851755-58-3

Upstream product

• 75-64-9 tert-butylamine 
• 807638-71-7 2-[2-[3(S)-[3-[(1E)-2-(7-chloroquinoline-2-yl)ethenyl]phenyl]-3-methanesulfonyloxypropyl]phenyl]-2-propanol 
• 162515-68-6 1-(sulfanylmethyl)cyclopropaneacetic acid 
• 920739-17-9 (S)-benzenepropanol α-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-2-(1-hydroxy-1-methyl ethyl)-α-methane sulfonate 
• 158966-92-8 montelukast 

Downstream Products

• 151767-02-1 Montelukast sodium 
• 158966-92-8 montelukast 

Relevant academic research and scientific papers

PREPARATION OF MONTELUKAST

Processes for the preparation of montelukast and its salts.

METHOD FOR ISOLATION AND PURIFICATION OF MONTELUKAST

A method of isolation of Montelukast of formula I from reaction mixtures, comprising conversion of the crude sub-stance to well-crystallizing salts with primary amines in the environment of at least one organic solvent and acetonitrile, followed by re-crystallization of these salts with simultaneous removal of chemical impurities and use of the chemically pure salts of Montelukast with primary amines for direct transformation to the pharmaceutically useful amorphous form of Montelukast sodium of formula II.

Process for the Preparation of Montelukast and Its Pharmaceutically Acceptable Salts

An improved process for the preparation of Montelukast and its pharmaceutically acceptable salts comprises of reacting (S) Benzenepropanol α-[3-[2-(7-chloro2-quinolinyl)ethenyl]phenyl]-2-(1-hydroxy-1-methyl ethyl)-α-methane sulfonate compound of formula (II) with 1-(mercapto methyl)cyclo propane acetic acid or its ester or nitrile in presence of alkali or alkaline carbonates and/or alkali or alkaline earth metal alkoxide in a suitable polar aprotic solvent with or without combination of C1-C4 alcoholic solvents and then treating with organic amine in a suitable ester and/or acetone and/or aliphatic or aromatic hydrocarbon solvents, and converting the corresponding amine salt compound of montelukast into its sodium salt compound of formula (I) using sodium ion source in methanol, without converting into montelukast free acid.

Purification process of montelukast and its amine salts

It comprises a process for the purification of Montelukast, or its salts or its solvates, including any stereoisomer or mixture thereof, which comprises converting Montelukast acid or a solvate thereof, including any stereoisomer or mixtures thereof, into an amine salt selected from the group consisting of cyclohexylamine, tris-(hydroxymethyl)aminomethane, L-(+)-treo-2-amino-1-phenyl-1,3-propanediol, R-(+)-α-methylbenzylamine, and L-(+)-α-phenylglycinol salt, in the presence of an appropriate solvent. It also comprises novel salts of Montelukast, in particular, cyclohexylamine, tris-(hydroxymethyl)aminomethane, L-(+)-treo-2-amino-1-phenyl-1,3-propanediol, R-(+)-α-methylbenzylamine, and L-(+)-α-phenylglycinol salts.

IMPROVED PROCESS FOR PURE MONTELUKAST SODIUM THROUGH PURE INTERMEDIATES AS WELL AS NOVEL AMINE SALTS

The present invention provides an improved process for the preparation of highly pure montelukast sodium through highly pure diol intermediate compound of formula (2) and (1)-(mercapto methyl) cyclopropane acetic acid methyl ester compound of formula (4) or mercaptomethyl cyclopropane acetic acid compound of formula (7). The present invention also provides novel organic amine salts of montelukast.

PREPARATION OF MONTELUKAST

A process for preparing amorphous montelukast sodium comprises removing solvent from a solution comprising montelukast sodium using agitated thin film drying.

AN IMPROVED PROCESS FOR THE PREPARATION OF MONTELUKAST AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS

An improved process for the preparation of Mσntelukast and its pharmaceutically acceptable salts comprises of reacting (S) Benzenepropanol α -[3-[2-(7-chloro2-quinolinyl) ethenyl]phenyl]-2-(l-hydroxy-1-methyl ethyl)-α-methane sulfonate compound of formula (II) with l-(mercapto methyl) cyclo propane acetic acid or its ester or nitrile in presence of alkali or alkaline carbonates and/or alkali or alkaline earth metal alkoxide in a suitable polar aprotic solvent with or without combination of C1-C4 alcoholic solvents and then treating with organic amine in a suitable ester and/or acetone and/or aliphatic or aromatic hydrocarbon solvents, and converting the corresponding amine salt compound of montelukast into its sodium salt compound of formula (I) using sodium ion source in methanol, without converting into montelukast free acid.

Process for preparation of montelukast and its salts

A process for preparation of montelukast or a salt thereof is provided, the process including reacting a late intermediate compound which is 2-[1-[1-R-3-[2-(7 chloro quinolin-2-yl) vinyl [phenyl]-3-[2-methoxy carbonyl phenyl] propyl sulfonyl methyl] cyclo propyl] acetic acid or a salt thereof with methyl magnesium chloride or methyl magnesium bromide in an organic solvent. In one embodiment, the process includes reacting an earlier intermediate compound which is methyl 2-(3-R-(3-(2-(7-chloro 2-quinolinyl)-ethenyl)-3 hydroxy propyl) benzoate with methane sulfonyl chloride or toluene sulfonyl chloride to obtain a mesylated or tosylated derivative of the earlier intermediate compound; followed by a reaction of the mesylated or tosylated derivative with 1-mercapto methyl cyclopropane acetic acid in a polar solvent in a presence of a base to obtain the late intermediate compound.