Diversification of a thieno[2,3-d]pyrimidin-4-one scaffold via regioselective alkylation reactions.
The 2-aryl-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-ones and 2-aryl-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-ones have been diversified by alkylation reactions, applying benzylchlorides and N-substituted 2-chloroacetamides as alkylating agents. Under the found uniform conditions the substitution direction does not depend on the structure of the alkylating agent and gives monoalkylated products in high yields with simple workup. The alkylation of the 2,3-dihydropyrimidin-4(1H)-one derivatives proceeds onto the N1-position; however, in the case of pyrimidin-4(3H)-ones the O-alkylated products are formed selectively. An alternative strategy for the synthesis of the N1-benzyl-2,3-dihydropyrimidin-4(1H)-one derivatives is also developed. It applies the redaction of N2-substituted Gewald's amides with aromatic aldehydes and allows simple introduction of various substituents in the final molecule.
Dzhavakhishvili
Sergey G
SG
Department of Heterocyclic Compounds, SSI Institute for Single Crystals of National Academy Science of Ukraine, Kharkiv, Ukraine.
Gorobets
Nikolay Yu
NY
Shishkina
Svetlana V
SV
Shishkin
Oleg V
OV
Desenko
Sergey M
SM
Groth
Ulrich M
UM
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry*; D000478:Alkylation; D001593:Benzyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000191:economics / Q000379:methods*; D007536:Isomerism; D011744:Pyrimidinones / Q000138:chemical synthesis* / Q000737:chemistry
D000081:Acetamides; D001593:Benzyl Compounds; D011744:Pyrimidinones; C542082:thieno(2,3-d)pyrimidin-4-one; C013874:chloroacetamide; C021292:benzyl chloride