Process for the preparation of...

C - Chemistry – Metallurgy – 07 – D

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C07D 413/04 (2006.01) C07D 221/16 (2006.01) C07D 401/04 (2006.01) C07D 401/06 (2006.01) C07D 413/06 (2006.01) C07D 413/14 (2006.01)

Patent

CA 2465686

A process and new oxazolinic intermediates for the preparation of 4-(8-chloro- 5,6-dihydro-11H-benzo-[5,6]-ciclohepta-[1,2-b]-pyridin-11-ylidene)-1- piperidinecarboxylic acid ethyl ester (loratadine) is described. The process starts from 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-3-methyl-pyridine, a new intermediate to obtain loratadine. 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-3- methyl-pyridine is condensed with 3-chloro-benzyl-chloride and the resultant product is treated with Grignard reagent of 4-chloro-N-methyl-piperidine. [3- (2-(3-chloro-phenyl)-ethyl]-pyridin-2-yl]-1-(methyl-piperidin-4-yl)-methanone is obtained for subsequent hydrolysis. Starting from this last compound it is possible to obtain loratadine with known methods.

L'invention concerne un procédé et de nouveaux intermédiaires oxazoliniques pour la préparation d'éthylester d'acide de 4-(8-chloro-5,6-dihydro-11H-benzo-[5,6]-cyclohepta-[1,2-b]-pyridin-11-ylidène)-1-pipéridinecarboxylique (loratadine). Ce procédé part de 2-(4,4-diméthyl-4,5-dihydrooxazol-2-yl)-3-méthyl-pyridine, un nouvel intermédiaire pour obtenir de la loratadine. La 2-(4,4-diméthyl-4,5-dihydrooxazol-2-yl)-3-méthyl-pyridine est condensée avec du 3-chloro-benzyl-chlorure, et le produit obtenu est traité avec un réactif grignard de 4-chloro-N-méthyl-pipéridine. La [3-(2-(3-chloro-phényl)-éthyl]-pyridin-2-yl]-1-(méthyl-pipéridin-4-yl)-méthanone est obtenue pour une hydrolyse ultérieure. A partir de ce dernier composé, il est possible d'obtenir de la loratadine par le biais de procédés connus.

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