WO2005049560A2 - Procede de preparation d'un compose antidepresseur - Google Patents

Procede de preparation d'un compose antidepresseur Download PDF

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Publication number
WO2005049560A2
WO2005049560A2 PCT/IN2004/000301 IN2004000301W WO2005049560A2 WO 2005049560 A2 WO2005049560 A2 WO 2005049560A2 IN 2004000301 W IN2004000301 W IN 2004000301W WO 2005049560 A2 WO2005049560 A2 WO 2005049560A2
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WO
WIPO (PCT)
Prior art keywords
formula
compound
preparation
foπnula
stir
Prior art date
Application number
PCT/IN2004/000301
Other languages
English (en)
Other versions
WO2005049560A3 (fr
Inventor
Vijaykumar Muljibhai Patel
Riteshkumar Rajnikant Kansara
Nishchal Vinodbhai Patel
Rajeev Budhdev Rehani
Rajamannar Thennati
Original Assignee
Sun Pharmaceutical Industries 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 Sun Pharmaceutical Industries Limited filed Critical Sun Pharmaceutical Industries Limited
Publication of WO2005049560A2 publication Critical patent/WO2005049560A2/fr
Publication of WO2005049560A3 publication Critical patent/WO2005049560A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
    • C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/64—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms
    • C07C217/66—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain
    • C07C217/70—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains further substituted by singly-bound oxygen atoms with singly-bound oxygen atoms and six-membered aromatic rings bound to the same carbon atom of the carbon chain linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Definitions

  • the present invention relates to a process for the preparation of anti-depressant compound of fo ⁇ nula I.
  • Formula I Compound of formula I, with a chemical name l-[2-(dimethylamino)-l-(4- methoxyphenyl)ethyl] cyclohexanol , is commonly known as venlafaxme (INN Name).
  • the process of the present invention uses a reducing agent which is easy to handle and store and yields about 65% compound of formula I or its pharmaceutically acceptable salt, substantially free of compound of formula IV.
  • the patent '186 also discloses the process of the preparation of compound of formula lib by reacting 4-methoxyphenylacetonitrile with cyclohexanone in dry THF in the presence of n-butyl lithium in hexane at -70°C to -50°C resulting in only about 30% yield. Further, this process uses an expensive, hazardous, extremely reactive and relatively unstable reagent vfe.n-butyl lithium or lithiumdiisopropylamide. These drawbacks along with sub-zero operating temperatures and requirement of anhydrous conditions makes this process commercially unviable.
  • the process.of the-present_ invention is carried out in the presence of a commonly available, inexpensive base and a cation solvating agent, employing normal reaction conditions which does not require absolute anhydrous conditions and furnishes yields upto 60%.
  • Formula lib lib by reacting 4-methoxyphenylacetonitrile with cyclohexanone in the presence of a base such as sodium or potassium hydroxide at 0 to 15°C in water.
  • a base such as sodium or potassium hydroxide
  • This patent does not describe the preparation of compound of formula lib in the presence of a cation solvating agent , at easily operable temperature. Further, the product is crystallised so as to get the pure compound of formula lib.
  • the process of the present invention provides compound of formula lib which is substantially pure.
  • the process of the present invention is carried out at convenient operating temperature of 18 to 85°C which overcomes the drawbacks of the above prior art and yields compound of formula lib in substantially pure form which does not require purification before being processed by conventional means to compound of formula I.
  • the process of the present invention circumvents the above drawbacks.
  • the base employed in the present invention like alkaline earth metal salts are comparatively milder bases which would suppress the formation of side product , an amide, resulting from the hydrolysis of nitrile, which could form when strong bases like Sodium, potassium hydroxide as suggested in WO 0218325, are used during the addition reaction of aryl acetonitiriles to cyclohexanone, under the specified conditions.
  • the object of the present invention is to provide a convenient, commercially viable process for the preparation of compound of formula I.
  • the present invention provides a process for the preparation of anti-depressant, compound of formula I, or its pharmaceutically acceptable salts, formula I said process comprising reducing compound of fo ⁇ nula Ila,
  • compound of fo ⁇ nula I may be prepared by a process comprising (a) reacting compound of formula HI with cyclohexanone in the presence of base and cation solvating agent in an aprotic organic solvent to obtain compound of formula lib; and
  • the present invention describes process for the preparation of compound of formula I from compound of fo ⁇ nula II
  • Compound of formula Ila may be reduced to yield compound of formula I.
  • the reduction may be ca ⁇ ied out with a mild reducing agent such as sodium bis(2- methoxyethoxy) aluminium hydride.
  • a mild reducing agent such as sodium bis(2- methoxyethoxy) aluminium hydride.
  • Sodium bis(2-methoxyethoxy) aluminium hydride or red-Al reagent is commercially available as 70% solution in Toluene (Ester x solution ® ) which is easy to store and handle.
  • the freely solvent soluble Aluminum hydride viz. sodium bis(2-methoxyethoxy) aluminium hydride facilitates the formation of soluble Aluminium complex with the substrate and its relatively mild nature ensues in its selectivity towards reducing amide functionality.
  • the process of '186 reduces compound of fo ⁇ nula Ila with lithium aluminum hydride.
  • Lithium aluminum hydride being highly reactive towards alcohols, generates the heterogeneous aluminium alkoxide of the tertiary alcohol, thus posing potential problems of retroaldol type reaction to get an impurity, a compound of formula ry, during synthesis of compound of formula I.
  • compound of formula Ila is reduced at temperature about 0 to 10°C, preferably about 0 to 5°C.
  • the process for preparing compound of Formula I or its pharmaceutically acceptable salts comprises
  • the base may be selected from organic or inorganic base, preferably inorganic base.
  • the inorganic base may be selected from alkali or alkaline earth metal salts such as carbonates or oxides of sodium, potassium, lithium, magnesium, calcium or barium and the like or their mixtures, most preferred being potassium carbonate.
  • the cation solvating agent may be selected from hexamine,
  • the aprotic organic solvent may be selected from amides, nitriles, hydrocarbons, halogenated hydrocarbons, aromatic solvents, ethers, dimethylsulphoxide or mixtures thereof
  • the reaction of compound of formula III with cyclohexanone may be ca ⁇ ied out at temperatures ranging from 0 to 100°C, preferably 18 to 85°C.
  • the reaction time may range from about 2 to 6 hours.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé de préparation d'un composé antidépresseur représenté par la formule (I) ou de ses sels acceptables sur le plan pharmaceutique. Ce procédé consiste à réduire un composé de formule (IIa) avec un hydrure de bis(2-méthoxyéthoxy) aluminium de sodium suivi d'une formation éventuelle de sel. Dans la formule (IIa), R représente CONMe2.
PCT/IN2004/000301 2003-09-29 2004-09-28 Procede de preparation d'un compose antidepresseur WO2005049560A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1022/MUM/2003 2003-09-29
IN1022MU2003 2003-09-29

Publications (2)

Publication Number Publication Date
WO2005049560A2 true WO2005049560A2 (fr) 2005-06-02
WO2005049560A3 WO2005049560A3 (fr) 2005-09-15

Family

ID=34611197

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2004/000301 WO2005049560A2 (fr) 2003-09-29 2004-09-28 Procede de preparation d'un compose antidepresseur

Country Status (1)

Country Link
WO (1) WO2005049560A2 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008013990A2 (fr) * 2006-07-26 2008-01-31 Teva Pharmaceutical Industries Ltd. Procédé pour synthétiser le composé o-desméthylvenlafaxine
WO2008093142A1 (fr) * 2007-01-31 2008-08-07 Generics [Uk] Limited Procede de preparation de o-desmethyl venlafaxine
US7674935B2 (en) 2006-04-17 2010-03-09 Teva Pharmaceutical Industries Ltd. Crystal forms of O-desmethylvenlafaxine
US8569371B2 (en) 2010-03-29 2013-10-29 Pliva Hrvatska D.O.O. Crystal forms of O-desmethylvenlafaxine fumarate
CN109535017A (zh) * 2018-12-29 2019-03-29 合肥立方制药股份有限公司 一种盐酸文拉法辛制备方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0112669A2 (fr) * 1982-12-13 1984-07-04 American Home Products Corporation Dérivés de phényléthylamines et leurs produits intermédiaires
CN1240206A (zh) * 1999-06-17 2000-01-05 华东理工大学 1－[2－(二甲氨基)－1－(4－甲氧基苯基)乙基]环已醇盐酸盐的制备方法
EP1238967A1 (fr) * 2001-02-28 2002-09-11 Council of Scientific and Industrial Research Procédé de préparation du 1-(cyano(aryl)méthyl)cyclohexanol
WO2003000652A1 (fr) * 2001-06-22 2003-01-03 Wyeth Procede de preparation de derives de cyclohexanol
KR20030065889A (ko) * 2002-02-01 2003-08-09 에스케이 주식회사 고수율로 벤라팩신 중간체를 연속적으로 제조하는 방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0112669A2 (fr) * 1982-12-13 1984-07-04 American Home Products Corporation Dérivés de phényléthylamines et leurs produits intermédiaires
CN1240206A (zh) * 1999-06-17 2000-01-05 华东理工大学 1－[2－(二甲氨基)－1－(4－甲氧基苯基)乙基]环已醇盐酸盐的制备方法
EP1238967A1 (fr) * 2001-02-28 2002-09-11 Council of Scientific and Industrial Research Procédé de préparation du 1-(cyano(aryl)méthyl)cyclohexanol
WO2003000652A1 (fr) * 2001-06-22 2003-01-03 Wyeth Procede de preparation de derives de cyclohexanol
KR20030065889A (ko) * 2002-02-01 2003-08-09 에스케이 주식회사 고수율로 벤라팩신 중간체를 연속적으로 제조하는 방법

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7674935B2 (en) 2006-04-17 2010-03-09 Teva Pharmaceutical Industries Ltd. Crystal forms of O-desmethylvenlafaxine
WO2008013990A2 (fr) * 2006-07-26 2008-01-31 Teva Pharmaceutical Industries Ltd. Procédé pour synthétiser le composé o-desméthylvenlafaxine
WO2008013990A3 (fr) * 2006-07-26 2008-03-27 Teva Pharma Procédé pour synthétiser le composé o-desméthylvenlafaxine
US7605290B2 (en) 2006-07-26 2009-10-20 Teva Pharmaceutical Industries Ltd. Processes for the synthesis of O-desmethylvenlafaxine
KR101019455B1 (ko) * 2006-07-26 2011-03-07 테바 파마슈티컬 인더스트리즈 리미티드 Ｏ-데스메틸벤라팍신의 합성 방법
WO2008093142A1 (fr) * 2007-01-31 2008-08-07 Generics [Uk] Limited Procede de preparation de o-desmethyl venlafaxine
US8569371B2 (en) 2010-03-29 2013-10-29 Pliva Hrvatska D.O.O. Crystal forms of O-desmethylvenlafaxine fumarate
CN109535017A (zh) * 2018-12-29 2019-03-29 合肥立方制药股份有限公司 一种盐酸文拉法辛制备方法
CN109535017B (zh) * 2018-12-29 2023-08-08 合肥立方制药股份有限公司 一种盐酸文拉法辛制备方法

Also Published As

Publication number Publication date
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