Method for preparing 2-aminobenzamide derivatives
View Patent ↗A method for preparing a compound of Formula 1 comprising contacting a compound of Formulae 2 and 3 in the presence of a palladium source, a ligand, a base and carbon monoxide wherein R 1 , R 2 , X and R 3 are as defined in the disclosure. A method for preparing a compound of Formula 5 wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and Z are as defined in the disclosure, using a compound of Formula 1 characterized by preparing a compound of Formula 1 by the method disclosed above or using a compound of Formula 1 prepared by the method above.
1. A method for preparing a compound of Formula 1
wherein
R 1 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 6 haloalkoxy;
R 2 is F, Cl or cyano; and
R 3 is H, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, C 4 -C 7 alkylcycloalkyl or cyclopropylcyclopropyl;
comprising the steps of preparing a compound of Formula 4
wherein
R 1 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 6 haloalkoxy;
R 2 is F, Cl or cyano; and
R 8 is C 1 -C 14 alkyl, C 2 -C 14 hydroxyalkyl, C 3 -C 14 dialkylaminoalkyl, or C 3 -C 14 halodialkylaminoalkyl
by contacting a compound of Formula 2
wherein
R 1 is C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, C 1 -C 4 alkoxy or C 1 -C 6 haloalkoxy;
R 2 is F, Cl or cyano;
X is Br or I;
with a compound of Formula 6
R 8 OH 6
wherein R 8 is methyl, ethyl, isopropyl, hydroxyethyl, hydroxypropyl or dimethylaminoethyl;
in the presence of a palladium source, a ligand, a base and carbon monoxide;
followed by aminating in the presence of a compound of Formula 3
R 3 NH 2 3
wherein
R 3 is H, C 1 -C 4 alkyl, C 3 -C 6 cycloalkyl, C 4 -C 7 cycloalkylalkyl, C 4 -C 7 alkylcycloalkyl or cyclopropylcyclopropyl.
2. The method of claim 1 wherein R 1 is C 1 -C 4 alkyl; and R 2 is Cl or cyano.
3. The method of claim 1 wherein R 3 is H, methyl, isopropyl or cyclopropylcyclopropyl.
4. The method of claim 1 wherein X is Br.
5. The method of claim 1 wherein R 1 is methyl; R 2 is Cl or cyano; and R 3 is methyl.
6. The method of claim 1 wherein R 8 in the compound of Formula 6 is methyl, ethyl, isopropyl, hydroxyethyl or dimethylaminoethyl.
7. The method of claim 6 wherein R 8 in the compound of Formula 6 is hydroxyethyl or dimethylaminoethyl.
8. The method of claim 1 wherein the palladium source is a palladium(II) species and the ligand is selected from 1,1′-bis(diphenylphosphino)ferrocene and 1,4-bis(diphenylphosphino)butane.
9. The method of claim 8 wherein the palladium source is palladium(II) acetate and the ligand is 1,4-bis(diphenylphosphino)butane.
10. The method of claim 1 wherein the contacting is performed in a suitable solvent comprising a mixture of ethylene glycol and N,N-dimethylethanolamine.