Copper-catalysed ligation of azides and acetylenes

• US 8,129,542 B2
• Filed: 07/26/2010
• Issued: 03/06/2012
• Est. Priority Date: 05/30/2002
• Status: Expired due to Term

• Current Assignee: Tetard, Inc.
• Original Assignee: The Scripps Research Institute
• Inventors: Sharpless, K. Barry, Fokin, Valery, Rostovtsev, Vsevold V., Green, Luke, Himo, Fahmi
• Primary Examiner(s): POWERS, FIONA
• Application Number:
  US12/804,644
• Publication Number:
  US 20110105764A1
• Time in Patent Office: 589 Days
• Field of Search: None
• US Class Current: 548/255
• CPC Class Codes: B01J 2231/327 Dipolar cycloadditions
• CPC Class Codes: B01J 2531/16 Copper
• CPC Class Codes: B01J 2531/96 Water
• CPC Class Codes: B01J 31/1805 the ligands containing nitrogen
• CPC Class Codes: C07D 249/04 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
• CPC Class Codes: C07D 249/06 with aryl radicals directly attached to ring atoms
• CPC Class Codes: C07D 403/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

A copper catalyzed click chemistry ligation process is employed to bind azides and terminal acetylenes to provide 1,4-disubstituted 1,2,3-triazole triazoles. The process comprises contacting an organic azide and a terminal alkyne with a source of reactive Cu(I) ion for a time sufficient to form by cycloaddition a 1,4-disubstituted 1,2,3-triazole. The source of reactive Cu(I) ion can be, for example, a Cu(I) salt or copper metal. The process is preferably carried out in a solvent, such as an aqueous alcohol. Optionally, the process can be performed in a solvent that comprises a ligand for Cu(I) and an amine.

Claims

1. A copper catalyzed process for preparing a 1,4-disubstituted 1,2,3-triazole comprising:

contacting an organic azide and a terminal alkyne with Cu(I) ion in the presence of a ligand for Cu(I) to form a 1,4-disubstituted 1,2,3-triazole compound;

wherein the ligand for Cu(I) is selected from the group consisting of a nitrile, an alcohol, and a combination thereof.

2. The process of claim 1 wherein the ligand for Cu(I) comprises an alcohol.

3. The process of claim 1 wherein the ligand for Cu(I) comprises a nitrile.

4. The process of claim 3 wherein the nitrile comprises acetonitrile.

5. The process of claim 1 wherein the azide and alkyne are contacted in equimolar amounts.

6. A copper catalyzed process for preparing a 1,4-disubstituted-1,2,3-triazole comprising contacting a solution of an organic azide and a terminal alkyne with Cu(I) ion in the presence of a ligand for Cu(I) to form a 1,4-disubstituted-1,2,3-triazole compound, wherein the ligand is selected from the group consisting of an alcohol, a nitrile and a combination thereof.

7. The process of claim 6 wherein the ligand for Cu(I) comprises an alcohol.

8. The process of claim 6 wherein the ligand for Cu(I) comprises a nitrile.

9. The process of claim 8 wherein the nitrile comprises acetonitrile.

10. The process of claim 6 wherein the azide and alkyne are contacted in equimolar amounts.

11. The process of claim 6 wherein the solution is an aqueous solution.

12. The process of claim 6 wherein the solution comprises an alcohol as a solvent.

13. The process of claim 6 wherein the solution comprises acetonitrile as a solvent.

14. A copper catalyzed process for preparing a 1,4-disubstituted-1,2,3-triazole comprising contacting a solution of an organic azide and a terminal alkyne with a catalytic amount of Cu(I) ion to form a 1,4-disubstituted-1,2,3-triazole compound;

wherein the solution also comprises a ligand for Cu(I) selected from the group consisting of a nitrile, a nitrite, an isonitrile, an amine, a carboxylate, a halide, an alcohol, a thiol, and a combination thereof.

15. The process of claim 14 wherein the solution is an aqueous solution.

16. The process of claim 14 wherein the solution comprises an alcohol as a solvent.

17. The process of claim 14 wherein the solution comprises acetonitrile as a solvent.