Process for the preparation of tetrazine derivatives

Abstract

The present invention provides a process for the preparation of a tetrazine derivative of formula (I), or a pharmaceutically acceptable salt thereof wherein Rrepresents a hydrogen atom, a straight or branched C-Calkyl group, C-Calkenyl group or C-Calkynyl group, which C-Calkyl group, C-Calkenyl group and C-Calkynyl group is unsubstituted or substituted with 1, 2 or 3 substituents selected from halogen atoms, straight or branched C-Calkoxy groups, C-Calkylthio groups, C-Calkylsulphinyl groups, C-Calkylsulphonyl groups and phenyl groups, which phenyl groups are unsubstituted or substituted with one or more substituents selected from C-Calkyl groups, C-Calkoxy groups and nitro groups; or Rrepresents a C-Ccycloalkyl group; and Rrepresents a group of formula —(C═O)NRR, wherein Rand Rare independently selected from hydrogen atoms, C-Calkyl groups, C-Calkenyl groups and C-Ccycloalkyl groups, which process comprises: i) providing a compound N of formula (III), wherein Ris as defined; R—N═C═O ii) absorbing the compound of formula (III) into a solvent to obtain a solution of the compound of formula (III); iii) adding to the thus obtained solution a compound of formula (II), to obtain a compound of formula (I), as defined above, wherein Ris as defined above; iv) decomposing any excess compound of formula (III) remaining by addition of water; and v) optionally salifying the thus obtained compound with a pharmaceutically acceptable acid, or base.