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【结 构 式】

【药物名称】Perospirone hydrochloride, SM-9018, Lullan

【化学名称】cis-2-[4-[4-(1,2-Benzisothiazol-3-yl)-1-piperazinyl]butyl]octahydro-1H-isoindole-1,3-dione hydrochloride

【CA登记号】129273-38-7, 150915-41-6 (free base), 105981-51-9 (free base;non-specified stereoch.), 105981-50-8 (undefined stereoch.)

【 分 子 式 】C23H31ClN4O2S

【 分 子 量 】463.04612

【开发单位】Sumitomo Pharmaceuticals (Originator), Mitsubishi Pharma (Comarketer)

【药理作用】Antipsychotic Drugs, PSYCHOPHARMACOLOGIC DRUGS, 5-HT2A Antagonists, Dopamine D2 Antagonists

合成路线1

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).

1 Ishizumi, N.; Antoku, F.; Maruyama, I.; Kojima, A. (Sumitomo Pharmaceuticals Co., Ltd.); Imide derivs., their production and use. EP 0196096; ES 8800219; JP 1987123179; JP 1987277355; JP 1987277356; US 4745117 .
2 Prous, J.; Castaner, J.; SM-9018. Drugs Fut 1991, 16, 2, 122.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 27329 (3aR,7aS)hexahydro-2-benzofuran-1,3-dione 13149-00-3 C8H10O3 详情 详情
(II) 31245 (3aR,7aS)hexahydro-1H-isoindole-1,3(2H)-dione 7506-66-3 C8H11NO2 详情 详情
(III) 11883 1,4-Dibromobutane; 1,4-Butylene bromide 110-52-1 C4H8Br2 详情 详情
(IV) 31246 (3aR,7aS)-2-(4-bromobutyl)hexahydro-1H-isoindole-1,3(2H)-dione C12H18BrNO2 详情 详情
(V) 10355 Diethylenediamine; Piperazine 110-85-0 C4H10N2 详情 详情
(VI) 31247 (3aR,7aS)-2-[4-(1-piperazinyl)butyl]hexahydro-1H-isoindole-1,3(2H)-dione C16H27N3O2 详情 详情
(VII) 16279 3-chloro-1,2-benzisothiazole C7H4ClNS 详情 详情
(VIII) 16280 3-piperazino-1,2-benzisothiazole; 1,2-Benzisothiazole-3-(1-piperazinyl) 87691-87-0 C11H13N3S 详情 详情
(IX) 20404 2-[(2-carboxyphenyl)disulfanyl]benzoic acid; 2,2'-Dithiodibenzoic acid 119-80-2 C14H10O4S2 详情 详情
(X) 20405 2-[[2-(chlorocarbonyl)phenyl]disulfanyl]benzoyl chloride C14H8Cl2O2S2 详情 详情
(XI) 31248 N-methyl-2-([2-[(methylamino)carbonyl]phenyl]disulfanyl)benzamide 2527-58-4 C16H16N2O2S2 详情 详情
(XII) 31249 3-chloro-2-methyl-1,2-benzisothiazol-2-ium chloride C8H7Cl2NS 详情 详情
Extended Information