Copper-catalysed ligation of azides and acetylenes

• US 7,375,234 B2
• Filed: 05/30/2003
• Issued: 05/20/2008
• Est. Priority Date: 05/30/2002
• Status: Expired due to Term

• Current Assignee: Tetard, Inc.
• Original Assignee: The Scripps Research Institute
• Inventors: Green, Luke, Fokin, Valery, Sharpless, K. Barry, Himo, Fahmi, Rostovtsev, Vsevold A.
• Primary Examiner(s): POWERS, FIONA
• Application Number:
  US10/516,671
• Publication Number:
  US 20050222427A1
• Time in Patent Office: 1,817 Days
• Field of Search: 548/255, 552/4, 556/112
• 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 metal catalyzed click chemistry ligation process is employed to bind azides and terminal acetylenes to give triazoles. In many instances, the reaction sequence regiospecifically ligates azides and terminal acetylenes to give only 1,4-disubstituted [1,2,3]-triazoles.

Claims

1. A Cu(I) catalyzed process for preparing a 1,4-disubstituted 1,2,3-triazole comprising:

contacting an organic azide and a terminal alkyne with a catalytic quantity of Cu(I) ion for a time sufficient to form by cycloaddition a 1,4-disubstituted 1,2,3-triazole.

2. The process in accordance with claim 1 wherein the cycloaddition is carried out at ambient temperature.

3. The process in accordance with claim 1 wherein equimolar amounts of the organic azide and the terminal alkyne are contacted with a catalytic quantity of the Cu(I) ion.

4. The process in accordance with claim 1 wherein said catalytic quantity of the Cu(I) ion is generated in situ by reduction of Cu(II) to Cu(I) with a reducing agent.

5. The process in accordance with claim 4 wherein the reducing agent is sodium ascorbate.

6. The process in accordance with claim 4 wherein Cu(II) sulfate pentahydrate is reduced by sodium ascorbate.