Copper-catalysed ligation of azides and acetylenes

• US 8,877,939 B2
• Filed: 11/12/2013
• Issued: 11/04/2014
• 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:
  US14/078,106
• Publication Number:
  US 20140066632A1
• Time in Patent Office: 357 Days
• Field of Search: 548/255
• 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 human blood plasma solution of an organic azide and a terminal alkyne with a source of catalytic Cu(I) ion to form by cycloaddition a 1,4-disubstituted 1,2,3-triazole.

2. The process of claim 1 wherein the solution further comprises at least one ligand comprising at least one functional group 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.

3. The process of claim 1 wherein the solution further comprises at least one polyvalent ligand comprising 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.

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

5. The process of claim 1 wherein the source of catalytic Cu(I) comprises Cu(II) ion in combination with a reducing agent.

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

10. The process of claim 1 wherein the cosolvent comprises an alcohol.

11. The process of claim 10 wherein the alcohol comprises ethanol or tert-butanol.

7. 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 Cu(I) ion and a ligand for Cu(I) to form a 1,4-disubstituted 1,2,3-triazole, wherein the aqueous solution comprises water and a cosolvent.

8. The process of claim 7 wherein the cosolvent comprises a nitrile.

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

12. The process of claim 7 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.

13. The process of claim 7 wherein the source of Cu(I) ion comprises a Cu(I) salt.

14. The process of claim 7 wherein the source of catalytic Cu(I) comprises Cu(II) ion in combination with a reducing agent.

15. The process of claim 14 wherein the reducing agent comprises ascorbate.

16. The process of claim 14 wherein the Cu(II) ion is provided as a Cu(II) salt.

17. The process of claim 14 wherein the Cu(II) salt comprises CuSO₄ or a hydrate thereof.

18. The process of claim 7 wherein the source of catalytic Cu(I) comprises copper metal.

19. 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 Cu(I) ion and a ligand for Cu(I) to form a 1,4-disubstituted 1,2,3-triazole, wherein the aqueous solution comprises water and a cosolvent comprising ethanol, acetonitrile, or a combination thereof; and

the source of Cu(I) ion comprises a Cu(II) salt and ascorbate.

20. The process of claim 19 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.