184764-13-4

Usage

Chemical Properties

Yellow Solid

Uses

Intermediate in the production of Montelukast metabolites

InChI:InChI=1/C28H24ClNO2/c1-19(31)26-8-3-2-6-21(26)12-16-28(32)23-7-4-5-20(17-23)9-14-25-15-11-22-10-13-24(29)18-27(22)30-25/h2-11,13-15,17-18,28,32H,12,16H2,1H3/b14-9+/t28-/m0/s1

Upstream product

• 676-58-4 methylmagnesium chloride 
• 181139-72-0 methyl-[(E)]-2-[3(S)-[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-3-hydroxypropyl] benzoate 
• 149968-11-6 methyl 2-(3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-3-oxopropyl)benzoate 

Downstream Products

• 184764-20-3 (S)-1-{3-[(E)-2-(7-Chloro-quinolin-2-yl)-vinyl]-phenyl}-3-[2-(1-hydroxy-2-methoxymethoxy-1-methyl-ethyl)-phenyl]-propan-1-ol 
• 213380-36-0 (S)-2-(3-[3-(2-(7-chloro-2-quinolinyl)-(E)-ethenyl)phenyl]-3-tert-butyldimethylsilyloxypropyl)ethanone 
• 937275-23-5 [R,E]-1-[[[1-[3-[2-(7-chloro-2-quinolinyl) ethenyl]phenyl]-3-[2-(methylcarbonyl)phenyl] propyl]thio]methyl]cyclopropane acetic acid 
• 158966-92-8 montelukast 
• 151767-02-1 Montelukast sodium 
• 1013023-56-7 (S)-(E)-1-(2-(1-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl)-1-(methanesulfonyl-oxy)propyl)phenyl)ethanone 
• 184764-27-0 (1-{(R)-1-{3-[(E)-2-(7-Chloro-quinolin-2-yl)-vinyl]-phenyl}-3-[2-(1-hydroxy-2-methoxymethoxy-1-methyl-ethyl)-phenyl]-propylsulfanylmethyl}-cyclopropyl)-acetic acid 
• 186353-01-5 Methanesulfonic acid (S)-1-{3-[(E)-2-(7-chloro-quinolin-2-yl)-vinyl]-phenyl}-3-[2-(1-hydroxy-2-methoxymethoxy-1-methyl-ethyl)-phenyl]-propyl ester 

Relevant academic research and scientific papers

Insights into the cerium chloride-catalyzed grignard addition to esters

Addition of methylmagnesium chloride to ester 1 in the presence of cerium chloride gave significantly better yields of the tertiary alcohol 2 than the reaction performed in the absence of cerium chloride. The beneficial effect of added cerium chloride is postulated to be due to suppression of the enolization of the ketone intermediate. The use of properly activated anhydrous cerium chloride which is proposed to generate a less basic, more nucleophilic species to overcome this undesired reaction was found to be critical. The activated cerium chloride was identified as the known seven-coordinate THF solvate, [CeCl(μ-Cl)2(THF)2]n. Inactive crystal forms were also identified and the key parameters for formation of the active form were delineated.

Identification, synthesis and characterization of impurities of Montelukast sodium

Montelukast sodium is a selective leukotriene receptor antagonist which inhibits cysteinyl leukotriene CysLT1 receptor. Various synthesis of Montelukast is published. During laboratory optimization and later in bulk synthesis formation of various impurities was detected. Besides, pharma Europa draft mention nine process related impurities. However, the method of preparation of most of these impurities is not available in literature. Also, different route of synthesis will have different impurity profile and those process related impurities are not covered in pharmacopeias. In this study we report the synthesis of possible process impurities, including seven impurities (A-H) mentioned in pharma Europa.

PROCESS FOR THE PREPARATION OF MONTELUKAST, AND INTERMEDIATES THEREFOR

The invention relates to processes for making montelukast and to intermediates for use in the process, in particular compounds of formulas 2-7: L=OAc, OTs, OTf5OMs; where X=Cl, Br, I.