Novel and facile process for the preparation of Brexpiprazole an antipsychotic drug

A novel and industrially viable process was developed to synthesize Brexpiprazole an antipsychotic drug. This process involves using 1,4-butanediol as a key starting material, which is then diprotected and subsequently reacted with 7-hydroxy-2(1H)-quinolinone and piperazine-l-benzo[b]thien-4-y1 hydrochloride using potassium carbonate as a base, resulting in a novel intermediate, the spiro-tosyl salt, with a good yield and purity. Various conditions, solvents and bases were evaluated to optimize the coupling reaction of tosyl salt with 7-Hydroxy-2-(1H)-Quinolinone. Finally, we have chosen Sodium carbonate as a base and selected N,N-dimethylacetamide as a solvent. The reaction was carried at an elevated temperature, resulting in the production of Brexpiprazole with good yield and excellent purity. The product is fully characterized by using analytical methods like ¹H NMR, ¹³C NMR, HPLC and HRMS analysis.