Copper-catalysed ligation of azides and acetylenes

• US 20110105764A1
• Filed: 07/26/2010
• Published: 05/05/2011
• Est. Priority Date: 05/30/2002
• Status: Active Grant

• Current Assignee: Tetard, Inc.
• Original Assignee: The Scripps Research Institute
• Inventors: Fokin, Valery, Sharpless, K. Barry, Himo, Fahmi, Rostovtsev, Vsevold A., Green, Luke
• Granted Patent: US 8,129,542 B2
• Time in Patent Office: Days
• 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, a nitrite, an isonitrile, a primary amine, a secondary amine, a carboxylate, chloride, an alcohol, a thiol, and a combination thereof.

18. The process of claim 1 wherein the ligand for Cu(I) comprises chloride.

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

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

21. The process of claim 20 wherein the nitrile comprises acetonitrile.

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

2-17. -17. (canceled)

23. 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.

24. The process of claim 23 wherein the ligand for Cu(I) comprises a nitrile, a nitrite, an isonitrile, an amine, a carboxylate, a halide, an alcohol, a thiol, or a combination thereof.

25. The process of claim 23 wherein the ligand for Cu(I) comprises an alcohol.

26. The process of claim 23 wherein the ligand for Cu(I) comprises a nitrile.

27. The process of claim 26 wherein the nitrile comprises acetonitrile.

28. The process of claim 23 wherein the azide and alkyne are contacted in equimolar amounts.

29. The process of claim 23 wherein the solution is an aqueous solution.

30. The process of claim 23 wherein the solution comprises an alcohol as a solvent.

31. The process of claim 23 wherein the solution comprises acetonitrile as a solvent.

32. 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.

33. The process of claim 32 wherein the solution is an aqueous solution.

34. The process of claim 32 wherein the solution comprises an alcohol as a solvent.

35. The process of claim 32 wherein the solution comprises acetonitrile as a solvent.

36. The process of claim 32 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.