Synthesis of bicyclic pyrimidine derivatives as ATP analogues.
A highly efficient and general solid-phase synthesis of bicyclic pyrimidine derivatives that target purine dependent proteins is reported. The synthesis of the key intermediate, 4,6-disubstituted-5-amino-pyrimidine, involved reduction of the corresponding nitro derivatives using 1,1'-dioctyl-viologen in a triphasic milieu. The mild reduction conditions enable the use of any acid labile solid support as well as a wide range of combinatorial substituents, thus enabling the synthesis of large libraries of highly diverse bicyclic pyrimidines. Alternative reduction conditions with tin(II) chloride and structure-reactivity studies are discussed as well.
Makara
G M
GM
NeoGenesis Drug Discovery, 840 Memorial Drive, Cambridge, Massachusetts 02139, USA. gregm@neogenesis.com
Ewing
W
W
Ma
Y
Y
Wintner
E
E
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives*; D006574:Heterocyclic Compounds, 2-Ring / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D011743:Pyrimidines / Q000138:chemical synthesis*
D006574:Heterocyclic Compounds, 2-Ring; D011743:Pyrimidines; D000255:Adenosine Triphosphate