PT2440543E - Método melhorado para a síntese de pirfenidona - Google Patents
Método melhorado para a síntese de pirfenidona Download PDFInfo
- Publication number
- PT2440543E PT2440543E PT107840217T PT10784021T PT2440543E PT 2440543 E PT2440543 E PT 2440543E PT 107840217 T PT107840217 T PT 107840217T PT 10784021 T PT10784021 T PT 10784021T PT 2440543 E PT2440543 E PT 2440543E
- Authority
- PT
- Portugal
- Prior art keywords
- pirfenidone
- solution
- weight
- bromobenzene
- molar ratio
- Prior art date
Links
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 title claims description 110
- 229960003073 pirfenidone Drugs 0.000 title claims description 110
- 238000000034 method Methods 0.000 title claims description 44
- 230000002194 synthesizing effect Effects 0.000 title 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 45
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 27
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 20
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 16
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
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- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pyridine Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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| US8304413B2 (en) | 2008-06-03 | 2012-11-06 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| DK2670242T3 (da) | 2011-01-31 | 2022-05-02 | Avalyn Pharma Inc | Aerosolpirfenidon- og pyridonanalogforbindelser og anvendelser deraf |
| US10105356B2 (en) | 2011-01-31 | 2018-10-23 | Avalyn Pharma Inc. | Aerosol pirfenidone and pyridone analog compounds and uses thereof |
| MX2011007675A (es) | 2011-07-19 | 2012-07-11 | Cell Therapy And Technology S A De C V | Procedimiento para la fabricacion de una composicion farmaceutica en forma de tabletas de liberacion prolongada conteniendo pirfenidona y su aplicacion en la regresion de la insuficiencia renal cronica, contractura capsular mamaria y fibrosis hepatica humanas. |
| MX356551B (es) | 2012-08-23 | 2018-06-04 | Grupo Medifarma S A De C V Star | Composición antiséptica, antiseborreica y exfoliante para eliminar o prevenir el acné. |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| AU2015204558B2 (en) | 2014-01-10 | 2020-04-30 | Avalyn Pharma Inc. | Aerosol pirfenidone and pyridone analog compounds and uses thereof |
| RU2692485C2 (ru) | 2014-04-02 | 2019-06-25 | Интермьюн, Инк. | Противофиброзные пиридиноны |
| WO2016025789A1 (en) * | 2014-08-15 | 2016-02-18 | PixarBio Corporation | Compositions for inhibting inflammation in a subject with a spinal cord injury and methods of using the same |
| WO2016122420A1 (en) | 2015-01-26 | 2016-08-04 | Ulkar Kimya Sanayii Ve Ticaret A. S. | An improved method for the synthesis and purification of pirfenidone |
| ITUB20154832A1 (it) | 2015-10-29 | 2017-04-29 | Procos Spa | Processo per la sintesi di pirfenidone |
| CN105315198A (zh) * | 2015-11-02 | 2016-02-10 | 重庆康乐制药有限公司 | 一种吡非尼酮的晶型及其制备方法 |
| CN105330598B (zh) * | 2015-12-02 | 2017-11-14 | 新发药业有限公司 | 一种吡非尼酮的制备方法 |
| WO2017122139A1 (en) * | 2016-01-14 | 2017-07-20 | Laurus Labs Limited | An improved process for the preparation of pirfenidone |
| US11066368B2 (en) | 2016-01-14 | 2021-07-20 | Laurus Labs Limited | Process for the preparation and particle size reduction of pirfenidone |
| WO2017130166A1 (en) * | 2016-01-31 | 2017-08-03 | Granules India Limited | An improved process for the preparation of highly pure anti-fibrotic drug |
| CA2937365C (en) | 2016-03-29 | 2018-09-18 | F. Hoffmann-La Roche Ag | Granulate formulation of 5-methyl-1-phenyl-2-(1h)-pyridone and method of making the same |
| IT201600071672A1 (it) * | 2016-07-08 | 2018-01-08 | Dipharma Francis Srl | Metodo per sintetizzare un farmaco immunosoppressore |
| US20180009753A1 (en) * | 2016-07-08 | 2018-01-11 | Dipharma Francis S.R.L. | Method for preparing an antifibrotic agent |
| IT201600108927A1 (it) * | 2016-10-27 | 2018-04-27 | Dipharma Francis Srl | Metodo per sintetizzare un farmaco antifibrotico |
| WO2018083709A1 (en) * | 2016-11-07 | 2018-05-11 | Msn Laboratories Private Limited, R&D Center | Improved process for the preparation of pure 5-methyl-1-phenyl-2-1 (h)-pyridone |
| WO2018178996A1 (en) * | 2017-03-28 | 2018-10-04 | Natco Pharma Limited | Improved process for the preparation of pirfenidone |
| EP3661506B1 (en) | 2017-07-31 | 2025-01-29 | Washington University | Pirfenidone derivatives for modulation of b lymphocyte activity and organ protection |
| ES2886152T3 (es) | 2017-12-11 | 2021-12-16 | Laurus Labs Ltd | Un procedimiento mejorado para la preparación de pirfenidona |
| CN112409246B (zh) * | 2019-08-21 | 2023-04-07 | 北京凯因科技股份有限公司 | 一种吡非尼酮的晶型及其制备方法 |
| KR102584268B1 (ko) * | 2020-04-22 | 2023-10-05 | 영진약품 주식회사 | 안전성과 안정성이 개선된 피르페니돈을 포함하는 장용성 제제 및 이의 제조방법 |
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| US3839346A (en) * | 1972-12-18 | 1974-10-01 | Affiliated Med Res | N-substituted pyridone and general method for preparing pyridones |
| JPH06505239A (ja) * | 1991-01-31 | 1994-06-16 | ワーナー−ランバート・コンパニー | 抗炎症剤として有用な４，６−ジ−第三ブチル−５−ヒドロキシ−１，３−ピリミジンの置換されたヘテロアリール類似体 |
| JPWO2002085858A1 (ja) * | 2001-04-20 | 2004-08-12 | 旭硝子株式会社 | 精製されたピペリジン誘導体の製造方法 |
| JP4342940B2 (ja) * | 2001-08-06 | 2009-10-14 | 塩野義製薬株式会社 | ５−メチル−１−フェニル−２（１ｈ）ピリジノンの製造方法 |
| CN1218942C (zh) | 2002-06-11 | 2005-09-14 | 中南大学湘雅医学院 | 抗纤维化吡啶酮化合物及其生产工艺方法 |
| CN100396669C (zh) * | 2006-03-15 | 2008-06-25 | 浙江省医学科学院 | 一种抗纤维化药物吡非尼酮的制备方法 |
| MX2007006349A (es) | 2007-05-29 | 2009-02-18 | Cell Therapy And Technology S | Nuevo proceso de sintesis para la obtencion de 5-metil-1-fenil-2-(ih)-piridona, composicion y uso de la misma. |
| WO2008157786A1 (en) * | 2007-06-20 | 2008-12-24 | Auspex Pharmaceutical, Inc. | Substituted n-aryl pyridinones as fibrotic inhibitors |
| US20090131485A1 (en) * | 2007-09-10 | 2009-05-21 | Concert Pharmaceuticals, Inc. | Deuterated pirfenidone |
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