Cyclocondensation of oxoketene dithioacetals with 3-aminopyrazoles: a facile highly regioselective general route to substituted and fused pyrazolo [a̲]pyrimidines

Abstract

Cyclocondensation of 3-aminopyrazole (1a̲) and 3-amino-5-methylthio-4-phenylpyrazole (1b̲) with α-oxoketene dithioacetals (2a̲-j̲j derived from acyclic active methylene ketones affords 5-methylthio-6,7-substituted pyrazolo[1,5-a ] pyrimidines (3a̲-j̲ ) exclusively. The reaction was found to be equally successful for the synthesis of 7-styryl,7-(4-aryl-1,3-butadienyl) and 7-(6-aryl-1,3,5-hexatrienyl)pyrazolopyrimidines (7a̲-f̲ ) from the respective enoylketene dithioacetals (6a̲-f̲ ). Similarly, the reaction of 1a̲ and 1b̲ with cyclic and benzocyclic ketene dithioacetals also afforded the angularly fused 5-methylthiopyrazolo pyrimidines regioselectively in good yields. However the oxoketene dithioacetal from cyclopentanone yielded both angularly and linearly fused regioisomers 10̲ and 11̲ respectively in nearly equal amounts. Some of the 5-methylthiopyrazolopyrimidines were dethiomethylated with Raney nickel to afford 5-unsubstituted derivatives in good yields.