Synthesis of an Antibacterial Compound Containing a 1,4-Substituted 1H-1,2,3-Triazole: A Scaleable Alternative to the "Click" Reaction

The copper-catalyzed "click" reaction of an azide with an alkyne has become a popular method to build tip 1,4-substituted 1H-1,2,3-triazoles in medicinal chemistry and this approach was used on a laboratory scale during the preparation of novel macrolide 1. However, the manufacture of the key azide component, as well as its subsequent use in the presence of a copper catalyst on a large scale, was associated with potential safety concerns. Therefore, a sequence was developed in which construction of the 1,4-substituted 1H-1,2,3-triazole in 1 was accomplished via cyclocondensation of an alpha,alpha-dichloro tosyl hydrazone with an amine.