METHOD FOR PREPARING N-PHENYLPYRAZOL-1-CARBOXAMIDES
Patent Information
- Authority / Receiving Office
- MX · MX
- Patent Type
- Patents
- Current Assignee / Owner
- FMC IP TECH GMBH
- Filing Date
- 2021-06-02
- Publication Date
- 2026-06-12
Abstract
Claims
A method for preparing a compound of formula 1 wherein X is O or S; Z is CR7 or N; R1 is H, CH3, Cl or Br; R2 is H, Br, Cl or CN; R3 is H, C1-C4 alkyl or C4-C10 cycloalkylalkyl; R4 is Cl, Br, OCF2H, OCH2CF3; or C1-C4 alkyl optionally substituted with halogen; or C1-C4 alkyl substituted with Q; R5 is F, Cl or Br; R6 is H, FoCl; R7 is H, F, Cl or Br; and Q is a 5- or 6-membered aromatic heterocyclic ring optionally substituted with one or more substituents independently selected from the group consisting of halogen, Ci-Ce alkyl, C3Ce cycloalkyl and Ci-Ce haloalkyl; comprising: combining (1) a carboxylic acid compound of formula 2, wherein Z, R4, R5, R6, R7 and Q are as defined for the compound of formula 1; and (2) an aniline compound of formula 3, R1 C(X)NHR ncconn / i znz / B / v wherein X, R1, R2 and R3 are as defined for the compound of formula 1; (3) a sulfonyl chloride to form the compound of formula 1;where the method comprises a continuous process; and (4) optionally in the presence of a base or solvent.; 2. The method according to claim 1, wherein the sulfonyl chloride is of the formula 4 R8S(O)2CI where R8 is C1-C4 alkyl, C1-C2 haloalkyl, or phenyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, C1-C3 alkyl and nitro.
3. The method according to claim 2, wherein the sulfonyl chloride is methanesulfonyl chloride.
4. The method according to any of claims 1 to 3, wherein the carboxylic acid of formula 2 is combined with the aniline of formula 3 to form a mixture and then the mixture is combined with the sulfonyl chloride.
5. The method according to any of claims 1 to 4 further comprising a base, wherein the base is combined with the compounds of formulas 2 and 3 to form the mixture prior to combining with the sulfonyl chloride.
6. The method according to claim 5, wherein the base is a tertiary amine.
7. The method according to claim 6, wherein the base is an optionally substituted pyridine.
8. The method according to claim 7, wherein the base is selected from 2-picoline, 3-picoline, 2,6-lutidine and pyridine.
9. The method according to any of claims 1 to 8 further comprising a solvent, wherein the solvent is combined with the compounds of formulas 2 and 3 and sulfonyl chloride.
10. The method according to claim 9, wherein the solvent is acetonitrile.
11. The method according to any one of claims 1 to 10, wherein X is O; R1 is CH3; R2 is H, Cl, Br or CN; and R3 is CH3 or CH2CH3.
12. The method according to any one of claims 1 to 10, wherein X is O; R1 is CH3; R2 is Cl or CN; and R3 is CH3.
13. The method according to any one of claims 1 to 10, wherein X is O; R1 is CH3; R2 is H or Br; and R3 is CH3 or CH2CH3.
14. The method according to any one of claims 1 to 10, wherein X is O or S; R1 is Cl; R2 is Cl; and R3 is CH(CH3)2.
15. The method according to any one of claims 1 to 10, wherein X is O; R1 is H or Br; R2 is Cl; and R3 is 1-(cyclopropyl)ethyl.
16. The method according to any one of claims 1 to 10, wherein Z is N; R4 is Br, R5 is Cl; and R6 is H or Cl.
17. The method according to any one of claims 1 to 10, wherein Z is N; R3 is CH3, CH2Br or 5-(trifluoromethyl)-2H-tetrazol-2-methyl; R5 is Cl; and R6 is H.
18. The method according to any one of claims 1 to 10, wherein X is O; R1 is CH3; R2 is H, Cl, Br or CN; and R3 is CH3 or CH2CH3.
19. The method according to any one of claims 1 to 10, wherein X is O; R1 is CH3; R2 is Cl or CN; and R3 is CH3.
20. The method according to any one of claims 1 to 10, wherein X is O; R1 is CH3; R2 is H or Br; and R3 is CH3 or CH2CH3.
21. The method according to any one of claims 1 to 10, wherein X is O or S; R1 is Cl; R2 is Cl; and R3 is CH(CH3)2.
22. The method according to any one of claims 1 to 10, wherein X is O; R1 is H or Br; R2 is Cl; and R3 is 1-(cyclopropyl)ethyl.
23. The method according to any one of claims 1 to 10, wherein Z is N; R4 is Br; R5 is Cl; and R6 is H or Cl.
24. The method according to any one of claims 1 to 10, wherein Z is N; R3 is CH3, CH2Br or 5-(trifluoromethyl)-2H-tetrazol-2-methyl; R5 is Cl; and R6 is H.
25. The method according to any one of claims 1 to 10, wherein X is O; Z is N; R1 is CH3; R2 is H, Cl, Br or CN; R3 is CH3 or CH2CH3; R4 is Br; R5 is Cl; and R6 is H.
26. The method according to any one of claims 1 to 10, wherein X is O or S; Z is N; R1 is Cl; R2 is Cl; R3 is CH3 or CH(CH3)2; R4 is Br; R5 is Cl; and R6 is H or Cl.
27. The method according to claim 1, wherein a compound of formula 1 is prepared and the compound is selected from the group consisting of: 3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)carbonyl]phenyl]-1-(3-chloro-2-pyridinyl)-1 / 7-pyrazol-5-carboxamide, 3-bromo-1-(3-chloro-2-pyridinyl)- / V-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazol-5-carboxamide, 1-(3-chloro-2-pyridinyl)-N-[4-cyano-2-methyl-6-[(methylamino)carbonyl]phenyl]-1H-pyrazol-5-carboxamide, and 3-bromo-N-[2-bromo-4-chloro-64[(1-cyclopropylethyl]amino]carbon¡mphenyl]-1-(3-chloro-2-pyridin¡l)-1H ncconn / i ζηζ / Β / γ pyrazole-5-carboxamide.
28. The method according to claim 1, wherein the compound of formula 2, the compound of formula 3, the sulfonyl chloride and the optional solvent or base are continuously combined in a reaction zone; and wherein the compound of formula 1 is continuously removed in an isolation step.
29. The method according to claim 28, wherein the reaction zone comprises one or more continuous reaction vessels.
30. The method according to claim 29, wherein the reaction vessels are selected from the group consisting of continuous stirred tank reactors, plug flow reactors, and combinations thereof.
31. The method according to claim 29 or claim 30, wherein the reaction zone comprises two continuous reaction vessels in series.
32. The method according to claim 29 or claim 30, wherein the reaction zone comprises a continuous reaction vessel.
33. The method according to any of claims 29 to 32, wherein each of one or more reaction vessels in the reaction zone is operated at an independent residence time and temperature.
34. The method according to any of claims 29 to 33, wherein an average residence time for portions in each reaction vessel in the reaction zone is 2 hours or less.
35. The method according to claim 34, wherein the average residence time is 15 minutes or less.
36. The method according to any of claims 28 to 35, wherein the isolation step comprises: quenching a reaction mass comprising the compound of formula 1 obtained from the reaction zone in a quenching zone to precipitate the compound of formula 1; and separating the compound of formula 1 from the quenched reaction mass by filtration to form collected solid compound of formula 1.
37. The method according to claim 36, wherein extinguishing the reaction mass comprises continuously adding an antisolvent to the reaction mass in the extinguishing zone.
38. The method according to claim 37, wherein the antisolvent is water.
39. The method according to any of claims 36 to 38, wherein the extinguishing zone consists of one or more continuous extinguishing containers.
40. The method according to any of claims 37 to 39, wherein the antisolvent added in the extinguishing zone has a pH selected from the group consisting of a neutral pH, an acidic pH, and a basic pH.
41. The method according to any of claims 37 to 40, wherein the antisolvent added to the extinguishing zone has a pH that is the same or different in each of one or more continuous extinguishing vessels.
42. The method according to any of claims 28 to 42, wherein the isolation step produces a filtrate, and wherein the filtrate is recycled back to the reaction zone.
43. The method according to claim 42, wherein the filtrate is refined or unrefined.
44. The method according to any of claims 29 to 35, wherein each reaction vessel in the reaction zone comprises one or more independent feed streams.
45. The method according to any one of claims 1 to 44, wherein the molar ratio of the compound of formula 2 to the compound of formula 3 is from approximately 1.2:1 to approximately 1:1.
2.
46. The method according to any one of claims 1 to 45, wherein the carboxylic acid compound of formula 2, the aniline compound of formula 3 and sulfonyl chloride are combined at a temperature between approximately -70 and approximately 100 °C.