Traceless Solid-Phase Synthesis of 7-Aminothiazolo[4,5-d]pyrimidine-Based Library via Dimroth Rearrangement.
J Org Chem
; 86(18): 12517-12527, 2021 09 17.
Article
in En
| MEDLINE
| ID: mdl-34468136
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyrimidines
/
Solid-Phase Synthesis Techniques
Language:
En
Journal:
J Org Chem
Year:
2021
Document type:
Article