CN107778204B - 一种非罗考昔中间体的制备方法 - Google Patents
一种非罗考昔中间体的制备方法 Download PDFInfo
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- CN107778204B CN107778204B CN201711015348.8A CN201711015348A CN107778204B CN 107778204 B CN107778204 B CN 107778204B CN 201711015348 A CN201711015348 A CN 201711015348A CN 107778204 B CN107778204 B CN 107778204B
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- reaction
- aromatic hydrocarbon
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- halogenated aromatic
- hydrocarbon containing
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- 238000002360 preparation method Methods 0.000 title abstract description 7
- 238000006243 chemical reaction Methods 0.000 claims abstract description 43
- -1 isobutyryl Chemical group 0.000 claims abstract description 26
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims abstract description 23
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000003446 ligand Substances 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 239000001301 oxygen Substances 0.000 claims abstract description 11
- 239000003513 alkali Substances 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 17
- YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 claims description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- IGRZHPVXPZFKGB-UHFFFAOYSA-N 1-(4-iodophenyl)-2-methylpropan-1-one Chemical compound CC(C)C(=O)C1=CC=C(I)C=C1 IGRZHPVXPZFKGB-UHFFFAOYSA-N 0.000 claims description 8
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 claims description 8
- 229940112669 cuprous oxide Drugs 0.000 claims description 8
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical group [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 claims description 8
- 239000008367 deionised water Substances 0.000 claims description 8
- 229910021641 deionized water Inorganic materials 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 8
- 238000001704 evaporation Methods 0.000 claims description 8
- 230000008020 evaporation Effects 0.000 claims description 8
- 238000000605 extraction Methods 0.000 claims description 8
- 238000002156 mixing Methods 0.000 claims description 8
- 239000012074 organic phase Substances 0.000 claims description 8
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 8
- 238000010992 reflux Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 238000003756 stirring Methods 0.000 claims description 8
- FDCUGWDQOGIBGG-UHFFFAOYSA-N 2-methyl-1-(4-methylsulfonylphenyl)propan-1-one Chemical compound CC(C)C(=O)C1=CC=C(S(C)(=O)=O)C=C1 FDCUGWDQOGIBGG-UHFFFAOYSA-N 0.000 claims description 7
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 7
- 239000012045 crude solution Substances 0.000 claims description 4
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 239000002994 raw material Substances 0.000 abstract description 11
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 abstract description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 4
- 230000006378 damage Effects 0.000 abstract description 3
- 238000007086 side reaction Methods 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 150000003568 thioethers Chemical class 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 150000003462 sulfoxides Chemical class 0.000 abstract 1
- 238000013375 chromatographic separation Methods 0.000 description 6
- 150000001879 copper Chemical class 0.000 description 6
- 150000002940 palladium Chemical class 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 4
- 230000035484 reaction time Effects 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- 208000012839 conversion disease Diseases 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 2
- 102000010907 Cyclooxygenase 2 Human genes 0.000 description 2
- 108010037462 Cyclooxygenase 2 Proteins 0.000 description 2
- 208000002193 Pain Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 2
- 229960004643 cupric oxide Drugs 0.000 description 2
- 229940045803 cuprous chloride Drugs 0.000 description 2
- 231100000086 high toxicity Toxicity 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 2
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 2
- ROFVEXUMMXZLPA-UHFFFAOYSA-N Bipyridyl Chemical compound N1=CC=CC=C1C1=CC=CC=N1 ROFVEXUMMXZLPA-UHFFFAOYSA-N 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 238000005727 Friedel-Crafts reaction Methods 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C315/00—Preparation of sulfones; Preparation of sulfoxides
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
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CN201711015348.8A CN107778204B (zh) | 2017-10-26 | 2017-10-26 | 一种非罗考昔中间体的制备方法 |
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CN107778204A CN107778204A (zh) | 2018-03-09 |
CN107778204B true CN107778204B (zh) | 2020-04-03 |
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Families Citing this family (3)
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CN107686471B (zh) * | 2017-09-28 | 2020-07-03 | 成都苑东生物制药股份有限公司 | 一种非罗考昔及其中间体的合成方法 |
CN112500321A (zh) * | 2020-09-25 | 2021-03-16 | 安徽省公众检验研究院有限公司 | 一种非罗考昔关键中间体的制备方法 |
CN112624943B (zh) * | 2020-12-28 | 2022-07-01 | 成都伊诺达博医药科技有限公司 | 一种非罗考昔中间体的合成方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1552707A (zh) * | 2003-06-03 | 2004-12-08 | 李小虎 | 4-芳基-5h-噻吩-2-酮衍生物、其制法和用途 |
CN105859664A (zh) * | 2016-05-03 | 2016-08-17 | 中国药科大学 | 非罗考昔的一种制备方法 |
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- 2017-10-26 CN CN201711015348.8A patent/CN107778204B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1552707A (zh) * | 2003-06-03 | 2004-12-08 | 李小虎 | 4-芳基-5h-噻吩-2-酮衍生物、其制法和用途 |
CN105859664A (zh) * | 2016-05-03 | 2016-08-17 | 中国药科大学 | 非罗考昔的一种制备方法 |
Non-Patent Citations (1)
Title |
---|
Copper-catalyzed aerobic oxidation and cleavage/formation of C–S bond:a novel synthesis of aryl methyl sulfones from aryl halides and DMSO;Gaoqing Yuan等;《Chem. Commun.》;20121231;第48卷(第60期);表格2 * |
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Address after: 225200 No.86 Shuangshu Road, Xiannv Town, Jiangdu District, Yangzhou City, Jiangsu Province Patentee after: Tianhe Pharmaceutical Co.,Ltd. Address before: No. 86, Shuangshu Road, Xiannv Town, Jiangdu District, Yangzhou City, Jiangsu Province, 225000 Patentee before: YANGZHOU TIANHE PHARMACEUTICAL Co.,Ltd. |
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CP01 | Change in the name or title of a patent holder |
Address after: 225200 No.86 Shuangshu Road, Xiannv Town, Jiangdu District, Yangzhou City, Jiangsu Province Patentee after: Tianhe Pharmaceutical Co.,Ltd. Address before: 225200 No.86 Shuangshu Road, Xiannv Town, Jiangdu District, Yangzhou City, Jiangsu Province Patentee before: YANGZHOU TIANHE PHARMACEUTICAL Co.,Ltd. |
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Denomination of invention: A preparation method of ferrocoxib intermediate Effective date of registration: 20220129 Granted publication date: 20200403 Pledgee: Yangzhou Branch of Bank of Jiangsu Co.,Ltd. Pledgor: Tianhe Pharmaceutical Co.,Ltd. Registration number: Y2022980001363 |
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Date of cancellation: 20230328 Granted publication date: 20200403 Pledgee: Yangzhou Branch of Bank of Jiangsu Co.,Ltd. Pledgor: Tianhe Pharmaceutical Co.,Ltd. Registration number: Y2022980001363 |
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Address after: 225200 No.86 Shuangshu Road, Xiannv Town, Jiangdu District, Yangzhou City, Jiangsu Province Patentee after: Tianhe Pharmaceutical Co.,Ltd. Country or region after: China Address before: 225200 No.86 Shuangshu Road, Xiannv Town, Jiangdu District, Yangzhou City, Jiangsu Province Patentee before: Tianhe Pharmaceutical Co.,Ltd. Country or region before: China |