Process for the synthesis of...

C - Chemistry – Metallurgy – 07 – D

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C07D 215/56 (2006.01)

Patent

CA 2521294

There is provided a process for the preparation of 3-cyano-6-alkoxy-7-nitro-4~- quinolone intermediates useful for the preparation of protein tyrosine kinase (PTK) inhibitors which are useful in the treatment of cancer of the formula, wherein R is alkyl(C,-C3) prepared by reacting a substituted anthranilate with N,N~dimethylformamide dimethyacetal to obtain a N,N-dimethylamidine which is condensed with t-butylcyanoacetate to obtain a N-(2-cyano-2- t~butoxycarbonylvinyl)anthranilate, which is hydrolyzed to yield a N-(2-cyano- 2~carboxyvinyl)anthranilate followed by decarboxylating to obtain a N-(2-cyano- 2~ carboxyvinyl)anthranilate followed by cyclizing to obtain a 3-cyano-6- alkoxy-7-nitro-4~quinolone.

L'invention concerne un procédé de préparation d'intermédiaires de 3-cyano-6-alkoxy-7-nitro-4-quinolones utilisés pour produire des inhibiteurs de la protéine tyrosine kinase (PTK) utiles pour traiter le cancer. Ces intermédiaires sont représentés par la formule (I) dans laquelle R représente (C¿1?-C¿3?) alkyle préparé par réaction d'un anthranilate substitué par N,N-dimethylformamide dimethyacetal afin d'obtenir un N,N-diméthylamidine condensé avec un t-butylcyanoacétate afin d'obtenir un N-(2-cyano-2-t-butoxycarbonylvinyl)anthranilate qui est hydrolysé afin de produire un N-(2-cyano-2-carboxyvinyl)anthranilate, puis décarboxylé afin d'obtenir un N-(2-cyano-2- carboxyvinyl)anthranilate et cyclisé afin d'obtenir un 3-cyano-6-alkoxy-7-nitro-4-quinolone.

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