盐酸鲁拉西酮的合成

Synthesis of Lurasidone Hydrochloride

(1R,2R)-反式-1,2-环己烷二甲酸经氯化、甲酯化、还原和磺酰化得到(1R,2R)-1,2-双(对甲苯磺酰基氧基甲基)-环己烷(9),9与3-(1-哌嗪基)-1,2-苯并异噻唑反应制得(3a R,7a R)-4'-(1,2-苯并异噻唑-3-基)八氢螺[异吲哚-2,1'-哌嗪]-对甲苯磺酸盐(10),10与顺-5-降冰片烷-外-2,3-二甲酰亚胺反应后,与盐酸成盐制得盐酸鲁拉西酮,总收率约36%。

Lurasidone hydrochloride was synthesized from I1R,2R）-cyclonexane-l,z- dicarboxylic acid by chlorination, esterification, reduction, and sulfonylation to give （1R,2R）-l,2-bis （4- toluenesulfonyloxymethyl） cyclohexane, which was subjected to condensation with 3-（piperazin-l-yl）benzo [d]- isothiazole, followed by reaction with （3aR,4S,7R,7aS）-hexahydro-lH-4,7-methanoisoindole-l,3 （2H）-dione and salification with hydrochloric acid. The overall yield was about 36%.