Perospirone hydrochloride, SM-9018, Lullan

盐酸哌罗匹隆 哌罗匹隆 Chemical Name: cis-2-[4-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl]butyl]octahydro-1H-isoindole-1,3-dione hydrochloride
CAS No. 129273-38-7, 150915-41-6 (free base), 105981-51-9 (free base, non-specified stereoch.), 105981-50-8 (undefined stereoch.)
项目整合开发状态: Launched-2001
项目研究机构: Sumitomo Pharmaceuticals (Originator), Mitsubishi Pharma (Comarketer)
合成路线:This compound can be obtained by two related ways:1) The reaction of cis-octahydroisobenzofuran-1,3-dione (I) with ammonia in water at 180-90 gives cis-octahydro-1H-isoindole-1,3-dione (II),which is alkylated with 1,4-dibromobutane (III) and K2CO3 in refluxing acetone to yield cis-2-(4-bromobutyl)octahydro-1H-isoindole-1,3-dione (IV).The condensation of (IV) with piperazine (V) in refluxing toluene affords cis-2-(4-piperazinobutyl)octahydro-1H-isoindole-1,3-dione (VI),which is finally condensed with 3-chloro-1,2-benzisothiazole (VII) and K2CO3 in refluxing toluene.2) The condensation of benzisothiazole (VII) with piperazine (V) by heating at 120 C gives 3-piperazino-1,2-benzisothiazole (VIII),which is then condensed with isoindole (IV) by means of K2CO3 and KI in hot DMF.3) The 3-chloro-1,2-benzisothiazole (VII) is obtained as follows: The reaction of 2,2'-dithiobenzoic acid (IX) with refluxing SOCl2 gives the corresponding acyl chloride (X),which by treatment with methylamine in THF is converted into the diamide (XI).The reaction of (XI) with PCl5 in refluxing benzene affords 3-chloro-2-methyl-1,2-benzisothiazolium chloride (XII),which is finally heated in refluxing 1,2-dichlorobenzene to give (VII).