Synthesis of trans-disubstituted pyrazolylcyclopropane building blocks

摘要

Diastereoselective synthesis of trans-disubstituted pyrazolylcyclopropane building blocks (i.e. carboxylic acids and amines) is described starting from easily available pyrazolecarbaldehydes. The key step of the synthesis was Corey-Chaikowsky cyclopropanation of the corresponding alpha,beta-unsaturated Weinreb amides. The title compounds were prepared in four or six steps and 32-60 and 17-40 % overall yields, respectively, on up to 50 g scale. The building blocks obtained are good starting points for the design of lead-like libraries; they themselves can be considered as isosteric analogs of CNS-active drug tranylcyclopropamine.