Process for making 3-substituted 2-amino-5-halobenzamides
View Patent ↗Disclosed is a method for preparing a compound of Formula 1 by contacting compound of Formula 2 with R 1 —NH 2 in the presence of a carboxylic acid and a method for preparing a compound of Formula 2 by contacting a compound of Formula 4 with phosphorus tribromide. wherein R 1 is H, C 1 -C 4 alkyl, cyclopropyl, cyclopropylmethyl or methylcyclopropyl; R 2 is CH 3 or Cl; R 3 is C 1 -C 6 alkyl or C 3 -C 6 alkenyl, each optionally substituted with up to 3 halogen and up to 1 phenyl; and X is Cl or Br. Also disclosed is a method for preparing a compound of Formula 5 wherein R 4 , R 5 , R 6 and Z are as defined in the disclosure, using a compound of Formula 1 that is characterized by preparing the compound of Formula 1 by the method above.
1. A method for preparing a compound of Formula 1
wherein R 1 is H, C 1 -C 4 alkyl, cyclopropyl, cyclopropylmethyl or methylcyclopropyl;
R 2 is CH 3 or Cl; and
X is Cl or Br;
comprising:
contacting a compound of Formula 2
with a compound of Formula 3
R 1 —NH 2 3
in the presence of a carboxylic acid, wherein said contact is in a substantially anhydrous reaction medium comprising a suitable organic solvent.
2. A method for preparing a compound of Formula 1
wherein R 1 is H, C 1 -C 4 alkyl, cyclopropyl, cyclopropylmethyl or methylcyclopropyl;
R 2 is CH 3 or Cl; and
X is Cl or Br;
comprising:
contacting a compound of Formula 2
with a compound of Formula 3
R 1 —NH 2 3
in the presence of a carboxylic acid, wherein said contact is in a reaction medium comprising ethyl acetate.
3. A method for preparing a compound of Formula 1
wherein R 1 is H, C 1 -C 4 alkyl, cyclopropyl, cyclopropylmethyl or methylcyclopropyl;
R 2 is CH 3 or Cl; and
X is Cl or Br;
comprising:
contacting a compound of Formula 2
with a compound of Formula 3
R 1 —NH 2 3
in the presence of a carboxylic acid, wherein the Compound of Formula 2 is prepared by contacting a compound of Formula 4
wherein R 3 is C 1 -C 6 alkyl or C 3 -C 6 alkenyl, each optionally substituted with up to 3 halogen and up to 1 phenyl;
with phosphorus tribromide.
4. A method for preparing the compound of Formula 2
wherein R 2 is CH 3 or Cl; and X is Cl or Br; comprising:
contacting a compound of Formula 4
wherein R 3 is C 1 -C 6 alkyl or C 3 -C 6 alkenyl, each optionally substituted with up to 3 halogen and up to 1 phenyl;
with phosphorus tribromide.
5. The method of claim 4 wherein R 2 is CH 3 , and X is Cl.
6. A compound of Formula 4
wherein R 2 is CH 3 or Cl;
R 3 is C 1 -C 6 alkyl or C 3 -C 6 alkenyl, each optionally substituted with up to 3 halogen and up to 1 phenyl; and
X is Cl or Br;
provided that when R 2 and X are each Cl, then R 3 is other than CH 3 .
7. A compound of claim 6 wherein R 2 is CH 3 and X is Cl.
8. A compound of claim 7 wherein R 3 is C 1 -C 2 alkyl.
9. A compound of claim 6 wherein R 2 is CH 3 and X is Br.
10. A compound of claim 9 wherein R 3 is C 1 -C 2 alkyl.