Synthesis of thieno[2,3-d]pyrimidin-2-ylmethanamine combinatorial library with four diversity points.
The parallel solution-phase synthesis of more than 230 substituted thieno[2,3-d]pyrimidin-2-ylmethanamines has been accomplished. This strategy is based on the cyclization of 2-aminothiophen-3-carboxylates with chloroacetonitrile to construct the thieno[2,3-d]pyrimidine core with two diversity points. Derivatization of the active chlorine and functionalization of C-4 position of the pyrimidine ring allow the introduction of other diversity points. The products containing ester groups at the 6-position of the thieno[2,3-d]pyrimidine were used in amide synthesis. Simple manual techniques for parallel reactions, coupled with simple purification procedures, gave highly pure final products. The scope and limitations of the approach are discussed.
Bogolubsky
Andrey V
AV
Enamine Ltd., 23 A. Matrosova Street, Kyiv, 01103, Ukraine.
Ryabukhin
Sergey V
SV
Stetsenko
Svetlana V
SV
Chupryna
Alexandr A
AA
Volochnyuk
Dmitriy M
DM
Tolmachev
Andrey A
AA
D000478:Alkylation; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry*; D002713:Chlorine / Q000737:chemistry; D020650:Combinatorial Chemistry Techniques; D016208:Databases, Factual; D006834:Hydrazines / Q000737:chemistry; D006900:Hydroxylation; D008697:Methane / Q000737:chemistry*; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000737:chemistry*
D000588:Amines; D006834:Hydrazines; D011743:Pyrimidines; D013438:Sulfhydryl Compounds; D002713:Chlorine; C030986:pyrimidine; D008697:Methane