Convergent Synthesis of a 5HT7/5HT2 Dual Antagonist

The development of an efficient and convergent route to 3-(4-fluorophenyl)-2-isopropyl-2,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine (1), a potent 5HT7/5HT2 dual antagonist, is described. Significant features of this route are: (a) a regioselective construction of a tetra-substituted pyrazole 6a by reacting an N-monosubstituted hydrazone 4a with an elaborated nitroolefin 5b and (b) a unique Pd-catalyzed hydrogenation method that carries out the four-step, ring-closing reductive amination sequence in a notable one-pot operation to provide 1 in excellent overall yields.