The present work describes an improved and efficient process for the synthesis of paliperidone (1), an antipsychotropic agent. The synthesis comprises the DBU (1,8-diazabicycloundec-7-ene) catalyzed N-alkylation of 3-(2-chloroethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]-pyrimidin-4-one (5) with 6-fluoro-3-piperidin-4-yl-1,2 benzisoxazole hydrochloride (6) in methanol as the solvent and diisopropylamine as a base to yield paliperidone (1) with 85% yield and over 97% purity by HPLC. The present work also describes an industrially efficient purification process for the removal of critical process related impurities (8 and 9) in paliperidone (1). The process furnished 1 with an overall yield of about 60% and 99.85% purity.

An improved and single pot process for the preparation of Quetiapine hemifumarate (1), an antipsychotic drug, free from potential impurities is reported with an overall yield of 80%. The reported process for its preparation suffers from the drawback of producing potential impurities identified as 11-piperazin-1-yldibenzo[b,f][1,4]thiazepine (6), 2-(4-dibenzo[b,f][1,4]thiazepin-11-ylpiperazin-1-yl)ethanol (10), dimer (9), and N-methyl-N-phenyldibenzo[b,f][1,4]thiazapine-11-amine (14). Elimination of these impurities in the process is achieved by chlorination of 3 followed by in situ condensation of obtained 4 with highly pure 8 and subsequently establishing the pH based workup to obtain free base 2, which is further converted to quetiapine hemifumarate salt free from all these impurities. In this report, different aspects of process development such as scheme selection, optimization of different process parameters, identification, synthesis, origin and control of impurities, and development of an accurate analytical method during the development of a scalable process for quetiapine hemifumarate are discussed.

The present work describes an improved and highly efficient process for the synthesis of iloperidone (1), an antipsychotic agent, which is free from potential impurities. The synthesis comprises N-alkylation of 1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanone (4) with 6-fluoro-3-piperidin-4-yl-1,2-benzisoxazole hydrochloride (5) in a mixture of water and heptane as solvent and sodium hydroxide as a base in the presence of tetrabutylammonium bromide as a phase transfer catalyst to yield iloperidone (1) with a yield of around 95% and a purity of 99.80% by HPLC. The present work also describes the optimization details performed to achieve the process attributes responsible for high yield and purity.