Synthesis Of Aripiprazole,Palonosetron And Benzo[de]isoquinolone Derivatives

The thesis is divided into two parts, dealing with the development of anindustrially applicable route for the synthesis of aripiprazole, a recentlymarketed drug for the treatment of schizophrenia and the synthesis ofpalonosetron, a new antemetic drug, and a series analogousbenzo[de]isoquinolone derivatives, which are of interest as building blocksto afford focused library in lead compound screening in drug discovery.In the first part, a five-step synthetic route for aripiprazole is discussed.The efficient synthesis starts from 3-phenyl-propionic acid by a sequence ofreactions including nitration, reduction, conversion of the amino group to ahydroxyl group, alkylation and amine nucleophilic substitution in 33%overall yield. The final product was fully characterized by HPLC-MS,¹HNMR, ¹³CNMR and elemental analysis.In the second part, efficient and high-yielding synthetic route wasevaluated for the preparation of palonosetron and its analogousbenzo[de]isoquinolone derivatives by employing different substrates. Viadiimidation, catalytic hydrogenation, selective reduction, dehydration andhydrogenation, palonosetron and six new benzo[de]isoquinolone derivativeswere synthesized, which have never been reported. In this part, a newstrategy via the key intermediate monothioimide has been designed andattempted for the synthesis of the desired compounds, which resulted insome information useful to developing better method for the preparation ofthis type of molecules. The widely application of benzo[de]isoquinoloneanalogous in drug development will make the synthesized molecules ofpotential interest in further study.