One-Pot Synthesis of Densely Substituted Pyrazolo[3,4‑<i>b</i>]‑4,7-dihydropyridines

We have achieved a facile synthesis of a combinatorial library of densely substituted pyrazolo­[3,4-<i>b</i>]-4,7-dihydropyridines the mimics of antigenital wart drug podophyllotoxinfrom 5-aminopyrazoles and 4-(methylthio) 4<i>H</i>-chromenes. The C(4) pyrazolyl 4<i>H</i>-chromenes, which also possess structural features of podophyllotoxin, were isolable intermediates in the two-step, one-pot condensation. The condensation took place in a one-pot, multicomponent manner when 3-oxo-3-phenylpropanenitriles, hydrazine (precursors for 5-aminopyrazoles) and 4-(methylthio)-4<i>H</i>-chromenes were heated in refluxing ethanol. The condensation, however, stops at 4<i>H</i>-chromene stage when methyl hydrazine or phenylhydrazine were employed. Our findings offer an opportunity for synthesis of a combinatorial library of podophyllotoxin mimics, thus paving the way for discovery of lead candidates for cancer treatment