Copper-catalysed ligation of azides and acetylenes

• US 9,302,997 B2
• Filed: 05/06/2015
• Issued: 04/05/2016
• 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 A., Green, Luke, Himo, Fahmi
• Primary Examiner(s): KOSACK, JOSEPH R
• Application Number:
  US14/705,527
• Publication Number:
  US 20150232432A1
• Time in Patent Office: 335 Days
• US Class Current: 1/1
• 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 a solution of an organic azide and a terminal alkyne with a source of catalytic Cu(I) ion to form a 1,4-disubstituted 1,2,3-triazole, wherein the source of Cu(I) ion comprises Cu(II) and a metal capable of reducing Cu(II) to Cu(I). In some embodiments, the metal capable of reducing Cu(II) to Cu(I) is selected from the group consisting of Al, Be, Co, Cr, Fe, Mg, Mn, Ni, and Zn.

Claims

1. 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 source of catalytic Cu(I) ion to form a 1,4-disubstituted 1,2,3-triazole, wherein the source of Cu(I) ion comprises Cu(II) and a metal capable of reducing Cu(II) to Cu(I).

2. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) is selected from the group consisting of Al, Be, Co, Cr, Fe, Mg, Mn, Ni, and Zn.

3. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) comprises Al.

4. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) comprises Be.

5. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) comprises Co.

6. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) comprises Cr.

7. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) comprises Fe.

8. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) comprises Mg.

9. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) comprises Mn.

10. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) comprises Ni.

11. The process of claim 1, wherein the metal capable of reducing Cu(II) to Cu(I) comprises Zn.

12. The process of claim 1, wherein the solution further comprises a ligand for Cu(I).

13. The process of claim 12, wherein the ligand comprises one or more functional groups selected from the group consisting of a nitrile, an isonitrile, a primary amine, a secondary amine, a tertiary amine, a nitrogen bearing heterocycle, a carboxylate, a halide, an alcohol, a thiol, a sulfide, a phosphine, and a phosphite.

14. The process of claim 12, wherein the ligand comprises a polyvalent ligand.

15. The process of claim 1, wherein the solution comprises at least one solvent selected from the group consisting of water, a nitrile, and an alcohol.

16. The process of claim 1, wherein the solution comprises at least one solvent selected from the group consisting of acetonitrile, ethanol, and tert-butanol.

17. The process of claim 1, wherein the solution is an aqueous solution.