Efficient synthesis of some novel furo[3,2-<i>e</i>]pyrazolo[3,4-<i>b</i>]pyrazines and related heterocycles

<p>A series of novel 6-functionalized-5-amino-3-methyl-1-phenyl-1<i>H</i>-furo[3,2-<i>e</i>]pyrazolo[3,4-<i>b</i>]pyrazines <b>(4a–c)</b> was synthesized by the reaction of 3-methyl-6-oxo-1-phenyl-6,7-dihydro-1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyrazine-5-carbonitrile <b>(2)</b> with α-halocarbonyl compounds such as: diethyl 2-bromomalonate, phenacyl bromide and chloroacetone. Cyclocondensation of the amino benzoyl <b>4b</b> with diethyl malonate yielded the oxopyridine carboxylate derivative <b>5</b>. Also, the starting intermediate amino ester compound <b>4a</b> was allowed to react with ethanol amine to afford the hydroxyethyl caboxamide derivative <b>6</b>. Furthermore, hydrazinolysis of the amino ester <b>4a</b> afforded the corresponding amino carbohydrazide <b>7</b> which was used as a versatile precursor for synthesis of other heterocyclic compounds attached or fused to the furopyrazolopyrazine moiety. The chemical structures of the newly synthesized compounds were confirmed on the basis of elemental and spectral analyses containing FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry hoping these molecules should allow us to investigate their pharmacological activities in the future study.</p