IMPROVED PROCESS FOR PREPARING PALIPERIDONE, NOVEL POLYMORPHIC FORMS OF THE SAME AND PROCESS THEREOF

摘要

Disclosed herein is an improved process for producing paliperidone, wherein the process includes hydrogenating 3-(2-chloroethyl)-2-methyl-9-(hydroxyprotected)-4H- pyrido[1.2-a] pyrimidin-4-one in presence of an acid and a catalyst under hydrogen pressure to give 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H- pyrido[l,2-a]-pyrimidin-4-one and condensing 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9- hydroxy-2-methyl-4H-pyrido[l,2-a] -pyrimidin-4-one with 6-fluoro-3-(4-piperidinyl)- 1,2-benzisoxazole in presence of a base and a solvent to give paliperidone. In addition, the invention discloses novel polymorphic Forms VI and VII of paliperidone. Furthermore the invention discloses processes for producing the novel polymorphic forms and Form I from the novel polymorphic forms thereof.