Method for the preparation of aripiprazole, and...

C - Chemistry – Metallurgy – 07 – D

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C07D 215/22 (2006.01) C07C 49/67 (2006.01) C07D 295/088 (2006.01)

Patent

CA 2584789

The invention disclosed in this application relates to an improved process for the preparation of aripiprazole (1) which comprises (i) Reacting 6-hydroxy-l- indanone (11) with 1,4-dihalobutane (12) in the presence of a base and a solvent at a temperature in the range of 90 to 110 deg C to form the novel intermediate 6-(4-halo butoxy)-indan-l-one (3), (ii) reacting the novel intermediate with 1-(2,3-clichlorophenyl)-piperazine (9) to get another novel intermediate 6-[4-[4-(2,3-dichlorophenyl)-l-piperazinyl] butoxy]-indan-l-one (2) and (iii) Reacting the resulting novel compound with sodium azide. The invention also relates to the novel intermediates of the formulae (2) & (3) and processes for their preparation.

L~invention décrite dans la présente demande concerne un procédé amélioré de préparation de l~aripiprazole (1), selon lequel : (i) on fait réagir de la 6-hydroxy-1-indanone (11) avec du 1,4-dihalobutane (12) en présence d~une base et d~un solvant, à une température allant de 90 à 110 degrés C, afin de former le nouvel intermédiaire 6-(4-halobutoxy)indan-1-one (3) ; (ii) on fait réagir le nouvel intermédiaire avec de la 1-(2,3-dichlorophényl)pipérazine (9) pour obtenir un autre nouvel intermédiaire 6-[4-[4-(2,3-dichlorophényl)-1-pipérazinyl] butoxy]indan-1-one (2) ; et (iii) on fait réagir le nouveau composé résultant avec de l~azide sodique. L~invention concerne également les nouveaux intermédiaires de formules (2) et (3) et des procédés pour les préparer.

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