Solid-phase synthesis of 2,4,6-triaminopyrimidines

Substituted pyrimidines are an important class of kinase inhibitors. We the refore developed a synthetic route suitable for the solid-phase synthesis o f 2,4,6-triaminopyrimidines through displacement reactions on deactivated p yrimidines. Functionalising the pyrimidines was achieved using a range of p rimary and secondary amines and aniline and was realised on polystyrene res in with temperatures up to 140 degrees C. Two different amination reactions were performed following the anchoring of 4,6-dichloro-2-thiomethyl-pyrimi dine (4) onto Rink-amide derivatised resin. The regio- and chemoselectivity for the displacement was studied for different leaving groups. The most co nsistent results were obtained when chlorine was used in 6-position and a m ethylsulfonyl group in the 2-position. A small library of substituted pyrim idines was prepared to ascertain the extent of the developed chemistry.