Traceless Solid-Phase Synthesis of 7-Aminothiazolo[4,5- d]pyrimidine-Based Library via Dimroth Rearrangement

J Org Chem. 2021 Sep 17;86(18):12517-12527. doi: 10.1021/acs.joc.1c00791. Epub 2021 Sep 1.

Abstract

Thiazolo[4,5-d]pyrimidine is one of the purine isosteres that possesses a variety of pharmaceutical activities and is an attractive scaffold for drug discovery. In this work, a novel protocol for the synthesis of 7-aminothiazolo[4,5,-d]pyrimidine scaffold libraries on solid support has been developed using a traceless linker. Dimroth rearrangement afforded the desired intermediate with a fused heterocyclic thiazolo[4,5,-d]pyrimidine core skeleton. To diversify the synthesized library, three types of building blocks were introduced to the resin-bound thiazolo[4,5,-d]pyrimidine through N-acylation, N-alkylation, and nucleophilic substitution with amines during cleavage from the resin. The synthesized compounds were produced in seven steps with overall yields of 11-48%. Additionally, physicochemical properties, as well as drug-likeness of the library, were calculated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Alkylation
  • Amines
  • Pyrimidines*
  • Solid-Phase Synthesis Techniques*

Substances

  • Amines
  • Pyrimidines