Synthesis of 1-(2′-Deoxy-β-D-ribofuranosyl)-1H-imidazo[4,5-d]- pyridazine-4,7(5H,6H)-dione: A potential building block for antisense applications

Abstract

Synthesis of the title compound,1-(2′-deoxy-β-D-ribofuranosyl)- 1H-imidazo[4,5-d]pyridazine-4,7(5H,6H)-dione (1), is reported. It was synthesized in five steps, commencing with methyl 1-(β-D-ribofuranosyl) imidazo-4,5-dicarboxylate (2). The 3′,5′-hydroxyl groups of 2 were protected with a bis-silylating agent to form 3, which was then converted into the corresponding 2′-thionocarbonate derivative 5. The reduction of the latter with tri-n-butyltin hydride (to form 6), followed by silyl deprotection with tetra-n-butylammonium fluoride, afforded 7. Treatment of the latter with hydrazine hydrate yielded the target nucleoside 1.