WO2005019170A1 - Nouveau procede de preparation de sel de sodium d'acide 7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl]-3, 5-dihydroxy-6-heptenoique - Google Patents

Nouveau procede de preparation de sel de sodium d'acide 7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl]-3, 5-dihydroxy-6-heptenoique Download PDF

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Publication number
WO2005019170A1
WO2005019170A1 PCT/IN2003/000287 IN0300287W WO2005019170A1 WO 2005019170 A1 WO2005019170 A1 WO 2005019170A1 IN 0300287 W IN0300287 W IN 0300287W WO 2005019170 A1 WO2005019170 A1 WO 2005019170A1
Authority
WO
WIPO (PCT)
Prior art keywords
indol
methylethyl
dihydroxy
fluorophenyl
heptenoic acid
Prior art date
Application number
PCT/IN2003/000287
Other languages
English (en)
Inventor
Sumithra Srinath
Tom Thomas Puthiaparampil
Sambasivam Ganesh
Original Assignee
Biocon 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 Biocon Limited filed Critical Biocon Limited
Priority to AU2003269477A priority Critical patent/AU2003269477A1/en
Priority to PCT/IN2003/000287 priority patent/WO2005019170A1/fr
Publication of WO2005019170A1 publication Critical patent/WO2005019170A1/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
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/12—Radicals substituted by oxygen atoms

Definitions

  • the instant invention related to a process for the preparation of 6-Heptenoic acid, 7-[3-(4-fluorophenyl)-l-(l-methylethyl)-lH- indol-2-yl]-3,5-dihydroxy-, sodium salt with high purity.
  • the novel process comprises: a) treating a solution of 7-[3-(4-fluorophenyl)-l-(l- methylethyl)-lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid or its salt, preferably alkali metal salt, with a second to afford an insoluble salt, preferably alkaline earth metal salt, most preferably a calcium salt, b) isolation of the insoluble salt of 7-[3-(4-fluorophenyl)-l-(l- methylethyl)-lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid, c) conversion of the isolated insoluble salt of .
  • the instant invention is related to a process for the preparation of substantially pure 6-Heptenoic acid, 7-[3-(4-fluorophenyl)-l-(l-methylethyl)-lH-indol-2-yl]-3,5- dihydroxy-, sodium salt.
  • the novel process comprises: a) treating a solution of 7-[3-(4-fluorophenyl)-l-(l- methylethyl)-lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid or its salt, preferably alkali metal salt, with a second cation to afford an insoluble salt, preferably alkaline earth metal salt, most preferably a calcium salt, b) isolation of the insoluble salt of 7-[3-(4-fluorophenyl)-l-(l- methylethyl)-lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid, c) conversion of the isolated insoluble salt of 7-[3-(4- fluorophenyl)-l-(l-methylethyl)-lH-indol-2-yl]-3,5-dihydroxy- 6-Heptenoic acid to 7-[3-(4-
  • the novel process comprises: a) treating a solution of 7-[3-(4-fluorophenyl)-l-(l- methylethyl)-lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid or its salt with a divalent cation, b) isolation of the divalent cation salt of 7-[3-(4-fluorophenyl)-l- (l-methylethyl)-lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid, c) conversion of the divalent cation salt of 7-[3-(4- fluorophenyl)-l-(l-methylethyl)-lH-indol-2-yl]-3,5-dihydroxy- 6-Heptenoic acid to 7-[3-(4-fluorophenyl)-l-(l-methylethyl)- lH-in-in
  • 7-[3-(4-fluorophenyl)-l-(l-methylethyl)-lH-indol-2-yl]-3,5- dihydroxy-6-Heptenoic acid or its cation salt can be dissolved or suspended in a suitable solvent.
  • the solvent can be selected from water, water miscible solvent or water immiscible solvent.
  • the salt may be selected from sodium, potassium, ammonium, amine or any other suitable salt of 7-[3-(4-fluorophenyl)-l-(l-methylethyl)- lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid.
  • the mixture can be treated with a second cation or its compound.
  • the second cation exchanges with the first cation to afford an insoluble salt.
  • the newly formed insoluble salt of 7-[3-(4-fluorophenyl)-l-(l- methylethyl)-lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid can be isolated and converted to sodium salt of 7-[3-(4-fluorophenyl)-l-(l- methylethyl)-lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid by treatment with sodium ion or its compound.
  • the process of the present invention results in purification of the 7-[3-(4-fluorophenyl)-l-(l-methylethyl)-lH-indol-2-yl]-3,5- dihydroxy-6-Heptenoic acid and can be isolated and converted to sodium salt of 7-[3-(4-fluorophenyl)-l-(l-methylethyl)-lH-indol-2- yl]-3,5-dihydroxy-6-Heptenoic acid.
  • the process exploits the insoluble nature of the divalent cation salt to isolate the same and effect purification of the 7-[3-(4-fluorophenyl)-l-(l-methylethyl)- lH-indol-2-yl]-3,5-dihydroxy-6-Heptenoic acid.
  • the process of the instant invention is economic since expensive reactants/reagents are not employed.
  • the process of the instant invention is simple since it involves salt formation at ambient conditions. Also it is a highly efficient purification method, as only salt of required product precipitates. All impurities which ido not form salt with second cation remain in the solution, thus resulting in isolation of the product with a high degree of purity.
  • the reaction mixture was concentrated under reduced pressure and water (30 ml) was added to the residue. The solution was further concentrated (volume: 25 ml) and extracted with methyl tert-butyl ether (2 x 15 ml). After adjusting the pH of aqueous layer to 7.0-7.2 by adding aqueous HCI (1.0 N), a solution of calcium acetate (0.6 g, 0.0038 mol) in water (10 ml) was added under stirring at 20-22° C. The reaction mixture was further stirred for 30 minutes to completely precipitate calcium salt of fluvastatin. It was filtered and dried. Pure fluvastatin calcium thus obtained was suspended in water (15 ml) and pH of the mixture was adjusted to 4.0 - 5.0 by adding aqueous HCI (1.5 N).

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Indole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un procédé de préparation de sel de sodium d'acide 7-[3-(4-fluorophényl)-1-(1-méthyléthyl)-1H-indol-2-yl]-3,5-dihydroxy-6-hepténoïque.
PCT/IN2003/000287 2003-08-26 2003-08-26 Nouveau procede de preparation de sel de sodium d'acide 7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl]-3, 5-dihydroxy-6-heptenoique WO2005019170A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
AU2003269477A AU2003269477A1 (en) 2003-08-26 2003-08-26 Novel process for preparation of 7-(3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl)-3, 5-dihydroxy-6-heptenoic acid sodium salt
PCT/IN2003/000287 WO2005019170A1 (fr) 2003-08-26 2003-08-26 Nouveau procede de preparation de sel de sodium d'acide 7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl]-3, 5-dihydroxy-6-heptenoique

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/IN2003/000287 WO2005019170A1 (fr) 2003-08-26 2003-08-26 Nouveau procede de preparation de sel de sodium d'acide 7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl]-3, 5-dihydroxy-6-heptenoique

Publications (1)

Publication Number Publication Date
WO2005019170A1 true WO2005019170A1 (fr) 2005-03-03

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2003/000287 WO2005019170A1 (fr) 2003-08-26 2003-08-26 Nouveau procede de preparation de sel de sodium d'acide 7-[3-(4-fluorophenyl)-1-(1-methylethyl)-1h-indol-2-yl]-3, 5-dihydroxy-6-heptenoique

Country Status (2)

Country Link
AU (1) AU2003269477A1 (fr)
WO (1) WO2005019170A1 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006030304A2 (fr) * 2004-09-17 2006-03-23 Ranbaxy Laboratories Limited Nouvelles formes de sodium de la fluvastatine, leurs procedes de preparation et compositions pharmaceutiques
US20090306117A1 (en) * 2006-04-13 2009-12-10 Vago Pal Rosuvastatin zinc salt

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5354772A (en) * 1982-11-22 1994-10-11 Sandoz Pharm. Corp. Indole analogs of mevalonolactone and derivatives thereof
WO2003016317A1 (fr) * 2001-08-16 2003-02-27 Teva Pharmaceutical Industries Ltd. Procedes permettant de preparer des formes salines calciques de statines

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5354772A (en) * 1982-11-22 1994-10-11 Sandoz Pharm. Corp. Indole analogs of mevalonolactone and derivatives thereof
WO2003016317A1 (fr) * 2001-08-16 2003-02-27 Teva Pharmaceutical Industries Ltd. Procedes permettant de preparer des formes salines calciques de statines

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006030304A2 (fr) * 2004-09-17 2006-03-23 Ranbaxy Laboratories Limited Nouvelles formes de sodium de la fluvastatine, leurs procedes de preparation et compositions pharmaceutiques
WO2006030304A3 (fr) * 2004-09-17 2006-12-07 Ranbaxy Lab Ltd Nouvelles formes de sodium de la fluvastatine, leurs procedes de preparation et compositions pharmaceutiques
US20090306117A1 (en) * 2006-04-13 2009-12-10 Vago Pal Rosuvastatin zinc salt
US9174945B2 (en) * 2006-04-13 2015-11-03 Egis Gyogyszergyar Nyilvanosan Mukodo Reszvenytarsasag Rosuvastatin zinc salt

Also Published As

Publication number Publication date
AU2003269477A1 (en) 2005-03-10

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