CN101812049A - 一种扎托布洛芬的新的制备方法 - Google Patents
一种扎托布洛芬的新的制备方法 Download PDFInfo
- Publication number
- CN101812049A CN101812049A CN200910067886A CN200910067886A CN101812049A CN 101812049 A CN101812049 A CN 101812049A CN 200910067886 A CN200910067886 A CN 200910067886A CN 200910067886 A CN200910067886 A CN 200910067886A CN 101812049 A CN101812049 A CN 101812049A
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- Prior art keywords
- zaltoprofen
- solvent
- hours
- reaction
- drying
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- 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.)
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- MUXFZBHBYYYLTH-UHFFFAOYSA-N Zaltoprofen Chemical compound O=C1CC2=CC(C(C(O)=O)C)=CC=C2SC2=CC=CC=C21 MUXFZBHBYYYLTH-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 229950004227 zaltoprofen Drugs 0.000 title claims abstract description 30
- 238000000034 method Methods 0.000 title claims abstract description 10
- 238000006243 chemical reaction Methods 0.000 claims description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 20
- 239000002994 raw material Substances 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 238000005406 washing Methods 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 150000001875 compounds Chemical class 0.000 claims description 8
- 239000012043 crude product Substances 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 8
- 230000008025 crystallization Effects 0.000 claims description 8
- 238000003810 ethyl acetate extraction Methods 0.000 claims description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 8
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims description 4
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 claims description 4
- 230000006837 decompression Effects 0.000 claims description 4
- 238000000605 extraction Methods 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 230000008014 freezing Effects 0.000 claims description 4
- 238000007710 freezing Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 4
- 238000011084 recovery Methods 0.000 claims description 4
- 238000010992 reflux Methods 0.000 claims description 4
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 4
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 4
- 238000003756 stirring Methods 0.000 claims description 4
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000012670 alkaline solution Substances 0.000 claims description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 1
- DPDMMXDBJGCCQC-UHFFFAOYSA-N [Na].[Cl] Chemical compound [Na].[Cl] DPDMMXDBJGCCQC-UHFFFAOYSA-N 0.000 claims 1
- 239000003513 alkali Substances 0.000 claims 1
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 5
- 230000036407 pain Effects 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 206010061218 Inflammation Diseases 0.000 abstract 1
- 230000000694 effects Effects 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 abstract 1
- 150000003431 steroids Chemical class 0.000 abstract 1
- 230000007062 hydrolysis Effects 0.000 description 11
- 238000006460 hydrolysis reaction Methods 0.000 description 11
- 238000007363 ring formation reaction Methods 0.000 description 9
- 230000008707 rearrangement Effects 0.000 description 8
- NRXDHTYIDMALNV-UHFFFAOYSA-N C(C)(=O)OC.ClC1=CC=CC=C1 Chemical class C(C)(=O)OC.ClC1=CC=CC=C1 NRXDHTYIDMALNV-UHFFFAOYSA-N 0.000 description 6
- 241000534944 Thia Species 0.000 description 5
- 230000032050 esterification Effects 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- 238000005907 ketalization reaction Methods 0.000 description 5
- 150000003180 prostaglandins Chemical class 0.000 description 5
- 230000000202 analgesic effect Effects 0.000 description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 3
- ZDOYHCIRUPHUHN-UHFFFAOYSA-N 1-(2-chlorophenyl)ethanone Chemical compound CC(=O)C1=CC=CC=C1Cl ZDOYHCIRUPHUHN-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 238000007171 acid catalysis Methods 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 229960000905 indomethacin Drugs 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 201000003068 rheumatic fever Diseases 0.000 description 2
- 239000012266 salt solution Substances 0.000 description 2
- 230000006103 sulfonylation Effects 0.000 description 2
- 238000005694 sulfonylation reaction Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 235000017060 Arachis glabrata Nutrition 0.000 description 1
- 241001553178 Arachis glabrata Species 0.000 description 1
- 235000010777 Arachis hypogaea Nutrition 0.000 description 1
- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 208000009386 Experimental Arthritis Diseases 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- 206010034464 Periarthritis Diseases 0.000 description 1
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 description 1
- 229960001193 diclofenac sodium Drugs 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- 229960002373 loxoprofen Drugs 0.000 description 1
- WORCCYVLMMTGFR-UHFFFAOYSA-M loxoprofen sodium Chemical compound [Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 WORCCYVLMMTGFR-UHFFFAOYSA-M 0.000 description 1
- 230000002132 lysosomal effect Effects 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 description 1
- 230000000936 membranestabilizing effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (6)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
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CN200910067886A CN101812049A (zh) | 2009-02-19 | 2009-02-19 | 一种扎托布洛芬的新的制备方法 |
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CN200910067886A CN101812049A (zh) | 2009-02-19 | 2009-02-19 | 一种扎托布洛芬的新的制备方法 |
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CN101812049A true CN101812049A (zh) | 2010-08-25 |
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CN200910067886A Pending CN101812049A (zh) | 2009-02-19 | 2009-02-19 | 一种扎托布洛芬的新的制备方法 |
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102206150A (zh) * | 2011-04-11 | 2011-10-05 | 启东东岳药业有限公司 | 2-苯基丙酸的纯化方法 |
CN104016949A (zh) * | 2014-06-25 | 2014-09-03 | 天津市炜杰科技有限公司 | 4-氨基-5-氯-2,3-二氢苯并呋喃-7-羧酸的合成方法 |
CN104098540A (zh) * | 2014-06-24 | 2014-10-15 | 浙江亚太药业股份有限公司 | 一种制备扎托布洛芬的方法 |
CN105198858A (zh) * | 2015-10-30 | 2015-12-30 | 天津药物研究院药业有限责任公司 | 扎托布洛芬的纯化方法 |
CN105218514A (zh) * | 2015-10-30 | 2016-01-06 | 天津药物研究院药业有限责任公司 | 扎托布洛芬的制备方法 |
CN110407804A (zh) * | 2019-07-18 | 2019-11-05 | 河南后羿制药有限公司 | 微通道反应器在扎托布洛芬的环合反应中的应用及扎托布洛芬的环合方法 |
CN110590737A (zh) * | 2019-09-25 | 2019-12-20 | 华中农业大学 | 一种高比活度氚标记扎托布洛芬及其制备方法 |
-
2009
- 2009-02-19 CN CN200910067886A patent/CN101812049A/zh active Pending
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102206150A (zh) * | 2011-04-11 | 2011-10-05 | 启东东岳药业有限公司 | 2-苯基丙酸的纯化方法 |
CN104098540A (zh) * | 2014-06-24 | 2014-10-15 | 浙江亚太药业股份有限公司 | 一种制备扎托布洛芬的方法 |
CN104098540B (zh) * | 2014-06-24 | 2016-02-17 | 浙江亚太药业股份有限公司 | 一种制备扎托布洛芬的方法 |
CN104016949A (zh) * | 2014-06-25 | 2014-09-03 | 天津市炜杰科技有限公司 | 4-氨基-5-氯-2,3-二氢苯并呋喃-7-羧酸的合成方法 |
CN105198858A (zh) * | 2015-10-30 | 2015-12-30 | 天津药物研究院药业有限责任公司 | 扎托布洛芬的纯化方法 |
CN105218514A (zh) * | 2015-10-30 | 2016-01-06 | 天津药物研究院药业有限责任公司 | 扎托布洛芬的制备方法 |
CN110407804A (zh) * | 2019-07-18 | 2019-11-05 | 河南后羿制药有限公司 | 微通道反应器在扎托布洛芬的环合反应中的应用及扎托布洛芬的环合方法 |
CN110590737A (zh) * | 2019-09-25 | 2019-12-20 | 华中农业大学 | 一种高比活度氚标记扎托布洛芬及其制备方法 |
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Owner name: TIANJIN HANKANG PHARMACEUTICAL BIOTECHNOLOGY CO., Free format text: FORMER OWNER: YAN JIE Effective date: 20120210 |
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Effective date of registration: 20120210 Address after: 300203, Tianjin Dagu South Road, respect 4, 3, Hexi District Applicant after: Tianjin Hankang Pharmaceutical Biotechnology Co., Ltd. Address before: 300203, Tianjin Dagu South Road, respect 4, 3, Hexi District Applicant before: Yan Jie |
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Application publication date: 20100825 |