Process for the preparation of pyrido[2,1-a]isoquinoline...

C - Chemistry – Metallurgy – 07 – D

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C07D 471/04 (2006.01)

Patent

CA 2662419

The invention relates to a process for the preparation of pyrido[2, 1-a] isoquinoline derivatives of the formula (I), weherein R2, R3 and R4 are as defined in the specification, comprising the steps of: a) catalytic asymmetric hydrogenation of an enamine of the formula (II), wherein R1 is lower alkyl, in the presence of a transition metal catalyst containing a chiral diphosphane ligand, b) introduction of an amino protecting group Prot and c) amidation of the ester to form an amide of formula (V), wherein R2, R3, R4 and Prot are as defined in the specification.

Cette invention concerne une méthode de préparation de dérivés de pyrido[2,1-a]isoquinoline de formule (I), dans laquelle R2, R3 et R4 sont tels que définis dans la description. La méthode comprend: a) une étape d'hydrogénation asymétrique catalytique d'une énamine de formule (II) dans laquelle R1 est alkyle inférieur, en présence d'un catalyseur de métaux de transition contenant un ligand diphosphane chiral; b) une étape d'introduction d'un groupe Prot de protection du groupe amino; et c) une étape d'amidation de l'ester pour former un amide de formule (V) dans laquelle R2, R3, R4 et Prot sont tels que définis dans la description.

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