Process for the preparation of a leukotriene antagonist and...

C - Chemistry – Metallurgy – 07 – D

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C07D 215/18 (2006.01)

Patent

CA 2627098

It comprises a preparation process of Montelukast from an intermediate compound of formula (Vl), which is previously prepared by reaction of the corresponding sulfonate with i-fmercaptomethyljcyclopropyljmethanol. Compound (Vl) is reacted with a Grignard reactant to convert the ester group into a tertiary alcohol, followed by conversion of the primary alcohol into a sulfonate, substitution of the sulfonate group by a cyano group, and finally transforming the cyano compound to the carboxilic acid compound by a hydrolysis reaction to afford Montelukast. Montelukast can also be prepared by a hydrolysis reaction of the corresponding amide. It also comprises intermediate compounds useful in such preparation process.

L'invention concerne un procédé de préparation de montélukast à partir d'un nouvel intermédiaire de formule (VI) préalablement préparé par mise en réaction du sulfonate correspondant avec du 1-(mercaptométhyl)cyclopropyl)méthanol. Ce procédé consiste à faire réagir le composé (VI) avec un réactif de Grignard pour convertir le groupe ester en un alcool tertiaire, à convertir l'alcool primaire en sulfonate, à substituer le groupe sulfonate par un groupe cyano puis à transformer le composé cyano en composé d'acide carboxylique par une réaction d'hydrolyse pour obtenir le montélukast. Le montélukast peut être également préparé par une réaction d'hydrolyse de l'amide correspondant. Cette invention se rapporte également à de nouveaux intermédiaires utiles dans ledit procédé de préparation.

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