Solid-Phase Synthesis of 2,4-diaminopyrimidines via Lewis acid-mediated aromatic nucleophilic substitution.
Primary amines were immobilized on (4-formyl-3,5-dimethoxyphenoxy)methylpolystyrene resin via reductive amination. Attachment of two different 4-chloro-2-methylthiopyrimidines, followed by sulfide oxidation, led to their corresponding sulfone intermediates. Aromatic nucleophilic substitution with various anilines or heteroaromatic amines in the presence of trimethyl aluminum afforded the desired 2,4-diaminopyrimidines after acidic cleavage from the resin. The synthetic methodology described herein was validated with the synthesis of a small 162-member library.
Arvanitis
Elena A
EA
3-Dimensional Pharmaceuticals Inc., 8 Clarke Drive, Cranbury, New Jersey 08512, USA.
Chadha
Naresh
N
Pottorf
Richard S
RS
Player
Mark R
MR
D000586:Amination; D000588:Amines; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D058116:Lewis Acids; D015394:Molecular Structure; D054852:Small Molecule Libraries; D060327:Solid-Phase Synthesis Techniques; D013450:Sulfones
D000588:Amines; D058116:Lewis Acids; D054852:Small Molecule Libraries; D013450:Sulfones