Synthesis and Chemistry of 5,6,7,8-Tetrahydro-4H-Pyrazolo[1,5-a] [1,4]Diazepine-2-Carboxylates.

5,6,7,8-tetrahydro-4H-pyrazolo[1,5-a] diazepine carboxylates are valuable scaffolds for drug design and medicinal chemistry. In this paper we disclose a short scalable synthesis and chemical reactivity patterns of the pyrazolo-diazepine pharmacophore. Commercial and cheaply available Methyl pyrazole 3,5-dicarboxylate was alkylated with 3-bromo-N-Boc propyl amine and the resulting derivative underwent concomitant cyclization upon deprotection of the Boc protecting group to yield the pyrazolo-diazepine skeleton. Selective reduction of the lactam was accomplished cleanly using borane and the resulting amine was pro-tected using a tert-butyloxycarbonyl protecting group. The free N-terminal of the diazepine underwent smooth Buchwald and Chan arylations among various standard chemistry applications examined on this pharmacophore.