Improved process for the preparation of letrozole

Details Improved process for the preparation of letrozole Improved process for the preparation of letrozole

C - Chemistry, Metallurgy

07

D

C07D 249/08 (2006.01)

Patent

CA 2608904

The invention provides a high-yield process for the preparation of letrozole having a high purity, without the need for removal of the 4-[l-(l,3,4- triazolyl)methyl] benzonitrile impurity at the intermediate stage. The invention also provides a process for the synthesis of letrozole in which formation of the impurity 4-[l-(l,3,4-triazolyl)methyl] benzonitrile during the first stage is minimized. In the process, a 4-(halomethyl)benzonitrile is reacted with a salt of lH-l,2,4-triazole, reducing the formation of the impurity. Preferably, the preparation is conducted as a one-pot process.

L'invention concerne un procédé à haut rendement de fabrication de létrozole de haute pureté, sans nécessiter l'élimination de l'impureté 4-[1-(1,3,4-triazolyl)méthyl]-benzonitrile à l'étape intermédiaire. L'invention concerne également un procédé de synthèse de létrozole selon lequel la formation de l'impureté 4-[1-(1,3,4-triazolyl)méthyl]-benzonitrile est minimisée lors de la première étape. Selon le procédé, un 4-(halogénométhyl)benzonitrile est mis en réaction avec un sel de 1H-1,2,4-triazol, ce qui réduit la formation de l'impureté. La préparation est de préférence réalisée selon un procédé monotope.

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