WO2007010557A2 - Methode de preparation de ropinirole tres pur - Google Patents

Methode de preparation de ropinirole tres pur Download PDF

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Publication number
WO2007010557A2
WO2007010557A2 PCT/IN2006/000256 IN2006000256W WO2007010557A2 WO 2007010557 A2 WO2007010557 A2 WO 2007010557A2 IN 2006000256 W IN2006000256 W IN 2006000256W WO 2007010557 A2 WO2007010557 A2 WO 2007010557A2
Authority
WO
WIPO (PCT)
Prior art keywords
ropinirole
process according
formula
amino compound
salt
Prior art date
Application number
PCT/IN2006/000256
Other languages
English (en)
Other versions
WO2007010557A3 (fr
Inventor
Chidambaram Venkateswaran Srinivasan
Husain Siddiqui Shrat
Original Assignee
Ind-Swift Laboratorie Limted
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 Ind-Swift Laboratorie Limted filed Critical Ind-Swift Laboratorie Limted
Publication of WO2007010557A2 publication Critical patent/WO2007010557A2/fr
Publication of WO2007010557A3 publication Critical patent/WO2007010557A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/32—Oxygen atoms
    • C07D209/34—Oxygen atoms in position 2

Definitions

  • the field of the invention relates to highly pure ropinirole or salt thereof and a process for preparing highly pure ropinirole of structural Formula I,
  • Ropinirole of Formula-I chemically known as 4-[2-(di-n-propylammo)-ethyl]- 2(3H)-indolone and is useful in the treatment of Parkinsons disease.
  • Ropinirole has been first disclosed in US patent 4,452,808.
  • the present invention provides a process for the preparation of highly pure ropinirole where starting material converts to final product in more than 97%.
  • substantially pure ropinirole or a salt thereof having amino compound less than 0.05% in another general aspect there is provided substantially pure ropinirole or a salt thereof having amino compound less than 0.05%.
  • a process for the preparation of substantially pure ropinirole or a salt thereof includes reducing nitro compound of Formula II with a reducing agent to produce amino compound of Formula III, cyclizing the resulting amino compound in situ using palladium on carbon in the presence of aqueous alcoholic medium and isolating the substantially pure ropinirole or a salt thereof by simple isolation method of extraction and acid base treatment.
  • the reducing agent may be palladium on carbon.
  • the inventors have developed an efficient process for the preparation of substantially pure ropinirole or a salt thereof, by reducing nitro compound of Formula II with a reducing agent to produce amino compound, 2-amino-6-(2-di- n-propylaminoethyl)-phenylacetic acid of Formula III and cyclizing in situ the amino compound of Formula III in aqueous alcoholic medium and isolating substantially pure ropinirole or a salt thereof by simple isolation method of extraction and acid base treatment.
  • the 2 ⁇ nitro-6-(2-di-n-propylaminoethyl)-phenylacetic acid hydrochloride of formula II may be treated with a reducing agent in the presence of alcoholic solvent.
  • the reaction is performed in an autoclave at a temperature between 25° -5O 0 C and preferably at 35° -4O 0 C under hydrogen pressure of 3.0 kg/cm 2 for 5 hours. It is advantageous to add some water in the reaction mass to complete cyclization of the resulting amino compound i.e. up to 98% conversion.
  • the progress of reaction is monitored by HPLC.
  • the reducing agent includes any reducing agent which is capable of carrying out the reduction of the nitro group, including, for example, palladium oh carbon, and the like and preferably palladium on carbon is used.
  • the alcoholic solvent may include one or more of primary, secondary and tertiary alcohol having from one to six carbon atoms.
  • the alcoholic solvent may include one or more of methanol, ethanol, n-propanol, isopropanol, isobutanol, n-butanol and t-butanol. Tn particular, the alcoholic solvent is preferably ethanol. Mixtures of all of these solvents are also contemplated.
  • solvent aqueous alcohol
  • product may be slurred in acetonitrile, isopropyl ether, ethyl acetate and chlorinated solvent such as methylene chloride, chloroform and the like.
  • resulting solid may take in water and basified with sodium hydroxide and product is extracted in organic solvent such as isopropyl ether, ethyl acetate and chlorinated solvent such as methylene chloride, chloroform and the like.
  • organic layer is optionally distilled to 60-70% with respect to its original volume.
  • the hydrochloride salt of Ropinirole is prepared by treating the ; organic layer with ethanolic-HCl at ambient temperature.
  • the product is isolated in high purity and high yield.
  • the compound can be optionally recrystallized from alcohol to improve colour if required.
  • the product so obtained is having purity greater than 99.5% by HPLC, and preferably greater than 99.8%.
  • reaction mass was filtered and ethyl alcohol was recovered completely under vacuum at temperature 40°-45°C.
  • Ethyl alcohol (300 ml) was added and recovered under same conditions.
  • Ethyl alcohol (300 ml) was added to the dried mass and stirred for 30-45 min at 40° - 45 0 C then cooled at 15-2O 0 C and stirred at 15° - 20 0 C for 45 min. and filter.
  • the wet cake was slurred in acetonitrile (500 ml) and stirred for 30 min at 35° - 4O 0 C then cooled to 15 - 2O 0 C.
  • the cooled mass was filter and slurry washed with di- isopropyl ether (300 ml).
  • the wet cake was added to D M water (120 ml), sodium hydroxide solution 2 % (400 ml) and isopropyl ether (900 ml) were added and stirred at 15° - 2O 0 C for 10 -15 min.
  • the organic layer was separated and aqueous layer was extracted with isopropyl ether (2 x 250 ml).
  • the combined organic layer was washed with chilled sodium hydroxide solution 1%, (200 ml) filtered by brine (200 ml) and heat to recover isopropyl ether (60 - 70%) was recovered under vacuum.
  • reaction mass was cooled at 15° -20 ⁇ C and pH was adjusted to 1.5 - 2.5 with ethanolic hydrochloric acid (20 - 25%, 30 ml) and was stirred 30-40 min at 20° -25 0 C.
  • the product obtained was centrifuged and slurry washed with absolute alcohol (200 ml).
  • the wet material was dried under vacuum for 7 - 8 hr to obtain 57 g (66.80%) of title compound having purity of 99.30% by HPLC

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Indole Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

La présente invention concerne un ropinirole très pur ou son sel, et une méthode de préparation d'un ropinirole très pur de formule (I). La méthode consiste à réduire un composé nitro de formule (II) et à cycliser in situ le composé amino résultant en utilisant du palladium sur du carbone en présence d'un milieu alcoolique aqueux.
PCT/IN2006/000256 2005-07-22 2006-07-19 Methode de preparation de ropinirole tres pur WO2007010557A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1920DE2005 2005-07-22
IN1920/DEL/2005 2005-07-22

Publications (2)

Publication Number Publication Date
WO2007010557A2 true WO2007010557A2 (fr) 2007-01-25
WO2007010557A3 WO2007010557A3 (fr) 2007-11-22

Family

ID=37669240

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2006/000256 WO2007010557A2 (fr) 2005-07-22 2006-07-19 Methode de preparation de ropinirole tres pur

Country Status (1)

Country Link
WO (1) WO2007010557A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010091128A2 (fr) 2009-02-04 2010-08-12 Qualcomm Incorporated Procédés et systèmes de programmation parmi des noeuds pour un intervalle de données dans des réseaux de communication sans fil

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4452808A (en) * 1982-12-07 1984-06-05 Smithkline Beckman Corporation 4-Aminoalkyl-2(3H)-indolones

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4452808A (en) * 1982-12-07 1984-06-05 Smithkline Beckman Corporation 4-Aminoalkyl-2(3H)-indolones

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010091128A2 (fr) 2009-02-04 2010-08-12 Qualcomm Incorporated Procédés et systèmes de programmation parmi des noeuds pour un intervalle de données dans des réseaux de communication sans fil

Also Published As

Publication number Publication date
WO2007010557A3 (fr) 2007-11-22

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