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WO2007017720A1 - Processus destine a la preparation d'acitretine - Google Patents

Processus destine a la preparation d'acitretine Download PDF

Info

Publication number
WO2007017720A1
WO2007017720A1 PCT/IB2006/002098 IB2006002098W WO2007017720A1 WO 2007017720 A1 WO2007017720 A1 WO 2007017720A1 IB 2006002098 W IB2006002098 W IB 2006002098W WO 2007017720 A1 WO2007017720 A1 WO 2007017720A1
Authority
WO
WIPO (PCT)
Prior art keywords
acitretin
substantially pure
solvent
salt
mixtures
Prior art date
Application number
PCT/IB2006/002098
Other languages
English (en)
Inventor
Bobba Venkata Siva Kumar
Girish Bansilal Patel
Sanjay Anantha Kale
Nitin S. Pradhan
Original Assignee
Glenmark Pharmaceuticals 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 Glenmark Pharmaceuticals Limited filed Critical Glenmark Pharmaceuticals Limited
Publication of WO2007017720A1 publication Critical patent/WO2007017720A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
    • C07C59/40—Unsaturated compounds
    • C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
    • C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/02—Preparation of carboxylic acids or their salts, halides or anhydrides from salts of carboxylic acids

Definitions

  • the present invention generally relates to a process for the preparation of substantially pure acitretin.
  • 3,7-dimethyl-2,4,6,8-nonatetraenoic acid can be represented by the structure of Formula I.
  • Acitretin an aromatic analogue of retinoic acid
  • retinol vitamin A
  • the tetraene side chain in acitretin exists in all-trans (or E) configuration.
  • Acitretin is indicated for the treatment of severe psoriasis in adults and is marketed under the trade name Soriatane ® . See, e.g., The Merck Index, Thirteenth Edition, 2001, p. 110, monograph 114; and Physician's Desk Reference, "Soriatane,” 60th Edition, pp. 1028-1035 (2005).
  • U.S. Patent No. 4,105,681 discloses processes for the preparation of acitretin.
  • Each of the processes in the '681 patent employ a Wittig reaction or its modification such as a Wittig-Horner procedure and provides a mixture of stereoisomers.
  • Attempts at preparing acitretin of the desired purity by following the processes taught in Examples 1-3 of the '681 patent were unsuccessful. See, e.g., U.S. Patent Application Publication No. 2004/0192949.
  • a similar Wittig process has been illustrated in Example 6 of DE 2636879 which provided only 47% of the all trans-isomer along with 51% of the 11-cis isomer, as an impurity.
  • U.S. Patent Application Publication No. 2004/0192949 further discloses the purification of acitretin by contacting crude acitretin with one or more solvent, optionally in the presence of a free radical scavenger, and isolating substantially pure acitretin from a mixture thereof.
  • a drawback associated with this process is it is commercially not suitable because of the instability of acitretin in most of the solvents.
  • a lithium salt of acitretin is provided.
  • the process of the present invention overcomes the problems associated with the prior art and provides a practical process for the preparation of substantially pure acitretin from a complex mixture of cis-trans isomers involving solvent treatment.
  • the process of the present invention also advantageously avoids the tedious and cumbersome purification process pf column chromatography and has benefits with respect to economics and convenience to operate on a commercial scale.
  • the present invention is directed to a process for the preparation of substantially pure acitretin of Formula I.
  • the process of the present invention includes at least (a) contacting a salt of crude acitretin with one or more solvents; and (b) isolating substantially pure acitretin from the product of step (a).
  • a salt of crude acitretin is contacted with one or more solvents to provide a substantially pure salt of acitretin.
  • Useful salts of acitretin include, but are not limited to, sodium, lithium, magnesium, potassium, strontium, magnesium, barium, calcium and the like.
  • the term "crude acitretin” as used herein shall be understood to mean acitretin containing a mixture of various cis-trans isomers as impurities. Crude acitretin is well known and may be obtained by any of the synthetic routes described in the prior art.
  • Suitable solvents for use in step (a) include, but are not limited to, ketones, alcohols, cyclic ethers, aliphatic ethers, nitriles, esters, water, alkanes, and the like and mixtures thereof.
  • Useful ketones include, but are not limited to, acetone, methyl isobutyl ketone, and the like and mixtures thereof.
  • Useful alcohols include, but are not limited to, methanol, ethanol, isopropanol, and the like and mixtures thereof.
  • Useful cyclic ethers include, but are not limited to, tetrahydrofuran, dioxane, and the like and mixtures thereof.
  • Useful nitriles include, but are not limited to, acetonitrile and the like and mixtures thereof.
  • Useful esters include, but are not limited to, ethyl acetate, and the like and mixtures thereof.
  • Useful alkanes include, but are not limited to, n-hexane, heptane and the like and mixtures thereof.
  • substantially pure salt of crude acitretin can precipitate out of the solution and then optionally recovered by, for example, filtration.
  • substantially pure salt of acitretin shall be understood to mean a salt of acitretin having an assay of greater than or equal to about 98% as determined by high performance liquid chromatography (HPLC).
  • the product substantially pure acitretin can be isolated from the substantially pure salt of acitretin by, for example, acidifying, cooling, filtering, or a combination thereof.
  • substantially pure acitretin shall be understood to mean acitretin having an assay of greater than or equal to about 98% as determined by HPLC and preferably greater than or equal to about 99%.
  • Step I Process for Salt Preparation and Purification.
  • Step II Process for Isolation of Acitretin
  • step I The substantially pure sodium salt of acitretin obtained in step I was added in water (80 ml) and acidified with 30% HCl and stirred for 30 minutes at 25 to 3O 0 C to obtain a suspension. The suspension was then filtered, washed with water and dried at 25- 3O 0 C to obtain substantially pure acitretin (7 g, assay 99.45% as determined by HPLC).
  • Step I Process for Salt Preparation and Purification

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

L'invention concerne un processus destiné à la préparation d'acitrétine sensiblement pure correspondant à la formule (I), qui consiste en ce qui suit: (a) mettre en contact un sel d'acitrétine avec un ou plusieurs solvants; et (b) isoler l'acitrétine sensiblement pure du produit au stade (a).
PCT/IB2006/002098 2005-08-05 2006-08-02 Processus destine a la preparation d'acitretine WO2007017720A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN914MU2005 2005-08-05
IN914/MUM/2005 2005-08-05
US71673405P 2005-09-13 2005-09-13
US60/716,734 2005-09-13

Publications (1)

Publication Number Publication Date
WO2007017720A1 true WO2007017720A1 (fr) 2007-02-15

Family

ID=37497037

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2006/002098 WO2007017720A1 (fr) 2005-08-05 2006-08-02 Processus destine a la preparation d'acitretine

Country Status (1)

Country Link
WO (1) WO2007017720A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2067764A1 (fr) 2007-11-07 2009-06-10 SOLMAG S.p.A. Processus de préparation d'acitrétine pur

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4105681A (en) * 1975-08-01 1978-08-08 Hoffmann-La Roche Inc. 9-phenyl 5,6-dimethyl-nona-2,4,6,8-tetraeonic acid compounds
WO2003007871A2 (fr) * 2001-07-19 2003-01-30 Ranbaxy Laboratories Limited Procede servant a preparer acitretine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4105681A (en) * 1975-08-01 1978-08-08 Hoffmann-La Roche Inc. 9-phenyl 5,6-dimethyl-nona-2,4,6,8-tetraeonic acid compounds
WO2003007871A2 (fr) * 2001-07-19 2003-01-30 Ranbaxy Laboratories Limited Procede servant a preparer acitretine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; PAN, MINGXIN ET AL: "Method for purifying Acitretin A", XP002412846, retrieved from STN Database accession no. 2006:1112693 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2067764A1 (fr) 2007-11-07 2009-06-10 SOLMAG S.p.A. Processus de préparation d'acitrétine pur

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