Preparation of a 7-Arylthieno[3,2-d]pyrimidin-4-Amine Library

Abstract

A focused kinase library of 7-arylthieno[3,2-d]pyrimidin-4-amine analogues is readily prepared via solution-phase parallel synthesis. This strategy relies on a key cyclization of a 3-aminothiophene-2-carboxamide with a formamide to construct the thienopyrimidine core. Further elaborations of this core via substitution and Suzuki coupling reactions allow the introduction of other diversity points. This methodology is demonstrated through the preparation of a 72-membered library of 7-arylthieno[3,2-d]pyrimidin-4-amines in good yields and high purities.

One‐pot Synthesis of 2,4‐Diamino‐substituted Thieno[3,2‐d]pyrimidines

“…Traditionally 2,4-disubstitued thieno-[3,2-d]pyrimidines were prepared in a stepwise way. 4 In our previous work, we have reported that the two chlorine atoms in 2-and 4-position showed different reactivity and chloride at 4-position can be removed under mild hydrogenation condition in the presence of NaHCO 3 . 5 Considering this reactivity difference of the two chlorine atoms, we propose that various organic amines will attack these two chlorine atoms sequentially, therefore, introduction of two different amino groups in a one-pot way would be feasible.…”

Novel Solid‐phase and Solution‐phase Synthetic Methods for Trisubstituted Thieno[3,2‐d]pyrimidine Derivatives

“…Therefore, the thieno[3,2‐ d ]pyrimidine ring system can be regarded as a privileged structure that exhibits a broad range of biological activity across several target families, and that could yield promising libraries when appropriately modified. However, efforts to construct screening libraries based on the thieno[3,2‐ d ]pyrimidine system in a combinatorial fashion have only rarely been published . Given our continuing interest in high‐throughput chemistry for hit‐ and lead‐finding heterocyclic compound screening libraries, we decided to utilize the thieno[3,2‐ d ]pyrimidine system as a candidate scaffold and to develop high‐throughput synthetic methods for its derivatives.…”

Unexpected CO bond formation in Suzuki coupling of 4‐chlorothieno[2,3‐d]pyrimidines

“…Munchhof et al [7] reported the design and structure activity relationship (SAR) of thieno[3,2‐ d ]‐pyrimidines and ‐pyridines as selective VEGFR‐2 kinase inhibitors. Since then, many patents were filed and consequently, thienopyrimidines have become a well‐sought privileged class of compounds in drug discovery programs and practical strategies for the construction of libraries have been developed [8].…”