A convenient synthesis of novel substituted isoxazolo[5,4-d]pyrimidines

In this work, we present a convenient synthetic route to novel substituted derivatives of isoxazolo[5,4-d]pyrimidines. Starting from 5-amino-isoxazole-4-carboxamides, we have obtained a series of 3,6-substituted isoxazolo[5,4-d]pyrimidin-4(5H)-ones via intermolecular cyclization of initial heterocycles with ethyl triethoxyacetate or diethyl oxalate/succinate. We have also synthesized a number of 4-amino substituted isoxazolo[5,4-d]pyrimidines and 4-amino-isoxazolo[5,4-d]pyrimidine-6-carboxamides using a convenient and simple synthetic approach. We demonstrate the usefulness and versatility of the developed strategy, which can be easily adapted to high-throughput combinatorial format, for the synthesis of variously substituted compounds containing this core fragment.