Synthesis of New Isoxazolo[4,5-d]pyrimidines as Antitumor Agents

The present paper (publication) concerns the synthesis of new isoxazole[4,5-d]pyrimidine derivatives. There are only a few publications in the chemical literature that report the derivatives of the [4,5-d] isomer. Our new compounds, the derivatives of this isomer, were obtained using a new manner that differs from those reported in the aforementioned publications in that we used the tautomers of 3-arylo-4-imino-5-carbethoxy isxazole 3 and 4 as the starting compounds instead of using their 4-amino forms. Their tautomeric form proved chemically stable, and, as a result of ammonolysis, we obtained the compounds 5 and 6. The cyclization of the amides of 5 and 6 with various aldehydes yielded new derivatives, 10-19, with good yields. As a by-product, the 4-amino tautomer form in by degrees and was reacted also with aldehydes, and we isolated Schiff bases 20-25 with low yields. Some of these compounds were tested for their antitumor activity at National Cancer Institute, Bethesda, MD, USA.