Enantioselective process for the preparation of both...

C - Chemistry – Metallurgy – 07 – D

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C07D 223/24 (2006.01) A61K 31/55 (2006.01) A61P 25/08 (2006.01) C07F 15/00 (2006.01)

Patent

CA 2501237

The invention relates to a novel process for the manufacture of substituted enantiopure 10hydroxy-~dihydrodibenz[b,f]azepines (la), (lb) wherein each of R1 and R2, independently, are hydrogen, halogen, amino or nitro; and each of R3 and R4, independently, are hydrogen or C1-C6alkyl; by transfer hydrogenation of 10-oxo-dihydrodibenz[b,f]azepines; and to novel catalysts of formula (III'a) and (III'b) wherein M is Ru, Rh, Ir, Fe, Co or Ni; L1 is hydrogen; L2 represents an aryl or aryl-aliphatic residue; and the further radicals have the meanings as defined herein; and to new crystal forms of both enantiomers of 10,11-dihydro-10 hydroxy-5Hdibenz[b,f]azepine-5-carboxamide, obtainable by the new processes, their usage in the production of pharmaceutical preparations, new pharmaceutical preparations comprising these new crystal forms and/or the use of these new crystal forms in the treatment of disorders such as epilepsy, or in the production of pharmaceutical formulations which are suitable for this treatment.

L'invention concerne un nouveau procédé de fabrication de 10-hydroxy-dihydrodibenz[b,f]azépines substituées enantiopures (la), (lb) où R?1¿ et R?2¿ représentent individuellement un groupe hydrogène, halogène, amino ou nitro; et R?3¿ et R?4¿ désignent individuellement un groupe hydrogène ou un alkyle en C¿1?-C¿6?; par hydrogénation de transfert de 10-oxo-dihydrodibenz[b,f]azépines; des nouveaux catalyseurs de formules (III'a) et (III'b) dans lesquelles M représente Ru, Rh, Ir, Fe, Co ou Ni; L¿1? désigne un hydrogène; L¿2? représente un groupe aryle ou un résidu d'aryle aliphatique; et les autres radicaux ont la signification présentée dans la description; ainsi que des nouvelles formes cristallines des enantiomères de 10,11-dihydro-10 hydroxy-5Hdibenz[b,f]azépine-5-carboxamide, pouvant être obtenus au moyen des nouveaux procédés, l'utilisation de ceux-ci dans la production de préparations pharmaceutiques, des nouvelles préparations pharmaceutiques renfermant ces nouvelles formes cristallines et/ou l'utilisation de ces nouvelles formes cristallines dans le traitement de troubles, tels que l'épilepsie, ou dans la fabrication de préparations pharmaceutiques conçues pour ce traitement.

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