Synthesis of thiazolo[4,5-d]pyrimidine derivatives based on purine via solid-phase synthesis

Jimin Moon; Hyojin Lee; Jungtae Kim; Shuanghui Hua; GeonHo Yoon; Hyeokjin Lee; Sugyeong Seo; Yoojin Joo; Heong-Seop Yim; Taeho Lee

doi:10.1039/D5OB00963D

Synthesis of thiazolo[4,5-d]pyrimidine derivatives based on purine via solid-phase synthesis†

Jimin Moon,

‡^a Hyojin Lee,

‡^a Jungtae Kim,

‡^a Shuanghui Hua,

^a GeonHo Yoon,

^a Hyeokjin Lee,

^b Sugyeong Seo,

^a Yoojin Joo,^a Heong-Seop Yim*^b and Taeho Lee

*^a

Author affiliations

* Corresponding authors

^a College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, BK21 FOUR KNU Community-Based Intelligent Novel Drug Discovery Education Unit, 80 Daehak-ro, Buk-gu, Daegu 41566, Korea
E-mail: tlee@knu.ac.kr

^b New Drug Development Center, Daegu-Kyeongbuk Medical Innovation Foundation (K-MEDI hub), 80 Cheombok-ro, Dong-gu, Daegu 41061, Republic of Korea

Abstract

Solid-phase synthesis was employed to construct a library of thiazolo[4,5-d]pyrimidine derivatives. The free amide at the 5-position of the thiazole, which was previously difficult to introduce via the Thorpe–Ziegler reaction, was successfully optimized in solid-phase synthesis using a 2,4-dimethoxy-substituted scaffold, and using iodine as a catalyst, the reaction with aldehyde successfully synthesized thiazolo-pyrimidinone derivatives. To synthesize thiazolo[4,5-d]pyrimidine derivatives, the direct amination reaction using BOP was successfully optimized. By applying the optimized conditions to solid-phase synthesis, a library of 36 derivatives was constructed, achieving average yields of 63–93% over six steps.

Organic & Biomolecular Chemistry

Synthesis of thiazolo[4,5-d]pyrimidine derivatives based on purine via solid-phase synthesis†

Abstract

Supplementary files

Transparent peer review

Article information

Download Citation

Permissions

Synthesis of thiazolo[4,5-d]pyrimidine derivatives based on purine via solid-phase synthesis

Social activity

Search articles by author

Spotlight

Advertisements