Solid-Phase Synthesis of Pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-diones

Abstract

We report a novel, and versatile solid-phase synthesis of pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-diones starting from the polymer-bound pyrimidine 3. The key step is based on the reaction of the support-bound pyrimidine 3 with isocyanates 4, involving formation of a carbamate intermediate, followed by a base-catalysed intramolecular ring closure, to give polymer-bound 3-monosubstituted 1H-pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-diones 5. At this stage, subsequent treatment with alkyl halides 6 lead to 1,3-disubstituted 2H-pyrimido[4,5-d]pyrimidine-2,4(1H,3H)-dione intermediates 7, which after oxidation and cleavage with various amines 8 gave 1,3-disubstituted 7-amino-2H-pyrimido]4,5-d]pyrimidine-2,4(1H,3H)-diones 9 in moderate yields and high purity.