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Updated: Mar 30, 2026
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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
A Highly Efficient Diversification of 2-Amino/Amido-1,3,4-oxadiazole and 1,3,4-Thiadiazole Derivatives via
Seung-Ju Yang1, Ji-Hye Choe1, Aizhan Abdildinova1
1Innovative Drug Library Research Center, Department of Chemistry, College of Science, Dongguk University , 26, 3-ga, Pil-dong Jung-gu, Seoul 100-715, Korea.
Abstract:
A 2-amino/amido-1,3,4-oxadiazole and 1,3,4-thiadiazole library has been constructed on solid-phase organic synthesis. The key step on this solid-phase synthesis involves the preparation of polymer-bound 2-amino-1,3,4-oxadiazole and 1,3,4-thiadiazole core skeleton resin by cyclization of thiosemicarbazide with EDC·HCl and p-TsCl, respectively. The resulting core skeleton undergoes functionalization reaction with various electrophiles such as alkyl halides, and acid chlorides to generate N-alkylamino and N-acylamino-1,3,4-oxadiazole, and 1,3,4-thiadiazole resin, respectively. Finally, the 2-amino and 2-amido-1,3,4-oxadiazole and 1,3,4-thiadiazole library was then generated in good yields and high purities by cleavage of the respective resin under trifluoroacetic acid(TFA) in dichloromethane(DCM). The constructed library shows reasonable, oral bioavailability drug properties as determine by using the Lipinski's Rule and similar parameters.
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