Process for the preparation of pyrazole carboxylic acid amides
The invention relates to a process for the preparation of a compound 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) reacting the halobenzyne of formula (III) so formed with (IV) wherein R 1 and R 2 are hydrogen or C 1 -C 6 alkyl; to (V), b) hydrogenating V in the presence of a metal catalyst to (VI), c) ozonising (VI) to (VII) d) converting (VII) in the presence of a phosphane and CCI 4 or CHCI 3 to (VIII) (VIII), and either e1) reacting VIII with NH 3 in the presence of a catalyst to (IX) and f) reacting IX in the presence of a base with the compound of formula (X), to the compound of formula (I); or e2) reacting the compound of formula (VIII), in the presence of a solvent, a base, a copper catalyst and at least one ligand with (Xa), 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
wherein R 1 and R 2 are independently hydrogen or C 1 -C 6 alkyl; to a compound of formula V
wherein R 1 and R 2 are independently hydrogen or C 1 -C 6 alkyl and 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 R 1 and R 2 are independently hydrogen or C 1 -C 6 alkyl and X is chloro or bromo;
c) ozonising the compound of formula VI to a compound of formula VII
wherein X is chloro or bromo;
d) converting the compound of formula VII in the presence of a phosphane and CCl 4 or CHCl 3 to the compound of formula VIII
wherein X is chloro or bromo; and either
e1) reacting the compound of formula VIII with NH 3 in the presence of a catalyst comprising palladium and at least one ligand to the compound of formula IX
and f) reacting the compound of formula IX in the presence of a base with the compound of formula X
to the compound of formula I; or
e2) reacting the compound of formula VIII
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 Xa
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 d) the compound of formula VII is converted into the compound of formula VIII in the presence of triphenylphosphane and carbontetrachloride.
4. A process according to claim 1 , wherein in step e) the ligand is selected from ferrocenyl-biphosphane ligands.
5. A process according to claim 1 , which comprises reacting the compound of formula VIII with NH 3 in the presence of a catalyst comprising palladium and at least one ligand to the compound of formula IX
and reacting the compound of formula IX in the presence of a base with a compound of formula X
to the compound of formula I.
6. The compound of formula VIII
wherein X is chloro or bromo.