WO2008021346B1 - Pure paliperidone and processes for preparing thereof - Google Patents

Pure paliperidone and processes for preparing thereof

Info

Publication number
WO2008021346B1
WO2008021346B1 PCT/US2007/017956 US2007017956W WO2008021346B1 WO 2008021346 B1 WO2008021346 B1 WO 2008021346B1 US 2007017956 W US2007017956 W US 2007017956W WO 2008021346 B1 WO2008021346 B1 WO 2008021346B1
Authority
WO
WIPO (PCT)
Prior art keywords
paliperidone
solvent
total purity
group
water
Prior art date
Application number
PCT/US2007/017956
Other languages
French (fr)
Other versions
WO2008021346A3 (en
WO2008021346A2 (en
Inventor
Santiago Ini
Naama Chasid
Kobi Chen
Osnat Porter-Kleks
Original Assignee
Teva Pharma
Santiago Ini
Naama Chasid
Kobi Chen
Osnat Porter-Kleks
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 Teva Pharma, Santiago Ini, Naama Chasid, Kobi Chen, Osnat Porter-Kleks filed Critical Teva Pharma
Priority to PCT/US2007/017956 priority Critical patent/WO2008021346A2/en
Priority to EP07836794A priority patent/EP1922319A2/en
Priority to JP2008530045A priority patent/JP2008546851A/en
Publication of WO2008021346A2 publication Critical patent/WO2008021346A2/en
Publication of WO2008021346A3 publication Critical patent/WO2008021346A3/en
Publication of WO2008021346B1 publication Critical patent/WO2008021346B1/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

The present invention provides pure paliperidone as well as purification processes to obtain thereof.

Claims

AMENDED CLAIMS received by the International Bureau on 09 April 2008 (09/04/2008)What is claimed is:
1. Paliperidone having a total purity of at least about 98%.
2. Paliperidone of claim 1 having a total purity of at least about 99%.
3. Paliperidone of claim 2 having a total purity of at least about 99.9%.
4. Paliperidone of claim 1 having a total purity of about 98% to about 99.9%.
5. Paliperidone of claim 4 having a total purity of about 99% to about 99.9%.
6. Paliperidone of claim 1 having a total purity of about 98% to about 99.99%.
7. Paliperidone of claim 6 having a total purity of about 99% to about 99.99%.
8. Paliperidone of anyone of claims 1-7, comprising PLP-NO at less than about 0.2%.
9. Paliperidone of anyone of claims 1-7, comprising PLP-NO at less than about 0.1%.
10. Paliperidone of anyone of claims 1-7, comprising PLP-NO at less than about 0.02%.
11. Paliperidone of claim 8, further comprising PLP-car at less than about 0.2%.
12. Paliperidone of claim 10, further comprising PLP-car at less than about 0.02%.
13. A process for purifying paliperidone, comprising crystallizing paliperidone from at least one solvent selected from the group consisting of Cj-6 ketones, a mixture of a C3-6 ketone and water, N-methylpyrrolidone, C3-6 amides, halo- substituted C6-12 aromatic hydrocarbons, propylene glycol, dimethyl sulfoxide, di-methyl carbonate, Ci^ alkyl alcohols, a mixture of a C1^ alkyl alcohol and water, acetonitrile, a mixture of acetonitrile and water, C2-6 alkyl acetates, a mixture of a C2.6 alkyl acetate and water, cellosolve, dimethyl carbonate, polyethylene glycol methyl ether and C2-8 ethers to obtain the purified paliperidone, wherein the total purity of the purified paliperidone is higher than the total purity of the starting paliperidone.
14. The process of claim 13, wherein the Cj.β ketone(s) is selected from the group consisting of acetone, methyl ethyl ketone and methyl iso-butyl ketone; the C3-6 amides are selected from the group consisting of dimethylacetamide and dimethylformamide; the halo-substituted Cδ-iz aromatic hydrocarbons are selected from the group consisting of chlorobenzene and dichlorobenzene; the CM alkyl alcohol(s) is selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol and 2-butanol; the C2-6 alkyl acetate(s) is selected from the group consisting of ethyl acetate and isobutyl acetate; and the C2-8 ethers are selected from the group consisting of dibutyl ether and polyethylene glycol.
15. The process of claim 13, wherein the at least one solvent is a mixture of acetone and water.
16. The process of claim 13, wherein the at least one solvent is a mixture of solvents at a volume ratio of between about 1 : 1 to about 3:1.
17. The process of claim 16, wherein the at least one solvent is a mixture of acetone and water, or a mixture of ethanol and water.
18. The process of claim 17, wherein the at least one solvent is a mixture of acetone and water.
19. The process of claim 18, wherein the at least one solvent is acetone/water at a volume ratio of about 3:1.
20. The process of claim 13, wherein the crystallizing step comprises heating the at least one solvent and paliperidone to form a solution by complete dissolution, and thereafter precipitating paliperidone in the solution to obtain the purified paliperidone.
21. The process of claim 20, wherein the precipitating step is performed by cooling the solution to a temperature ranging from about 00C to about 300C.
22. The process of claim 21, wherein the cooling is to a temperature of about 25°C.
23. The process of claim 20, wherein the precipitating step is performed by solvent removal from the solution via evaporation.
24. A process for purifying paliperidone, comprising crystallizing paliperidone from a solvent, wherein the crystallizing step comprises dissolving the paliperidone in the solvent to obtain a solution; mixing the solution with an anti-solvent to form a mixture in order to induce crystallization of paliperidone as purified paliperidone, wherein the total purity of the purified paliperidone is higher than the total purity of the starting paliperidone.
25. The process of claim 24, wherein the dissolving step is performed at reflux and thereafter the solution is cooled.
26. The process of claim 25, wherein the solution is cooled to a temperature of about O0C to about 300C.
27. The process of claim 26, wherein the solution is cooled to a temperature of about 200C to about 3O0C.
28. The process of claim 27, wherein the solution is cooled to a temperature of about 250C.
29. The process of claim 24, wherein the mixture is maintained for at least about 5 minutes.
30. The process of claim 29, wherein the mixture is stirred.
31. The process of claim 24, wherein the solvent is selected from the group consisting of dichloromethane, dioxane and CM alkyl alcohols.
32. The process of claim 31, wherein the solvent is selected from the group consisting of dichloromethane, dioxane, n-propanol and butanol.
21
33.' The process of claim 24, wherein the anti -solvent is selected from the group consisting of methyl t-butyl ether (MTBE), methyl ethyl ketone (MEK), acetone, methyl iso-butyl ketone (MIBK), acetonitrile, cyclohexane, hexane, heptane, toluene, benzene, xylene and water.
34. The process of claim 33, wherein the anti-solvent is selected from the group consisting of MTBE, MEK, acetonitrile, cyclohexane, heptane, toluene and water.
35. The process of claim 34, wherein the anti-solvent is selected from the group consisting of MTBE, MEK, acetonitrile and toluene.
36. A process for purifying paliperidone, comprising slurrying paliperidone in an organic solvent to obtain purified paliperidone, wherein the total purity of the purified paliperidone is higher than the total purity of the starting paliperidone.
37. The process of claim 36, wherein the organic solvent is selected from the group consisting of C1.4 alkyl alcohols, C3-5 ketones and water.
38. The process of claim 37, wherein the organic solvent is selected from the group consisting of methanol, ethanol, isopropanol, acetone and water.
39. The process of claim 36, wherein the slurrying is performed at a temperature of about 200C to about 700C.
40. The process of claim 36 wherein the slurrying is performed for about 30 minutes to about 24 hours.
41. The process of claim 40, wherein the slurrying is performed for about 35 minutes to about 1 hour.
42. The process of any one of claims 13, 24 and 36, wherein the total purity of the purified paliperidone is at least about 98%.
22
43. The process of claim 42, wherein the total purity of the purified paliperidone is at least about 99%.
44. The process of claim 43, wherein the total purity of the purified paliperidone is at least about 99.9%.
45. Paliperidone prepared by the process of any one of claims 13-19, 24 and 31-39.
46. The paliperidone of claim 45 having total purity of at least about 98%.
47. The paliperidone of claim 46 having total purity of at least about 99%.
48. The paliperidone of claim 47 having total purity of at least about 99.9%.
23
PCT/US2007/017956 2006-08-14 2007-08-14 Pure paliperidone and processes for preparing thereof WO2008021346A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
PCT/US2007/017956 WO2008021346A2 (en) 2006-08-14 2007-08-14 Pure paliperidone and processes for preparing thereof
EP07836794A EP1922319A2 (en) 2006-08-14 2007-08-14 Pure paliperidone and processes for preparing thereof
JP2008530045A JP2008546851A (en) 2006-08-14 2007-08-14 Pure paliperidone and its production

Applications Claiming Priority (21)

Application Number Priority Date Filing Date Title
US83780406P 2006-08-14 2006-08-14
US60/837,804 2006-08-14
US92874507P 2007-05-10 2007-05-10
US92874707P 2007-05-10 2007-05-10
US60/928,747 2007-05-10
US60/928,745 2007-05-10
US93039207P 2007-05-15 2007-05-15
US60/930,392 2007-05-15
US92912607P 2007-06-14 2007-06-14
US60/929,126 2007-06-14
US95857107P 2007-07-05 2007-07-05
US60/958,571 2007-07-05
US92970307P 2007-07-10 2007-07-10
US60/929,703 2007-07-10
US93509407P 2007-07-26 2007-07-26
US93509307P 2007-07-26 2007-07-26
US60/935,093 2007-07-26
US60/935,094 2007-07-26
US96392207P 2007-08-07 2007-08-07
US60/963,922 2007-08-07
PCT/US2007/017956 WO2008021346A2 (en) 2006-08-14 2007-08-14 Pure paliperidone and processes for preparing thereof

Publications (3)

Publication Number Publication Date
WO2008021346A2 WO2008021346A2 (en) 2008-02-21
WO2008021346A3 WO2008021346A3 (en) 2008-04-10
WO2008021346B1 true WO2008021346B1 (en) 2008-06-05

Family

ID=44999994

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/017956 WO2008021346A2 (en) 2006-08-14 2007-08-14 Pure paliperidone and processes for preparing thereof

Country Status (3)

Country Link
EP (1) EP1922319A2 (en)
JP (1) JP2008546851A (en)
WO (1) WO2008021346A2 (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7820816B2 (en) 2006-08-23 2010-10-26 Teva Pharmaceutical Industries Ltd. Process for the synthesis of CMHTP and intermediates thereof
WO2009016653A1 (en) * 2007-07-31 2009-02-05 Natco Pharma Limited Stable polymorphic form of paliperidone and process for its preparation
EP2280967A2 (en) * 2008-03-27 2011-02-09 Actavis Group PTC EHF Highly pure paliperidone or a pharmaceutically acceptable salt thereof substantially free of keto impurity
ITMI20090663A1 (en) 2009-04-21 2010-10-22 Dipharma Francis Srl PROCEDURE FOR THE PURIFICATION OF PALIPERIDONE
ATE544766T1 (en) 2009-07-13 2012-02-15 Krka METHOD FOR SYNTHESIS OF PALIPERIDONE
EP2475663A2 (en) 2009-09-10 2012-07-18 Actavis Group Ptc Ehf Paliperidone or a pharmaceutically acceptable salt thereof substantially free of impurities
EP2343296A1 (en) 2009-12-01 2011-07-13 Chemo Ibérica, S.A. A process for the purification of paliperidone
WO2012042368A1 (en) 2010-09-30 2012-04-05 Aurobindo Pharma Limited Process for preparation of paliperidone
AU2012264476B2 (en) * 2011-05-30 2016-12-08 Cipla Limited Process for the preparation of paliperidone

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5158952A (en) * 1988-11-07 1992-10-27 Janssen Pharmaceutica N.V. 3-[2-[4-(6-fluoro-1,2-benzisoxozol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9 tetrahydro-9-hydroxy-2-methyl-4H-pyrido [1,2-a]pyrimidin-4-one, compositions and method of use
JPH0578366A (en) * 1991-09-18 1993-03-30 Nippon Steel Chem Co Ltd Production of high-purity pyromellitic anhydride
JP2920617B2 (en) * 1996-07-23 1999-07-19 有機合成薬品工業株式会社 Purification method of 4-hydroxypiperidine
JP3907390B2 (en) * 2000-06-27 2007-04-18 セントラル硝子株式会社 Process for producing optically active 4,4,4-trifluoro-1,3-butanediol
JP2002249487A (en) * 2001-02-22 2002-09-06 Sumitomo Chem Co Ltd 4-(tert-butoxycarbonyl)piperazine derivative, optically active acid addition salt of the same, method for producing them and optically active 1-[(substituted phenyl)phenylmethylpiperazine which uses them
JP4130177B2 (en) * 2001-07-23 2008-08-06 エーザイ・アール・アンド・ディー・マネジメント株式会社 Method for producing high purity riboflavin-5'-phosphate sodium salt

Also Published As

Publication number Publication date
WO2008021346A3 (en) 2008-04-10
EP1922319A2 (en) 2008-05-21
WO2008021346A2 (en) 2008-02-21
JP2008546851A (en) 2008-12-25

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