Processes for producing cycloalkylcarboxamido-pyridine benzoic acids

• US 9,776,968 B2
• Filed: 03/17/2016
• Issued: 10/03/2017
• Est. Priority Date: 12/07/2007
• Status: Active Grant

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Siesel, David
• Primary Examiner(s): Morris, Patricia L
• Application Number:
  US15/073,591
• Publication Number:
  US 20160200712A1
• Time in Patent Office: 565 Days
• Field of Search: 546304, 546311
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/73 Unsubstituted amino or imino radicals
• CPC Class Codes: C07D 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links

Abstract

The present invention relates to a process of providing the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid in substantially free form (Compound 1).

Claims

1. A process for preparing a compound of formula 6a:

2. The process of claim 1, wherein the first organic solvent is an aprotic solvent.

3. The process of claim 1, wherein the first organic solvent is toluene.

4. The process of claim 1, wherein the first organic solvent is a protic solvent.

5. The process of claim 1, wherein the first base is an inorganic base.

6. The process of claim 1, wherein the first base is potassium carbonate.

7. The process of claim 1, wherein the transition-metal catalyst is a palladium-based catalyst.

8. The process of claim 1, wherein the palladium-based catalyst is Pd(dppf)Cl₂.

9. The process of claim 1, wherein the cross coupling reaction is run at between 60°

C. and 100°

C.

10. The process of claim 1, wherein the oxidation reaction is carried out using a peroxide.

11. The process of claim 1, wherein the oxidation reaction is carried out using peracetic acid.

12. The process of claim 1, wherein the oxidation reaction is carried out in the presence of an anhydride.

13. The process of claim 1, wherein the oxidation reaction is carried out in the presence of phthalic anhydride.

14. The process of claim 1, wherein the oxidation reaction is run at between 25°

C. and 65°

C.

15. The process of claim 1, wherein the amination reaction is carried out in the presence of a sulfonyl compound.

16. The process of claim 1, wherein the amination reaction is carried out in the presence of methanesulfonic anhydride.

17. The process of claim 1, wherein the amination reagent used in the amination reaction is an alcohol amine.

18. The process of claim 1, wherein the amination reagent used in the amination reaction is ethanolamine.