Enantioselective preparation of pharmaceutically active...

C - Chemistry – Metallurgy – 12 – P

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C12P 41/00 (2006.01) C07D 235/28 (2006.01) C07D 401/12 (2006.01) C07D 413/14 (2006.01) C07D 471/04 (2006.01) C07D 495/04 (2006.01) C12P 17/18 (2006.01)

Patent

CA 2204000

A compound of formula (II), either as a single enantiomer or in an enantiomerically enriched form, wherein Het1 is (a) or (b), and Het2 is (c) or (d), and is (e) or (f) (wherein N in the benzimidazole moiety of Het2 means that one of the carbon atoms substituted by any one of R6 to R9 optionally may be exchanged for an unsubstituted nitrogen atom; R1, R2 and R3 are the same or different and selected from hydrogen, alkyl, alkoxy optionally substituted by fluorine, alkylthio, alkoxyalkoxy, dialkylamino, piperidino, morpholino, halogen, phenylalkyl, phenylalkoxy; R4 and R4' are the same or different and selected from hydrogen, alkyl, aralkyl; R5 is hydrogen, halogen, trifluoromethyl, alkyl, alkoxy; R6-R9 are the same or different and selected from hydrogen, alkyl, alkoxy, halogen, haloalkoxy, alkylcarbonyl, alkoxycarbonyl, oxazolyl, trifluoroalkyl or adjacent groups R6-R9 may complete together with the carbon atoms to which they are attached optionally substituted ring structures; R10 is hydrogen or alkoxycarbonyloxymethyl; R11 is hydrogen or forms an alkylene chain together with R3; R12 and R13 are the same or different and selected from hydrogen, halogen or alkyl) is obtained by stereoselective bioreduction of a compound of formula (II) in racemic form.

Composé de formule (II) préparé sous forme d'énantiomère simple ou sous forme énantiomorphe enrichie dans laquelle Het¿1? désigne (a) ou (b), et Het¿2? désigne (c) ou (d) et où désigne (e) ou (f). N dans la fraction benzimidazole de Het¿2?, signifie que l'un des atomes de carbone remplacés par l'un des groups R¿6? à R¿9? peut être échangé pour un atome d'azote non remplacé; R¿1?, R¿2? et R¿3?, identiques ou différents, sont choisis parmi hydrogène, alkyle ou alcoxy, remplaçables par fluor, alkylthio, alcoxyalcoxy, dialkylamino, piperidino, morpholino, halogène, phénylalkyle ou phénylalcoxy; R¿4? et R¿4?', identiques ou différents, sont choisis parmi hydrogène, alkyle ou aralkyle; R¿5? désigne l'hydrogène, un halogène, un trifluorométhyle, un alkyle ou le radical alcoxy; R¿6? à R¿9?, identiques ou différents, sont choisis parmi hydrogène, alkyle, alcoxy, halogène, haloalcoxy, alkylcarbonyle, alcoxycarbonyle, oxazolyle ou trifluoroalkyle, ou alors des groupes adjacents R¿6? à R¿9? peuvent former des structures cycliques de substitution avec les atomes de carbone auxquels ils sont liés; R¿10? désigne l'hydrogène ou le groupe alcoxycarbonyloxyméthyle; R¿11? désigne l'hydrogène ou des formes de la chaîne alkylène avec R¿3?; R¿12? et R¿13?, identiques ou différents, sont choisis parmi hydrogène, halogène ou alkyle. Ce composé est obtenu par bioréduction stéréosélective du composé de formule (II) sous forme racémique.

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