Title of Invention	PROCESS FOR THE CRYSTALLIZATION OF LOSARTAN POTASSIUM .,
Abstract	There is disclosed a process to prepare crystaltine form I of Losartan Potassium of Formula I Which comprises 1. Reacting Losartan Acid or Trilyl Losarton compouud of formula II. 44here 'R' represents hydrogen or tilphenylmethyl (trityl) protecting group with potassium hydroxide in an alcohol selected from the group consisting of methanol, ethanol, propanol, butanol and mixtures thereof to canyout in-situ de- protection, if any, il. concentration under reduced pressure to remove alcohol, and iii. adding an anti-solvent selected from the group consisting of acetone, ethyl acetate, acetonitrile, toluene' and mixtures thereof.

Title of Invention

PROCESS FOR THE CRYSTALLIZATION OF LOSARTAN POTASSIUM .,

Abstract

There is disclosed a process to prepare crystaltine form I of Losartan Potassium of Formula I Which comprises 1. Reacting Losartan Acid or Trilyl Losarton compouud of formula II. 44here 'R' represents hydrogen or tilphenylmethyl (trityl) protecting group with potassium hydroxide in an alcohol selected from the group consisting of methanol, ethanol, propanol, butanol and mixtures thereof to canyout in-situ de- protection, if any, il. concentration under reduced pressure to remove alcohol, and iii. adding an anti-solvent selected from the group consisting of acetone, ethyl acetate, acetonitrile, toluene' and mixtures thereof.

Full Text	Losartan with Potassium hydroxide in methanol/acetone without isolating the free Losartan add and requires no seeding. Brief statement of the Invention. According to the invention, there is provided a process for the crystal^tion of Losartan hydroxide in an alcohol, selected from the group consisting of methanol.ethanol.propanol.txjtanoi and mixtures therof and ii. c oncentration under reduced pressure to remove alcohol, and III. adding an antl-soh/ent selected from the group consisting of acetone.ethyl acetate, acetonitrile, toh^e and mixtures therof, to isolate L(»artan Potassium. In this process exactly one mole equivalent of potassium hydroxide as to the sta^ng compound is used. In this process, in silu de-protection is carried out to produce Losartan Potassium Detailed Deacription of the Invenntion This invention relates to the process to manufacture Losartan Potassium Form 1 without use of isopropanol /cydohexane solvent mixture. Typically Losartan free add Is suspended In a solvent and potassium hydroxide is added to obtain a dear solution, which is then concentrated under reduced pressure to remove most of the solvert. An anti-solvent is added to crystalize Losartan Potassium .The solvents to prepare Losartan Potassium indude methanol, ethanol, butanol but preferably the salt formation is carried out in methanol. Anti-solvent is seleded from common solvents such ethyl acetate, acetonirile. toiuence and acetone but the preferred anti-solvent is acetone. Losartan free add i triphenyimethyl proteded Losartan may be prepared using the reactions and techniques described In US Patent 5,138,069 and WO 93/10106. Altematively, 2-n-butyl-4-chloro-5-hydroxymcthyl-l-112'(2-triphenylmethyl)tetrazole-5-yl] inhenvl-4-vl\|mcthvl\|imida/olc(/Krci>i/r/i-rrw/ttv rrit)4U>sarlm\ a key inicrmcdiatc In the manufadure of Losartan is refluxed with Potassium hydroxide in an aicohd. preferably methanol, to perfonn and generate in situ Losartan. Potassium which is then isolated 1 A process to prepare crystattine form I of Losartan Potassium of Formula I. Which comprises 1. peacting Losartan ACid or Trityl Losarton compound of formula II. wen 'R' represents hydrogen or triphenylmethyt (trItyl) protecting group with potassium hydroxide in an alcohol selected from the group consisting of methanol, ethanol, propanol, butanol and mixtures thereof to canyout in-situ de- protection, if any, ii. concentration under reduced pressure to remove alcohol, and iii. adding an anti-solvent selected from the group consisting of acetone, ethyl acetate, acetonitrile, toluene' and mixlures thereof. 2. The process according to Claim 1 wherein exactly one mole equivalent of potassium hydroxide as to the starting compound is used. 3. A process according to Claim 1 wherein In- situ de-protection is canted out to produce Losartan Potassium. of Formula I herein described 4. A process for the crystallization of Fomi 1 of Losartan Potassium(substantially as herein described with reference to the Examples.

Full Text

Losartan with Potassium hydroxide in methanol/acetone without isolating the free Losartan add and requires no seeding.
Brief statement of the Invention.
According to the invention, there is provided a process for the crystal^tion of Losartan

hydroxide in an alcohol, selected from the group consisting of methanol.ethanol.propanol.txjtanoi and mixtures therof and
ii. c oncentration under reduced pressure to remove alcohol, and
III. adding an antl-soh/ent selected from the group consisting of acetone.ethyl acetate,
acetonitrile, toh^e and mixtures therof, to isolate L(»artan Potassium. In this process exactly one mole equivalent of potassium hydroxide as to the sta^ng compound is used.

In this process, in silu de-protection is carried out to produce Losartan Potassium Detailed Deacription of the Invenntion
This invention relates to the process to manufacture Losartan Potassium Form 1 without use of isopropanol /cydohexane solvent mixture. Typically Losartan free add Is suspended In a solvent and potassium hydroxide is added to obtain a dear solution, which is then concentrated under reduced pressure to remove most of the solvert. An anti-solvent is added to crystalize Losartan Potassium .The solvents to prepare Losartan Potassium indude methanol, ethanol, butanol but preferably the salt formation is carried out in methanol. Anti-solvent is seleded from common solvents such ethyl acetate, acetonirile. toiuence and acetone but the preferred anti-solvent is acetone.
Losartan free add i triphenyimethyl proteded Losartan may be prepared using the reactions and techniques described In US Patent 5,138,069 and WO 93/10106.
Altematively,
2-n-butyl-4-chloro-5-hydroxymcthyl-l-112'(2-triphenylmethyl)tetrazole-5-yl]
inhenvl-4-vl|mcthvl|imida/olc(/Krci>i/r/i-rrw/ttv rrit)4U>sarlm\ a key inicrmcdiatc

In the manufadure of Losartan is refluxed with Potassium hydroxide in an aicohd. preferably methanol, to perfonn and generate in situ Losartan. Potassium which is then isolated

1 A process to prepare crystattine form I of Losartan Potassium of Formula I.
Which comprises
1. peacting Losartan ACid or Trityl Losarton compound of formula II.

wen 'R' represents hydrogen or triphenylmethyt (trItyl) protecting group with potassium hydroxide in an alcohol selected from the group consisting of methanol, ethanol, propanol, butanol and mixtures thereof to canyout in-situ de- protection, if any,
ii. concentration under reduced pressure to remove alcohol, and
iii. adding an anti-solvent selected from the group consisting of acetone, ethyl acetate,
acetonitrile, toluene' and mixlures thereof.

2. The process according to Claim 1 wherein exactly one mole equivalent of potassium
hydroxide as to the starting compound is used.
3. A process according to Claim 1 wherein In- situ de-protection is canted out to produce
Losartan Potassium.
of Formula I herein described
4. A process for the crystallization of Fomi 1 of Losartan Potassium(substantially as herein
described with reference to the Examples.

Documents:

0403-mas-2001 abstract duplicate.pdf

0403-mas-2001 abstract.jpg

0403-mas-2001 abstract.pdf

0403-mas-2001 claims duplicate.pdf

0403-mas-2001 claims.pdf

0403-mas-2001 correspondence others.pdf

0403-mas-2001 correspondence po.pdf

0403-mas-2001 description (complete) duplicate.pdf

0403-mas-2001 description (complete).pdf

0403-mas-2001 drawings duplicate.pdf

0403-mas-2001 drawings.pdf

0403-mas-2001 form-1.pdf

0403-mas-2001 form-26.pdf

0403-mas-2001 form-3.pdf

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Patent Number

193625

Indian Patent Application Number

403/MAS/2001

PG Journal Number

20/2006

Publication Date

19-May-2006

Grant Date

06-Dec-2005

Date of Filing

18-May-2001

Name of Patentee

AUROBINDO PHARMA LTD

Applicant Address

PLOT NO.2 MAITRIVIHAR COMPLEX AMEERPET, HYDERABAD 500038

Inventors:

#	Inventor's Name	Inventor's Address
1	RAMESHANKAR	C/O AUROBINDO PHARMA LIMITED PLOT NO.2 MAITRIVIHAR COMPLEX AMEERPET, HYDERABAD 500038
2	VENAPU RAVINDER REDDY	C/O AUROBINDO PHARMA LIMITED PLOT NO.2 MAITRIVIHAR COMPLEX AMEERPET, HYDERABAD 500038
3	MEENAKSHISUNDERAM SIVAKUMARAN	C/O AUROBINDO PHARMA LIMITED PLOT NO.2 MAITRIVIHAR COMPLEX AMEERPET, HYDERABAD 500038
4	VIJAY KUMAR HANDA	C/O AUROBINDO PHARMA LIMITED PLOT NO.2 MAITRIVIHAR COMPLEX AMEERPET, HYDERABAD 500038

PCT International Classification Number

C07D233/16

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA