Expanding Synthesizable Space of Disubstituted 1,2,4-Oxadiazoles

  • ACS Comb Sci. 2016 Oct 10;18(10):616-624. doi: 10.1021/acscombsci.6b00103.
Andrey Tolmachev  1  2 ,  Andrey V Bogolubsky  1 ,  Sergey E Pipko  2  3 ,  Alexander V Grishchenko  1 ,  Dmytro V Ushakov  1 ,  Anton V Zhemera  1 ,  Oleksandr O Viniychuk  3 ,  Anzhelika I Konovets  1  4 ,  Olga A Zaporozhets  5 ,  Pavel K Mykhailiuk  1  5 ,  Yurii S Moroz  2
Affiliations
  • 1. Enamine Ltd. , 78 Chervonotkatska Street, Kyiv, 02094, Ukraine.
  • 2. ChemBioCenter, Kyiv National Taras Shevchenko University , 61 Chervonotkatska Street, Kyiv, 02094, Ukraine.
  • 3. UkrOrgSyntez Ltd. (UORSY) , 29 Schorsa Street, Kyiv, 01133, Ukraine.
  • 4. The Institute of High Technologies, Kyiv National Taras Shevchenko University , 4 Glushkov Street, Building 5, Kyiv, 03187, Ukraine.
  • 5. Department of Chemistry, Kyiv National Taras Shevchenko University , 64 Volodymyrska Street, Kyiv, 01601, Ukraine.
PMID: 27548754 DOI: 10.1021/acscombsci.6b00103
Abstract

One-pot synthesis of 3,5-disubstituted 1,2,4-oxadiazoles from carboxylic acids and nitriles was optimized to parallel chemistry. The method was validated on a 141 member library; the desired products were recovered with a high success rate and in moderate yields. Practical application of the approach was demonstrated in the synthesis of bioactive compound pifexole and agonists of Free Fatty Acid Receptor 1. A library of 4 948 100 synthesizable drug-like 3,5-disubstituted 1,2,4-oxadiazoles was enumerated based on the method and available validated reagents.

Keywords
1,2,4-oxadiazoles; carboxylic acids; nitriles; one-pot parallel synthesis; readily accessible (REAL) arrays.
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