Solid-Phase Synthesis of 1,3,4-Oxadiazoles and 1,3,4-Thiadiazoles via Selective Cyclization

5 SOLID-PHASE SYNTHESIS OF 1,3,4-OXADIAZOLES AND 1,3,4-THIADIAZOLES VIA SELECTIVE CYCLIZATION 

In the five-membered ring heterocyclic compound family, 1,3,4-oxadiazoles and 1,3,4-thiadiazoles have been used as privileged scaffolds to produce substances of interest in numerous therapeutic areas. In addition, these heterocycles serve as intermediates in 

Determined on the basis of LC-MS spectrum (integration of diode array 200-400 nm traces) of isolated product. 

TABLE 10.9. 5-Amino-1-(substituted-thiocarbamoyl)-1,2,4-triazoles 10 and Their Yields  

To explore the diversity of this methodology, various amines (R R N diversity elements) were used to liberate the 1,3,4-oxadiazoles 11 and 1,3,4-thiadiazoles 12 from the functionalized sulfone-containing resin. Cleavage reactions with amines generally afforded the desired products in high yields (22 examples, 72-30% yields. Table 10.10). 

---