Synthesis of Tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones

A series of tetrahydropyrazolo[1,5-c]pyrimidine2,7(1H,3H)-diones 3a-h as the first representatives of the so far unexplored saturated heterocyclic system have been synthesized, formally in 12 steps from methyl acrylate (4). The synthesis comprises a four-step preparation of methyl N-Cbz-5-alkylamino-3-oxopentanoates 9a-c, their three-step transformation into 5-{2-[(alkyl)(benzyloxycarbonyl)amino]ethyl}pyrazolidin-3-ones 12a-c, three-step selective alkylation of the amidic N-2 to give 2-alkyl-5{2-[(alkyl)(benzyloxycarbonyl) amino] ethyl} pyrazolidin-3-ones 16b-h, followed by hydrogenolytic Cbz-deprotection and subsequent cyclization of the intermediate 1,4-diamine with CDI to furnish the title compounds 3. Most of the synthetic steps were performed as a one-pot transformation.