Construction of the 1,2,4-Triazole Ring

Click chemistry was defined as an approach for the rapid synthesis of druglike molecules using a few practical and reliable reactions. An example of a click reaction is the Huisgen 1,3-dipolar cycloaddition of alkynes to azides to form 1,4-disubsituted-1,2,3-triazoles. The reaction is efficient, mild, and requires no protecting groups and purification in many cases. The triazole is an isostere of the amide bond, however, it does not tmdergo cleavage like amides. They are also resistant to oxidation and reduction. 

The ruthenium-catalyzed cycloaddition of azides to alkynes to form 1,5-disubstituted triazoles is complimentary to the copper catalyzed route. The Cu(I)-catalyzed reaction is limited to terminal alkynes, and the Ru(II)-catalyzed reaction is active with internal alkynes. 

Aliphatic azides are limited in availability and can be prepared by the hydroazidation of deactivated olefins in the presence of a cobalt catalyst.  

Alizapride is a dopamine antagonist with less affection on the CNS (central nervous system). It has a prokinetic and an antiemetic effect that can be used in the treatment of nausea and vomiting, including a postoperative side effect. 

Two traditional methods of the synthesis of alizapride involved construction of the benztriazole and then followed by coupling with 

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