Syntheses of Pyrazolo [1, 2-a] pyrazole and Pyrazolo [5, 1-b] [1, 3] oxazine Derivatives

As a part of our search for new potent analgesic agents, novel fused pyrazole derivatives were synthesized. The reaction of 2-substituted-5-hydroxypyrazole (I) with ethyl 2-substituted (for example COCH3 or CO2C2H5) acylacetates (II) gave mainly pyrazolo [1, 2-a] pyrazole-1, 5 (1H, 5H)-diones (III). On the other hand, similar reaction of I with diethyl benzoylmalonate gave mainly pyrazolo [5, 1-b] [1, 3] oxazin-5 (5H)-one (V) but did not give III at all. Thermal and photochemical isomerization of III gave V. Methanolysis of IIIa in the presence of LiOH occurred with retention of the 4-ethoxycarbonyl-5-pyrazolone ring and similar products (VIa and VIf) were obtained by methanolysis of Va and Vf, respectively. Analgesic activities of the present new compounds were all inferior to that of aminopyrine.