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【结 构 式】 
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【分子编号】16274 【品名】6-chloro-1H-indole-2,3-dione; 6-Chloroisatin 【CA登记号】6341-92-0 |
【 分 子 式 】C8H4ClNO2 【 分 子 量 】181.578 【元素组成】C 52.92% H 2.22% Cl 19.52% N 7.71% O 17.62% |
合成路线1
该中间体在本合成路线中的序号：(I)Wolff-Kishner reduction of 6-chloroisatin (I) gives 6-chlorooxindole (II), which is treated with chloroacetyl chloride under Friedel-Crafts conditions to yield 5-chloroacetyl-6-chlorooxindole (III). The ketone (III) is reduced using triethylsilane in trifluoroacetic acid to produce 6-chloro-5-(2-chloroethyl)oxindole (IV). 1,2-Benzisothiazolin-3-one (V) is converted to 3-chloro-1,2-benzisothiazole (VI) using phosphorus oxychloride and is then condensed with piperazine to provide 1-(1,2-benzisothiazol-3-yl)piperazine (VII). Finally, intermediate (VII) is alkylated by compound (IV) in the presence of sodium carbonate in water and is converted to the salt with aqueous hydrochloric acid.
| 【1】 Lowe, J.A. III; Nagel, A.A. (Pfizer Inc.); Piperazinyl-heterocyclic cpds. US 4831031 . |
| 【2】 Bowles, P. (Pfizer Inc.); Process for preparing aryl piperazinyl-heterocyclic cpds. EP 1029861; JP 1994184143; US 5206366 . |
| 【3】 Howard, H.R. Jr.; Busch, F.R.; Grobin, A.W.; Leeman, K.R. (Pfizer Products Inc.); Controlled synthesis of ziprasidone and compsns. thereof. WO 0370246 . |
| 【4】 Seeger, T.F.; Prakash, C.; Howard, H.R.; Ziprasidone Hydrochloride. Drugs Fut 1994, 19, 6, 560. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 | |
| (I) | 16274 | 6-chloro-1H-indole-2,3-dione; 6-Chloroisatin | 6341-92-0 | C8H4ClNO2 | 详情 | 详情 |
| (II) | 16275 | 6-chloro-1,3-dihydro-2H-indol-2-one | 56341-37-8 | C8H6ClNO | 详情 | 详情 |
| (III) | 16276 | 6-chloro-5-(2-chloroacetyl)-1,3-dihydro-2H-indol-2-one | C10H7Cl2NO2 | 详情 | 详情 | |
| (IV) | 16277 | 6-chloro-5-(2-chloroethyl)-1,3-dihydro-2H-indol-2-one; 5-chloroethyl-6-chloro-1,3-dihydro-1H-indol-2-one- | C10H9Cl2NO | 详情 | 详情 | |
| (V) | 16278 | 1,2-benzisothiazol-3(2H)-one; 1,2-Benzisothiazolin-3-one | 2634-33-5 | C7H5NOS | 详情 | 详情 |
| (VI) | 16279 | 3-chloro-1,2-benzisothiazole | C7H4ClNS | 详情 | 详情 | |
| (VII) | 16280 | 3-piperazino-1,2-benzisothiazole; 1,2-Benzisothiazole-3-(1-piperazinyl) | 87691-87-0 | C11H13N3S | 详情 | 详情 |