Copper-catalysed ligation of azides and acetylenes

• US 9,040,716 B2
• Filed: 10/07/2014
• Issued: 05/26/2015
• 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:
  US14/508,552
• Publication Number:
  US 20150031895A1
• Time in Patent Office: 231 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 in human blood plasma 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, Cu(II) ion in the presence of a reducing agent, or copper metal.

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 and a ligand for Cu(I) to form a 1,4-disubstituted 1,2,3-triazole, wherein the solution comprises at least one solvent selected from the group consisting of water, a nitrile, and an alcohol.

2. The process of claim 1, wherein the solvent comprises one or more of acetonitrile, ethanol, and tert-butanol.

3. The process of claim 2, wherein the solvent further comprises water.

4. The process of claim 1, wherein the solvent comprises water and an alcohol.

5. The process of claim 1, wherein the solvent comprises water and a nitrile.

6. The process of claim 1, 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.

7. The process of claim 1, wherein the ligand is a polyvalent ligand.

8. The process of claim 1, wherein the source of catalytic Cu(I) ion comprises a Cu(I) salt.

9. The process of claim 1, wherein the source of catalytic Cu(I) ion comprises Cu(II) and a reducing agent for reducing Cu(II) to Cu(I).

10. The process of claim 9, wherein the reducing agent comprises one or more material selected from ascorbate, hydroquinone, glutathione, and cysteine.

11. The process of claim 1, wherein the source of catalytic Cu(I) comprises copper metal.

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

contacting an aqueous 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 catalytic Cu(I) ion comprises Cu(II) ion subjected to a reducing electrochemical potential sufficient to generate Cu(I) ion therefrom.

13. The process of claim 12, wherein the aqueous solution further comprises a cosolvent selected from a nitrile and an alcohol.

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

15. A two-step process for derivatizing an amine-containing molecule with a triazole comprising the steps of:

derivatizing an amino group of an amine-containing molecule with a terminal alkyne moiety to form an amino-substituted terminal alkyne; and

contacting a solution of the amino-substituted terminal alkyne with an organic azide in the presence of a source of catalytic Cu(I) ion to form a 1,4-disubstituted 1,2,3-triazole derivative therefrom.

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

17. The process of claim 16, wherein the solvent comprises one or more of acetonitrile, ethanol, and tert-butanol.

18. The process of claim 15, wherein the source of catalytic Cu(I) ion comprises a Cu(I) salt.

19. The process of claim 15, wherein the source of catalytic Cu(I) ion comprises Cu(II) and a reducing agent for reducing Cu(II) to Cu(I).

20. The process of claim 19, wherein the reducing agent comprises one or more material selected from ascorbate, hydroquinone, glutathione, and cysteine.