Condensed heterotricycles: synthesis of pyrazolo[3,4-c]qumoline derivatives

Abstract

Pyrazol[3,4-c]quinoline 4a is obtained from 4-(2-riitrophenyl)pyrazole-3-carboxylate (3a) by reduction followed by thermal cyclization. 4a undergoes aminoalkylation uniquely at N(3) to form 4b-d, as shown by ^I3C NMR. Pyrazoles 3a and 3c are methylated at N(2) to 6a and 6b respectively which are re-ductively cyclized to pyrazoloquinolones 7a and 7b. The later are transformed into amino derivatives 8b-d and 8g,h via chloro compounds 8a and 8f. The.amino alkoxypyrazoloquinoline (8e) is obtained from 8a or the lactam 7a. Cyclic hydroxamic acids 7c and 7d are prepared from the nitropyrazoles 6a and 6b by using NaBH₄ and Pd - C. A second synthesis of die pyrazolo[3,4-c]quinoline ring system consists of heating mercaptoacid (8) with methyl or phenyl hydrazine when 10a or 10b is obtained. Attempts to convert the pyrazole carboxylate 13a into an isomeric pyrazoloisoquinoline system 12 via the isocyan-ate 13d resulted only in the formation of bis-urea 14.