WO2009054004A2 - Nouveau procédé pour la préparation du sorafénib - Google Patents

Nouveau procédé pour la préparation du sorafénib Download PDF

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Publication number
WO2009054004A2
WO2009054004A2 PCT/IN2008/000698 IN2008000698W WO2009054004A2 WO 2009054004 A2 WO2009054004 A2 WO 2009054004A2 IN 2008000698 W IN2008000698 W IN 2008000698W WO 2009054004 A2 WO2009054004 A2 WO 2009054004A2
Authority
WO
WIPO (PCT)
Prior art keywords
formula
sorafenib
compound
reaction
sodium
Prior art date
Application number
PCT/IN2008/000698
Other languages
English (en)
Other versions
WO2009054004A3 (fr
Inventor
Muddasani Pulla Reddy
Nannapaneni Venkaiah Chowdary
Original Assignee
Natco Pharma Limited
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Natco Pharma Limited filed Critical Natco Pharma Limited
Publication of WO2009054004A2 publication Critical patent/WO2009054004A2/fr
Publication of WO2009054004A3 publication Critical patent/WO2009054004A3/fr

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Classifications

    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides

Definitions

  • Present invention relates to a novel and improved process for the preparation of sorafenib (4-(4-(3-(4-chloro-3-(trifluoromethyl)phenyl)ureido)phenoxy)-N-methylpicolinamide) of formula I involving a novel intermediate of formula II.
  • Compound of formula II is a key intermediate used in the synthesis of sorafenib of formula I.
  • Sorafenib is a multiple kinase inhibitor targeting both RAF kinase and receptor tyrosine kinase that promote angiogenesis. Clinical development of sorafenib is reviewed in Expert Opin. Pharmacother.., 7, 453-461 (2006). Sorafenib is available in the market as tosylate salt under the brand name Nexavar.
  • Sorafenib and its pharmaceutically acceptable salts and solvates are reported for the first time in WO0041698 (corresponding US 03139605) by Bayer.
  • WO0041698 corresponding US 03139605
  • picolinic acid of formula III is reacted with thionyl chloride to give the 4-chloro derivative which on treatment
  • a scalable process for the preparation of sorafenib is disclosed in WO2006034796.
  • chemistry is used in making sorafenib of formula I.
  • catalytic quantity. of DMF used in the prior art process is replaced with reagents like hydrogen bromide, thionyl bromide and sodium bromide. Yield of required product remained same without any advantages from newly introduced corrosive reagents.
  • Process improvements like change of solvents, reagents, etc were applied in subsequent steps making the process scalable.
  • Overall yield of sorafenib is increased to 74% from the prior art 63% yield. Purity of sorafenib is only 95% and was obtained as light brown colored solid.
  • the main objective of the present invention is to provide an improved process for the preparation of sorafenib, which is commercially applicable.
  • R C 1 -C 8 alkyl
  • ester compound of formula X is reacted with ester derivative of formula XI in the presence of a base in a solvent medium to get novel esters of formula XII.
  • Reaction of ester compound of formula XII with methylamine yielded the required sorafenib of formula I.
  • process of the present invention provides a novel process for the preparation of sorafenib of formula I,
  • the isocyanate of formula VIII is reacted with 4-aminophenol of formula IX or its acid addition salt in the presence of a solvent, inert towards isocyante at a temperature above 15°C.
  • a neutralizing agent such as triethylamine, inert towards isocyanate is used to liberate the base.
  • compound of formula X is reacted with compound of formula XI in a solvent such as DMF, DMAc, DMSO, THF, dioxane, toluene, cyclohexane, acetonitrile.
  • Base used in the reaction is selected from sodium or potassium alcoholate or sodium or potassium hydroxide, carbonate, bicarbonate, sodium hydride, etc. Temperature of the reaction is in the range of 25-120°C.
  • compound of formula VI is prepared from 2-picolinic acid of formula HL 2-Picolinic acid of formula III is reacted with thionyl chloride in the presence of catalytic amount of DMF and in a solvent medium at 60-80°C to get the acid chloride of formula IV.
  • the acid chloride of formula IV thus obtained is reacted in situ with an alcohol to get the corresponding ester derivative of formula XI.
  • the ester derivative of formula XI is reacted with methanolic methylamine to get the corresponding amide of formula VI.
  • sorafenib base is produced in more than 80% yield with more than 99% purity by HPLC.
  • Present invention provides novel compound of formula X.
  • the crude compound (4.7 g) was dissolved in 10 ml of IPA and added 1.9 g of p- toluenesulfonic acid.
  • the reaction mass was stirred at RT for 15 h and filtered.
  • the wet solid was washed with 10 ml of IPA and dried at 50-60°C to get 3.4 g of title compound as off-white crystalline solid.

Abstract

Cette invention concerne un procédé, nouveau et amélioré, pour la préparation du sorafénib, (4-(4-(3-(4-chloro-3-(trifluorométhyl)phényl)uréido)- phénoxy)-N-méthyl-picolinamide) de formule I, qui implique un nouvel intermédiaire de formule II, à titre d'intermédiaire clé. Le tosylate de sorafénib, commercialisé sous le nom de Nexavar, est un inhibiteur de kinases multiples ciblant à la fois la kinase RAF et la tyrosine kinase des récepteurs qui favorisent l'angiogenèse.
PCT/IN2008/000698 2007-10-22 2008-10-22 Nouveau procédé pour la préparation du sorafénib WO2009054004A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2372CH2007 2007-10-22
IN2372/CHE/2007 2007-10-22

Publications (2)

Publication Number Publication Date
WO2009054004A2 true WO2009054004A2 (fr) 2009-04-30
WO2009054004A3 WO2009054004A3 (fr) 2009-07-02

Family

ID=40527499

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2008/000698 WO2009054004A2 (fr) 2007-10-22 2008-10-22 Nouveau procédé pour la préparation du sorafénib

Country Status (1)

Country Link
WO (1) WO2009054004A2 (fr)

Cited By (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7838541B2 (en) 2002-02-11 2010-11-23 Bayer Healthcare, Llc Aryl ureas with angiogenesis inhibiting activity
US7897623B2 (en) 1999-01-13 2011-03-01 Bayer Healthcare Llc ω-carboxyl aryl substituted diphenyl ureas as p38 kinase inhibitors
WO2011036648A1 (fr) 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Polymorphes de sels d'addition acide de sorafénib
WO2011036647A1 (fr) 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Procédé de préparation de tosylate de sorafénib
WO2011058522A1 (fr) 2009-11-12 2011-05-19 Ranbaxy Laboratories Limited Sel d'ethylsulfonate de sorafenib et son procede de preparation
WO2011092663A2 (fr) 2010-01-29 2011-08-04 Ranbaxy Laboratories Limited Solvate de diméthylsulfoxyde du 4-(4-{3-[4-chloro-3-(trifluorométhyl)phényl]uréido}phénoxy)-n2-méthylpyridine-2-carboxamide
WO2011113367A1 (fr) * 2010-03-18 2011-09-22 苏州泽璟生物制药有限公司 Méthode et procédés de préparation et de production de ω-diphénylurée deutérée
US8124630B2 (en) 1999-01-13 2012-02-28 Bayer Healthcare Llc ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
CN103408488A (zh) * 2013-08-13 2013-11-27 张家港威胜生物医药有限公司 一种索拉非尼的优化合成方法
US8796250B2 (en) 2003-05-20 2014-08-05 Bayer Healthcare Llc Diaryl ureas for diseases mediated by PDGFR
CN104177292A (zh) * 2014-08-08 2014-12-03 亿腾药业（泰州）有限公司 一种工业化生产甲苯磺酸索拉非尼多晶型ⅰ的方法
WO2015031604A1 (fr) 2013-08-28 2015-03-05 Crown Bioscience, Inc. Signatures d'expression génique permettant de prédire la réponse d'un sujet à un inhibiteur multikinase et leurs procédés d'utilisation
CN104761492A (zh) * 2014-01-03 2015-07-08 正大天晴药业集团股份有限公司 对甲苯磺酸索拉非尼的晶型及其制备方法
CN105399668A (zh) * 2015-12-29 2016-03-16 开封制药(集团)有限公司 一种“一锅法”制备索拉菲尼的方法
CN105481764A (zh) * 2014-09-16 2016-04-13 重庆圣华曦药业股份有限公司 一种索拉非尼对甲苯磺酸盐的制备方法
CN105801475A (zh) * 2016-04-25 2016-07-27 华润双鹤利民药业（济南）有限公司 一种甲苯磺酸索拉非尼的制备方法
CN109796400A (zh) * 2017-11-16 2019-05-24 四川科伦药物研究院有限公司 一种甲苯磺酸索拉菲尼晶型及其制备方法
WO2020160453A1 (fr) * 2019-01-31 2020-08-06 Ionis Pharmaceuticals, Inc. Modulateurs de l'expression de yap1

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JPH0848078A (ja) * 1994-08-05 1996-02-20 Nippon Paper Ind Co Ltd 感熱記録体
WO2000041698A1 (fr) * 1999-01-13 2000-07-20 Bayer Corporation DIPHENYLE UREES A SUBSTITUTION φ-CARBOXY ARYLE EN TANT QU'INHIBITEURS DE LA KINASE p38
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JPH0848078A (ja) * 1994-08-05 1996-02-20 Nippon Paper Ind Co Ltd 感熱記録体
WO2000041698A1 (fr) * 1999-01-13 2000-07-20 Bayer Corporation DIPHENYLE UREES A SUBSTITUTION φ-CARBOXY ARYLE EN TANT QU'INHIBITEURS DE LA KINASE p38
WO2000042012A1 (fr) * 1999-01-13 2000-07-20 Bayer Corporation DIPHENYLUREES A SUBSTITUANTS φ-CARBOXYARYLES, INHIBITRICES DE KINASE RAF
WO2003068228A1 (fr) * 2002-02-11 2003-08-21 Bayer Pharmaceuticals Corporation Urees aryliques a activite inhibitrice d'angiogenese
EP1683785A1 (fr) * 2003-11-11 2006-07-26 Eisai Co., Ltd. Derive d'uree et son procede de production
WO2006034796A1 (fr) * 2004-09-29 2006-04-06 Bayer Healthcare Ag Procede de preparation de 4-{4-[({[4-chloro-3-(trifluoromethyl)phenyl]amino}carbonyl)amino]phenoxy}-n-methylpyridine-2-carboxamide

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Title
D. BANKSTON ET AL.: "A Scalable Synthesis of BAY 43-9006: A Potent Raf Kinase Inhibitor for the Treatment of Cancer" ORGANIC PROCESS RESEARCH & DEVELOPMENT, vol. 6, no. 6, 2002, pages 777-781, XP002523918 cited in the application *
PAN W ET AL: "Pyrimido-oxazepine as a versatile template for the development of inhibitors of specific kinases" BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, PERGAMON, ELSEVIER SCIENCE, GB, vol. 15, no. 24, 15 December 2005 (2005-12-15), pages 5474-5477, XP025314229 ISSN: 0960-894X [retrieved on 2005-12-15] *

Cited By (37)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7897623B2 (en) 1999-01-13 2011-03-01 Bayer Healthcare Llc ω-carboxyl aryl substituted diphenyl ureas as p38 kinase inhibitors
US8124630B2 (en) 1999-01-13 2012-02-28 Bayer Healthcare Llc ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US8841330B2 (en) 1999-01-13 2014-09-23 Bayer Healthcare Llc Omega-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
US7838541B2 (en) 2002-02-11 2010-11-23 Bayer Healthcare, Llc Aryl ureas with angiogenesis inhibiting activity
US8618141B2 (en) 2002-02-11 2013-12-31 Bayer Healthcare Llc Aryl ureas with angiogenesis inhibiting activity
US8242147B2 (en) 2002-02-11 2012-08-14 Bayer Healthcare Llc Aryl ureas with angiogenisis inhibiting activity
US8796250B2 (en) 2003-05-20 2014-08-05 Bayer Healthcare Llc Diaryl ureas for diseases mediated by PDGFR
WO2011036647A1 (fr) 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Procédé de préparation de tosylate de sorafénib
WO2011036648A1 (fr) 2009-09-24 2011-03-31 Ranbaxy Laboratories Limited Polymorphes de sels d'addition acide de sorafénib
US8609854B2 (en) 2009-09-24 2013-12-17 Ranbaxy Laboratories Limited Process for the preparation of sorafenib tosylate
US8604208B2 (en) 2009-09-24 2013-12-10 Ranbaxy Laboratories Limited Polymorphs of sorafenib acid addition salts
US8552197B2 (en) 2009-11-12 2013-10-08 Ranbaxy Laboratories Limited Sorafenib ethylsulfonate salt, process for preparation and use
WO2011058522A1 (fr) 2009-11-12 2011-05-19 Ranbaxy Laboratories Limited Sel d'ethylsulfonate de sorafenib et son procede de preparation
US8618305B2 (en) 2010-01-29 2013-12-31 Ranbaxy Laboratories Limited Sorafenib dimethyl sulphoxide solvate
WO2011092663A3 (fr) * 2010-01-29 2011-12-29 Ranbaxy Laboratories Limited Solvate de diméthylsulfoxyde du 4-(4-{3-[4-chloro-3-(trifluorométhyl)phényl]uréido}phénoxy)-n2-méthylpyridine-2-carboxamide
WO2011092663A2 (fr) 2010-01-29 2011-08-04 Ranbaxy Laboratories Limited Solvate de diméthylsulfoxyde du 4-(4-{3-[4-chloro-3-(trifluorométhyl)phényl]uréido}phénoxy)-n2-méthylpyridine-2-carboxamide
AU2011210326B2 (en) * 2010-01-29 2014-10-09 Sun Pharmaceutical Industries Limited Sorafenib dimethyl sulphoxide solvate
US9078933B2 (en) 2010-03-18 2015-07-14 Suzhou Zelgen Biopharmaceutical Co., Ltd. Deuterated omega diphenylurea related compounds and intermediates
JP2013522244A (ja) * 2010-03-18 2013-06-13 ▲蘇▼州▲澤▼▲ジン▼生物制▲薬▼有限公司 フッソ含有重水素化ジフェニル尿素の製造方法
JP2013522243A (ja) * 2010-03-18 2013-06-13 ▲蘇▼州▲澤▼▲ジン▼生物制▲薬▼有限公司 重水素化ω−ジフェニル尿素の合成及び生産の方法並びにプロセス
CN102803222A (zh) * 2010-03-18 2012-11-28 苏州泽璟生物制药有限公司 一种氘代的ω-二苯基脲的合成及生产的方法和工艺
US8669369B2 (en) 2010-03-18 2014-03-11 Suzhou Zelgen Biopharmaceutical Co., Ltd. Method and process for preparation and production of deuterated Ω-diphenylurea
WO2011113367A1 (fr) * 2010-03-18 2011-09-22 苏州泽璟生物制药有限公司 Méthode et procédés de préparation et de production de ω-diphénylurée deutérée
EP3330254A3 (fr) * 2010-03-18 2018-08-22 Suzhou Zelgen Biopharmaceutical Co., Ltd. Procédé et processus de préparation et de production d'omega-diphénylurée deutérée
JP2015091845A (ja) * 2010-03-18 2015-05-14 ▲蘇▼州▲澤▼▲ジン▼生物制▲薬▼有限公司 ４−（４−（３−（４−クロロ−３−（トリフルオロメチル）フェニル）ウレイド）−フェノキシ）−Ｎ−（１’，１’，１’−トリデューテロメチル）ピコリンアミドのｐ−トルエンスルホン酸塩（ＣＭ４３０７・ＴｓＯＨ）、ＣＭ４３０７・ＴｓＯＨの製造方法、及びＣＭ４３０７・ＴｓＯＨを含有する医薬的組成物
CN103408488A (zh) * 2013-08-13 2013-11-27 张家港威胜生物医药有限公司 一种索拉非尼的优化合成方法
WO2015031604A1 (fr) 2013-08-28 2015-03-05 Crown Bioscience, Inc. Signatures d'expression génique permettant de prédire la réponse d'un sujet à un inhibiteur multikinase et leurs procédés d'utilisation
CN104761492A (zh) * 2014-01-03 2015-07-08 正大天晴药业集团股份有限公司 对甲苯磺酸索拉非尼的晶型及其制备方法
CN104177292A (zh) * 2014-08-08 2014-12-03 亿腾药业（泰州）有限公司 一种工业化生产甲苯磺酸索拉非尼多晶型ⅰ的方法
CN105481764A (zh) * 2014-09-16 2016-04-13 重庆圣华曦药业股份有限公司 一种索拉非尼对甲苯磺酸盐的制备方法
CN105399668A (zh) * 2015-12-29 2016-03-16 开封制药(集团)有限公司 一种“一锅法”制备索拉菲尼的方法
CN105801475A (zh) * 2016-04-25 2016-07-27 华润双鹤利民药业（济南）有限公司 一种甲苯磺酸索拉非尼的制备方法
CN105801475B (zh) * 2016-04-25 2018-01-12 华润双鹤利民药业（济南）有限公司 一种甲苯磺酸索拉非尼的制备方法
CN109796400A (zh) * 2017-11-16 2019-05-24 四川科伦药物研究院有限公司 一种甲苯磺酸索拉菲尼晶型及其制备方法
CN109796400B (zh) * 2017-11-16 2022-07-29 四川科伦药物研究院有限公司 一种甲苯磺酸索拉菲尼晶型及其制备方法
WO2020160453A1 (fr) * 2019-01-31 2020-08-06 Ionis Pharmaceuticals, Inc. Modulateurs de l'expression de yap1
US11214803B2 (en) 2019-01-31 2022-01-04 Ionis Pharmaceuticals, Inc. Modulators of YAP1 expression

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