight ratio of intermediate II described in step S3, triethylamine, DMAP, diacetyl oxide is 1:0.2 ~ 0.5:0.01 ~ 0.03:0.1 ~ 0.5.
Further, step S3 also comprises the step of aftertreatment, described post-treating method is: after reacting completely, concentrating under reduced pressure under pressure≤-0.07MPa, temperature are the condition of 35 ~ 45 DEG C, residue adds ethyl acetate washing, again add ethyl acetate after concentrating under reduced pressure, normal hexane carries out crystallization 1 ~ 4h, gained crystal is dry 5 ~ 10h at 50 ~ 80 DEG C of temperature, obtains Parecoxib sodium impurity K.
The present invention has the following advantages: the present invention is with 5-methyl-3, 4-phenylbenzene isoxzzole is raw material, through sulfonation reaction, amination reaction and acetylization reaction obtain Parecoxib sodium impurity K, the Parecoxib sodium impurity K of synthesis of high purity can be used as the impurity K standard substance in the analysis of Parecoxib Sodium finished product detection, thus promote Parecoxib Sodium finished product detection and analyze the accurate polarization of impurity K and qualitative, be conducive to strengthening the control to this impurity, and then improve Parecoxib Sodium final product quality, method raw material provided by the invention is cheaply easy to get, simple to operate, products obtained therefrom yield 65% ± 5%, HPLC purity >=98%.
Accompanying drawing explanation
Fig. 1 is Parecoxib sodium impurity K HPLC collection of illustrative plates;
Fig. 2 is Parecoxib sodium impurity K mass spectrum;
Fig. 3 is Parecoxib sodium impurity K hydrogen nuclear magnetic resonance spectrogram.
Embodiment
Below in conjunction with drawings and Examples, the present invention will be further described, and protection scope of the present invention is not limited to the following stated.
Embodiment 1: the synthetic method of a kind of Parecoxib sodium impurity K (N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] ethanamide)
20g methylene dichloride and 5g5-methyl-3 is added in reaction flask, 4-phenylbenzene isoxzzole, control temperature of reaction lower than 30 DEG C, drip 15g chlorsulfonic acid, dropwise and be warming up to 40 ~ 50 DEG C, backflow 3h, sampling TLC (EA:PE=1:3) monitoring in every 0.5 hour once, is reacted to the disappearance of TLC monitoring 5-methyl-3,4-phenylbenzene isoxzzole spot, namely 5-methyl-3,4-phenylbenzene isoxzzole reacts completely;
Reaction solution is cooled to room temperature, drop in 20g frozen water, temperature control is lower than 20 DEG C, and dropwise rear 15g dichloromethane extraction separatory, aqueous phase adds 10g dichloromethane extraction again, merge organic phase (dichloromethane solution of intermediate compound I), agitation and dropping is in 15g ammoniacal liquor, and control temperature is 20 ~ 30 DEG C, is added dropwise to complete rear insulation 1h, monitor once with TLC (EA:PE=1:3) sampling in every 0.5 hour, react to the disappearance of TLC monitoring intermediate compound I spot.After completion of the reaction, extremely do not become line to drip at 45 DEG C of concentrating under reduced pressure (≤-0.07MPa) reaction solutions reaction solution, filter, wash filter cake with water 3 times, use water 10g at every turn, by filter cake in 70 DEG C of hot-air ovens dryings 20 hours, obtain intermediate II 6.13g, yield is 91.7%;
5g intermediate II is added in reaction flask, 1g triethylamine, 0.05gDMAP, 20g methylene dichloride, agitation and dropping 0.5g diacetyl oxide at 15 DEG C of temperature, reaction 4h, react complete, 35 DEG C of concentrating under reduced pressure (≤-0.07MPa), add 20g ethyl acetate in residue, wash three times, each 10g, 50 DEG C of pressurizations are concentrated, concentrated complete, add 5g ethyl acetate, 6g normal hexane crystallization 1h, filter, gained crystal dry 5h at 50 DEG C of temperature obtains 3.85g white solid, be Parecoxib sodium impurity K, yield 67.9%.
As shown in Figure 1, purity is 98.5% to Parecoxib sodium impurity K HPLC collection of illustrative plates.
Parecoxib sodium impurity K mass spectrum as shown in Figure 2, MS:379 (M+Na
+);
As shown in Figure 3, H spectrum display chemical shift δ (7.240-8.017), 9 hydrogen are benzene ring hydrogen to Parecoxib sodium impurity K proton nmr spectra.Chemical shift δ (2.457-2.450) totally 3 hydrogen is the CH on aromatic ring
3hydrogen.Chemical shift δ (2.081) totally 3 hydrogen is straight chain C H
3hydrogen, detected result conforms to Parecoxib sodium impurity K structure.
Embodiment 2: the synthetic method of a kind of Parecoxib sodium impurity K (N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] ethanamide)
20g methylene dichloride and 5g 5-methyl-3 is added in reaction flask, 4-phenylbenzene isoxzzole, control temperature of reaction lower than 30 DEG C, drip 20g chlorsulfonic acid, dropwise and be warming up to 40 ~ 50 DEG C, backflow 8h, sampling TLC (EA:PE=1:3) monitoring in every 0.5 hour once, is reacted to the disappearance of TLC monitoring 5-methyl-3,4-phenylbenzene isoxzzole spot, namely 5-methyl-3,4-phenylbenzene isoxzzole reacts completely;
Reaction solution is cooled to room temperature, drop in 20g frozen water, temperature control is lower than 20 DEG C, and dropwise rear 15g dichloromethane extraction separatory, aqueous phase adds 10g dichloromethane extraction again, merge organic phase (dichloromethane solution of intermediate compound I), agitation and dropping is to 20g ammoniacal liquor, and control temperature is 20 ~ 30 DEG C, is added dropwise to complete rear insulation 3h, monitor once with TLC (EA:PE=1:3) sampling in every 0.5 hour, react to the disappearance of TLC monitoring intermediate compound I spot.After completion of the reaction, extremely do not become line to drip at 45 DEG C of concentrating under reduced pressure (≤-0.07MPa) reaction solutions reaction solution, filter, wash filter cake with water 3 times, use water 10g at every turn, by filter cake in 70 DEG C of hot-air ovens dryings 20 hours, obtain intermediate II 6.05g, yield is 90.5%;
5g intermediate II is added in reaction flask, 1.5g triethylamine, 0.08g DMAP, 20g methylene dichloride, agitation and dropping 1.5g propionic anhydride at 20 DEG C of temperature, reaction 2h, reacts complete, 45 DEG C of concentrating under reduced pressure (≤-0.07MPa), 15g ethyl acetate is added in residue, wash three times, each 10g, 50 DEG C of concentrating under reduced pressure, concentrated complete, add 5g ethyl acetate, 6g normal hexane crystallization 3h, filter, gained crystal dry 8h at 70 DEG C of temperature obtains 3.94g white solid, be Parecoxib sodium impurity K, yield 69.5%, purity >=98.4%.
Embodiment 3: the synthetic method of a kind of Parecoxib sodium impurity K (N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] ethanamide)
20g methylene dichloride and 5g 5-methyl-3 is added in reaction flask, 4-phenylbenzene isoxzzole, control temperature of reaction lower than 30 DEG C, drip 25g chlorsulfonic acid, dropwise and be warming up to 40 ~ 50 DEG C, backflow 6h, sampling TLC (EA:PE=1:3) monitoring in every 0.5 hour once, is reacted to the disappearance of TLC monitoring 5-methyl-3,4-phenylbenzene isoxzzole spot, namely 5-methyl-3,4-phenylbenzene isoxzzole reacts completely;
Reaction solution is cooled to room temperature, drop in 20g frozen water, temperature control is lower than 20 DEG C, and dropwise rear 15g dichloromethane extraction separatory, aqueous phase adds 10g dichloromethane extraction again, merge organic phase (dichloromethane solution of intermediate compound I), agitation and dropping is to 20g18g ammoniacal liquor, and control temperature is 20 ~ 30 DEG C, is added dropwise to complete rear insulation 1.5h, monitor once with TLC (EA:PE=1:3) sampling in every 0.5 hour, react to the disappearance of TLC monitoring intermediate compound I spot.After completion of the reaction, extremely do not become line to drip at 45 DEG C of concentrating under reduced pressure (≤-0.07MPa) reaction solutions reaction solution, filter, wash filter cake with water 3 times, use water 10g at every turn, by filter cake in 70 DEG C of hot-air ovens dryings 20 hours, obtain intermediate II 6.02g, yield is 90.1%;
6g intermediate II is added in reaction flask, 2.4g triethylamine, 0.18gDMAP, 25g methylene dichloride, agitation and dropping 2.4g propionic anhydride reaction 1h at 30 DEG C of temperature, react complete, 40 DEG C of concentrating under reduced pressure (≤-0.07MPa), add 15g ethyl acetate in residue, wash three times, each 10g, 50 DEG C of concentrating under reduced pressure, concentrated complete, add 5g ethyl acetate, 6g normal hexane crystallization 2h, filter, gained crystal dry 10h at 60 DEG C of temperature obtains 4.38g white solid, is Parecoxib sodium impurity K, yield 64..4%, purity >=99.6%.
Embodiment 4: the synthetic method of a kind of Parecoxib sodium impurity K (N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] ethanamide)
20g methylene dichloride and 5g 5-methyl-3 is added in reactor, 4-phenylbenzene isoxzzole, control temperature of reaction lower than 30 DEG C, drip 18g chlorsulfonic acid, dropwise and be warming up to 40 ~ 50 DEG C, backflow 4h, sampling TLC (EA:PE=1:3) monitoring in every 0.5 hour once, is reacted to the disappearance of TLC monitoring 5-methyl-3,4-phenylbenzene isoxzzole spot, namely 5-methyl-3,4-phenylbenzene isoxzzole reacts completely;
Reaction solution is cooled to room temperature, drop in 20g frozen water, temperature control is lower than 20 DEG C, and dropwise rear 15g dichloromethane extraction separatory, aqueous phase adds 10g dichloromethane extraction again, merge organic phase (dichloromethane solution of intermediate compound I), agitation and dropping is to 20g 25g ammoniacal liquor, and control temperature is 28 DEG C, is added dropwise to complete rear insulation 2.5h, monitor once with TLC (EA:PE=1:3) sampling in every 0.5 hour, react to the disappearance of TLC monitoring intermediate compound I spot.After completion of the reaction, extremely do not become line to drip at 45 DEG C of concentrating under reduced pressure (≤-0.07MPa) reaction solutions reaction solution, filter, wash filter cake with water 3 times, use water 5Kg at every turn, by filter cake in 70 DEG C of hot-air ovens dryings 20 hours, obtain intermediate II 5.45Kg, yield is 90.6%;
6g intermediate II is added in reaction flask, 3.0g triethylamine, 0.15gDMAP, 25g methylene dichloride, agitation and dropping 3.0g propionic anhydride reaction 3h at 25 DEG C of temperature, react complete, 50 DEG C of concentrating under reduced pressure (≤-0.07MPa), add 15g ethyl acetate in residue, wash three times, each 10g, 50 DEG C of concentrating under reduced pressure, concentrated complete, add 5g ethyl acetate, 6g normal hexane crystallization 4h, filter, gained crystal dry 7h at 80 DEG C of temperature obtains 4.55g white solid, is Parecoxib sodium impurity K, yield 66.9%, purity >=99.3%.
Claims (4)
1. a synthetic method for Parecoxib sodium impurity, described impurity is N-[[4-(5-methyl-3-phenyl-4-isoxazolyl) phenyl] alkylsulfonyl] ethanamide, and it is characterized in that, synthetic route is as follows:
Concrete preparation method comprises the following steps:
S1. sulfonation reaction: add methylene dichloride and 5-methyl-3,4-phenylbenzene isoxzzole in reactor, controls temperature of reaction lower than 30 DEG C, drip chlorsulfonic acid, dropwise and be warming up to 40 ~ 50 DEG C, backflow 3 ~ 8h to 5-methyl-3,4-phenylbenzene isoxzzole reacts completely, and generates intermediate compound I;
S2. amination reaction: add frozen water by the reaction solution after sulfonation reaction, uses dichloromethane extraction separatory, adds ammoniacal liquor in organic phase, and control temperature is 20 ~ 30 DEG C, and reaction 1 ~ 3h, generates intermediate II;
S3. acetylization reaction: add intermediate II, triethylamine, DMAP, methylene dichloride in reaction flask, agitation and dropping diacetyl oxide at 15 ~ 30 DEG C of temperature, reaction 1 ~ 4h generates Parecoxib sodium impurity.
2. the synthetic method of a kind of Parecoxib sodium impurity as claimed in claim 1, is characterized in that, the weight ratio of described 5-methyl-3,4-phenylbenzene isoxzzole, chlorsulfonic acid and ammoniacal liquor is 1:3 ~ 5:3 ~ 5.
3. the synthetic method of a kind of Parecoxib sodium impurity as claimed in claim 1, is characterized in that, the weight ratio of intermediate II described in step S3, triethylamine, DMAP, diacetyl oxide is 1:0.2 ~ 0.5:0.01 ~ 0.03:0.1 ~ 0.5.
4. the synthetic method of a kind of Parecoxib sodium impurity as claimed in claim 1, it is characterized in that, step S3 also comprises the step of aftertreatment, described post-treating method is: after reacting completely, concentrating under reduced pressure under pressure≤-0.07MPa, temperature are the condition of 35 ~ 45 DEG C, residue adds ethyl acetate washing, again adds ethyl acetate after concentrating under reduced pressure, normal hexane carries out crystallization 1 ~ 4h, gained crystal is dry 5 ~ 10h at 50 ~ 80 DEG C of temperature, obtains Parecoxib sodium impurity.
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104965041A (en) * | 2015-06-11 | 2015-10-07 | 成都克莱蒙医药科技有限公司 | High performance liquid chromatography detection method for parecoxib sodium isomer |
| CN107976500A (en) * | 2017-11-29 | 2018-05-01 | 浙江震元制药有限公司 | A kind of isoxazole compound of double aryl substitutions and its preparation method and application |
| CN108675969A (en) * | 2018-05-14 | 2018-10-19 | 四川尚锐生物医药有限公司 | A kind of preparation method of SC 69124 sodium impurity |
| CN109134395A (en) * | 2018-09-25 | 2019-01-04 | 珠海赛隆药业股份有限公司 | The synthetic method of Parecoxib Sodium Isomeric impurities |
| CN109734681A (en) * | 2019-02-13 | 2019-05-10 | 四川蓝励医药科技有限公司 | SC 69124 sodium impurity and preparation method thereof |
| CN110041282A (en) * | 2018-01-15 | 2019-07-23 | 正大天晴药业集团股份有限公司 | Related substance of Parecoxib Sodium and its preparation method and application |
| CN110240570A (en) * | 2018-03-07 | 2019-09-17 | 浙江震元制药有限公司 | A kind of preparation method of SC 69124 sodium impurity |
| CN111100084A (en) * | 2019-12-30 | 2020-05-05 | 山东罗欣药业集团恒欣药业有限公司 | Preparation method of parecoxib sodium |
| CN113773270A (en) * | 2021-08-06 | 2021-12-10 | 四川新开元制药有限公司 | Synthesis method of parecoxib sodium impurity |
| CN115304555A (en) * | 2021-05-06 | 2022-11-08 | 北京新康哌森医药科技有限公司 | Synthesis method of parecoxib sodium impurity |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1216043A (en) * | 1996-04-12 | 1999-05-05 | G·D·瑟尔公司 | Substd. benzenesulfonamide derivs as prodrugs of COX-2 inhibitors |
| EP1550658A1 (en) * | 2003-12-30 | 2005-07-06 | Dr. Reddy's Laboratories Ltd. | Method for preparing 3,4-diphenyl-substituted isoxazole compounds |
| CN104250232A (en) * | 2013-06-26 | 2014-12-31 | 四川唯拓生物医药有限公司 | Preparation method of parecoxib sodium |
-
2015
- 2015-01-04 CN CN201510002040.4A patent/CN104557754A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1216043A (en) * | 1996-04-12 | 1999-05-05 | G·D·瑟尔公司 | Substd. benzenesulfonamide derivs as prodrugs of COX-2 inhibitors |
| EP1550658A1 (en) * | 2003-12-30 | 2005-07-06 | Dr. Reddy's Laboratories Ltd. | Method for preparing 3,4-diphenyl-substituted isoxazole compounds |
| CN104250232A (en) * | 2013-06-26 | 2014-12-31 | 四川唯拓生物医药有限公司 | Preparation method of parecoxib sodium |
Non-Patent Citations (2)
| Title |
|---|
| ANUMULA RAGHUPATHI REDDY ET AL.: "Application of [3+2]-Cycloaddition in the Synthesis of Valdecoxib", 《SYNTHETIC COMMUNICATIONS》, vol. 42, 24 August 2011 (2011-08-24) * |
| JOHN J. TALLEY ET AL.: "N-[[(5-Methyl-3-phenylisoxazol-4-yl)-phenyl]-sulfonyl]propanamide, Sodium Salt, Parecoxib Sodium: A Potent and Selective Inhibitor of COX-2 for Parenteral Administration", 《J. MED. CHEM.》, vol. 43, 5 April 2000 (2000-04-05), XP 002335575, DOI: doi:10.1021/jm000069h * |
Cited By (14)
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| CN104965041A (en) * | 2015-06-11 | 2015-10-07 | 成都克莱蒙医药科技有限公司 | High performance liquid chromatography detection method for parecoxib sodium isomer |
| CN104965041B (en) * | 2015-06-11 | 2016-06-29 | 成都克莱蒙医药科技有限公司 | A kind of high-efficiency liquid chromatography method for detecting of Parecoxib Sodium isomer |
| CN107976500A (en) * | 2017-11-29 | 2018-05-01 | 浙江震元制药有限公司 | A kind of isoxazole compound of double aryl substitutions and its preparation method and application |
| CN107976500B (en) * | 2017-11-29 | 2021-09-28 | 浙江震元制药有限公司 | Diaryl-substituted isoxazole compound and preparation method and application thereof |
| CN110041282A (en) * | 2018-01-15 | 2019-07-23 | 正大天晴药业集团股份有限公司 | Related substance of Parecoxib Sodium and its preparation method and application |
| CN110041282B (en) * | 2018-01-15 | 2022-05-20 | 正大天晴药业集团股份有限公司 | Parecoxib sodium related substance, preparation method and application thereof |
| CN110240570A (en) * | 2018-03-07 | 2019-09-17 | 浙江震元制药有限公司 | A kind of preparation method of SC 69124 sodium impurity |
| CN108675969A (en) * | 2018-05-14 | 2018-10-19 | 四川尚锐生物医药有限公司 | A kind of preparation method of SC 69124 sodium impurity |
| CN109134395A (en) * | 2018-09-25 | 2019-01-04 | 珠海赛隆药业股份有限公司 | The synthetic method of Parecoxib Sodium Isomeric impurities |
| CN109734681A (en) * | 2019-02-13 | 2019-05-10 | 四川蓝励医药科技有限公司 | SC 69124 sodium impurity and preparation method thereof |
| CN111100084A (en) * | 2019-12-30 | 2020-05-05 | 山东罗欣药业集团恒欣药业有限公司 | Preparation method of parecoxib sodium |
| CN111100084B (en) * | 2019-12-30 | 2022-12-06 | 山东罗欣药业集团恒欣药业有限公司 | Preparation method of parecoxib sodium |
| CN115304555A (en) * | 2021-05-06 | 2022-11-08 | 北京新康哌森医药科技有限公司 | Synthesis method of parecoxib sodium impurity |
| CN113773270A (en) * | 2021-08-06 | 2021-12-10 | 四川新开元制药有限公司 | Synthesis method of parecoxib sodium impurity |
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Application publication date: 20150429 |