【结 构 式】 |
【分子编号】31249 【品名】3-chloro-2-methyl-1,2-benzisothiazol-2-ium chloride 【CA登记号】 |
【 分 子 式 】C8H7Cl2NS 【 分 子 量 】220.12172 【元素组成】C 43.65% H 3.21% Cl 32.21% N 6.36% S 14.57% |
合成路线1
该中间体在本合成路线中的序号:(XII)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 |