Processes for the preparation of 2-aminomethlpyridines and the 2-cyanopyridines used in their preparation

• US 6,921,828 B2
• Filed: 08/21/2001
• Issued: 07/26/2005
• Est. Priority Date: 08/25/2000
• Status: Expired due to Term

• Current Assignee: Bayer Cropscience SA (Bayer AG)
• Original Assignee: Bayer Cropscience SA (Bayer AG)
• Inventors: Amin, Mehul Rasikchandra, Dann, Norman, Riordan, Peter Dominic, Mellor, Michael
• Primary Examiner(s): Tsang, Cecilia J.
• Assistant Examiner(s): COVINGTON, RAYMOND K
• Application Number:
  US10/362,728
• Publication Number:
  US 20040049048A1
• Time in Patent Office: 1,435 Days
• Field of Search: 546/286, 546/339, 546/337, 546/345
• US Class Current: 546/286
• CPC Class Codes: C07D 213/26 Radicals substituted by halogen atoms or nitro radicals
• CPC Class Codes: C07D 213/61 Halogen atoms or nitro radicals
• CPC Class Codes: C07D 213/84 Nitriles

Abstract

The invention relates to a process for the preparation of a compound of formula (V), according to the following scheme: wherein the various substituants are as defined in the description

Claims

1. A process for the preparation of a compound of general formula (I):

or a salt thereof,

which process comprises the catalytic hydrogenation of a compound of general formula (II);

or a salt thereof,

wherein X is halogen;

each Y, which may be the same or different, is halogen, haloalkyl, alkoxycarbonyl or alkylsulphonyl; and

n is 0 to 3, in the presence of a catalyst comprising palladium;

in a solvent and at a temperature in the range of from 0°

C. to 60°

C.

2. A process according to claim 1 in which X is chlorine.

3. A process according to claim 1 in which Y is halogen or haloalkyl.

4. A process according to claim 3 in which Y is trifluoromethyl.

5. A process according to claim 1 in which the amount of metal in the catalyst is from 0.05 to 0.7% by weight relative to the amount of the compound of formula (II).

6. A process according to claim 1 in which the amount of metal in the catalyst is from 0.05 to 0.3% by weight relative to the amount of the compound of formula (II).

7. A process according to claim 1 in which the amount of metal in the catalyst is from 0.1 to 0.2% by weight relative to the amount of the compound of formula (II).

8. A process according to claim 1 which is conducted in the presence of an alcohol solvent.

9. A process according to claim 8 wherein the alcohol solvent is methanol.

10. A process according to claim 1 which is performed at a hydrogen pressure of from 1 to 4 atmospheres.

11. A process according to claim 1 which is performed in the presence of a catalyst inhibitor.

12. A process according to claim 11 in which the catalyst inhibitor is selected from the group consisting of alkali metal bromides, alkali metal iodides, ammonium bromide, ammonium iodide, hydrogen bromide, and hydrogen iodide.

13. A process according to claim 1 in which the compound of formula (II) is 3-chloro-2-cyano-5-trifluoromethylpyridine.

14. The process of claim 1 further comprising the step of acylating compound (I) with a benzoyl compound of formula (IV):

wherein L is a leaving group;

R¹ and R² each represent the same or different halogen; and

m is 0, 1 or 2, to produce a compound of formula (V);

15. A process according to claim 1 which is performed in the presence of a strong acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, and phosphoric acid.

16. The process of claim 15 wherein the strong acid is hydrochloric acid.

17. The process of claim 14 wherein the compound of formula (V) is selected from the group consisting of:

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2,6-dichlorobenzamide,

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2,6-difluorobenzamide,

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2-chloro-6-fluorobenzamide,

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2,3-difluorobenzamide,

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]2,4,6-trifluorobenzamide, and

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2-bromo-6-chlorobenzamide.

18. A process for the preparation of a compound of the formula (I):

or a salt thereof,

which process comprises the catalytic hydrogenation of a compound of the formula (II);

or a salt thereof, in the presence of;

(A) a strong acid selected from the group consisting of hydrochloric acid, hydrobromic acid, sulphuric acid, and phosphoric acid,

(B) a catalyst comprising palladium,

(C) a catalyst inhibitor selected from the group consisting of alkali metal bromides, alkali metal iodides, ammonium bromide, ammonium iodide, hydrogen bromide, and hydrogen iodide;

in methanol and at a temperature in the range of from 0°

C. to 60°

C.

19. The process of claim 18 wherein the strong acid is hydrochloric acid.

20. The process of claim 18 further comprising the step of acylating compound (I) with a beazoyl compound of formula (IV):

wherein L is a leaving group;

R¹ and R² each represent the same or different halogen; and

m is 0, 1 or 2, to produce a compound of formula (V);

21. The process of claim 19 wherein the compound of formula (V) is selected from the group consisting of:

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2,6-dichlorobenzamide,

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2,6-difluorobenzamide,

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2-chloro-6-fluorobenzamide,

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2,3-difluorobenzamide,

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]2,4,6-trifluorobenzamide, and

N-[(3-chloro-5-trifluoromethyl-2-pyridyl)methyl]-2-bromo-6-chlorobenzamide.