| 摘要 |
<p>Disclosed is a process for preparing 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one comprising: a) preparing 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one comprising reacting 3-(2-chloroethyl)-2-methyl-9-(phenylmethoxy)-4H-pyrido[1,2-a]pyrimidin-4-one or 3-(2-chloroethyl)-2-methyl-9-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one with hydrogen and a hydrogenation catalyst in an acidic medium to form 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one, removing the acidic media from step (i) and isolating 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-4H-pyrido[1,2-a]pyrimidin-4-one with a solvent selected from the group consisting of ketones, alcohols, water, hydrocarbons and mixtures thereof; b) reacting 3-(2-chloroethyl)-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one with 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole·HCI in the presence of a base and an inert solvent selected from the group consisting of alcohols, ketones, esters, ethers, hydrocarbons and mixtures thereof; c) removing the solvent from step (b) and d) isolating paliperidone from a solvent selected from the group consisting of ketones, alcohols, water, hydrocarbons and mixtures thereof.</p> |
