Process Development of 5-Fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1- piperazinyl]propyl]-1H-indole Dihydrochloride

5-fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]-propyl]-1H-indole dihydrochloride (1) facilitates 5-HT neurotransmission and was an antidepressant drug candidate. The development of a safe, rugged process for the large-scale, chromatography-free preparation of this compound is described, The main areas of optimization included a Fischer indole synthesis, preparation and chlorination of a monohydroxypyrimidine, and coupling of the resultant fragments to prepare the drug substance.