Copper-catalysed ligation of azides and acetylenes
View Patent ↗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.
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.