Process for the preparation of pyrazole carboxylic acid amides
View Patent ↗The invention relates to a process for the preparation of formula (I) which process comprises a) reacting a compound of formula (II), wherein X is chloro or bromo, with an organometallic species to (III), wherein X is chloro or bromo; reacting the halobenzyne with a fulvene (IV), to a compound of formula (V) wherein X is chloro or bromo; b) hydrogenating V in the presence of a suitable metal catalyst to a compound of formula (VI) wherein X is chloro or bromo; and either c1) reacting the compound of formula VI with NH3 in the presence of a catalyst comprising palladium and at least one ligand to the compound of formula (VII); and d) reacting the compound of formula VII in the presence of a base with a compound of formula (VIII), to the compound of formula I; or c2 reacting the compound of formula (VI) in the presence of a copper catalyst and a ligand with the compound of formula (VIIIa), to the compound of formula (I).
1. A process for the preparation of the compound of formula I
which process comprises
a) reacting a compound of formula II
wherein X is chloro or bromo, with an organometallic species in an inert atmosphere to a halobenzyne of formula III
wherein X is chloro or bromo; reacting the halobenzyne of formula III so formed with a fulvene of formula IV
to a compound of formula V
wherein X is chloro or bromo;
b) hydrogenating the compound of formula V in the presence of a suitable metal catalyst to a compound of formula VI
wherein X is chloro or bromo; and either
c1) reacting the compound of formula VI with NH 3 in the presence of a catalyst comprising palladium and at least one ligand to the compound of formula VII
and d) reacting the compound of formula VII in the presence of a base with a compound of formula VIII
to the compound of formula I; or
c2) reacting the compound of formula VI
wherein X is chloro or bromo; in the presence of a solvent, a base, a copper catalyst and at least one ligand with the compound of formula VIIIa
to the compound of formula I.
2. A process according to claim 1 , wherein in step a) the organometallic species is selected from C 1-6 alkyl- or phenyllithium halides and C 1-6 alkyl- or phenylmagnesium halides.
3. A process according to claim 1 , wherein in step c) the ligand is selected from ferrocenyl-biphosphane ligands.
4. A process according to claim 1 , which comprises reacting the compound of formula VI with NH 3 in the presence of a catalyst comprising palladium and at least one ligand to the compound of formula VIII
and reacting the compound of formula VII in the presence of a base with a compound of formula VIII
to the compound of formula I.
5. The compound of formula V
wherein X is chloro or bromo.