【结 构 式】 |
【分子编号】20431 【品名】7-chloropyrrolo[2,1-b][1,3]benzothiazepin-9(10H)-one 【CA登记号】 |
【 分 子 式 】C12H8ClNOS 【 分 子 量 】249.72036 【元素组成】C 57.72% H 3.23% Cl 14.2% N 5.61% O 6.41% S 12.84% |
合成路线1
该中间体在本合成路线中的序号:(IX)Friedel-Crafts acetylation of 4-chlorothioanisole (I) gave acetophenone (II), which was then brominated to afford the corresponding bromoketone (III). Further reaction of (III) with hexamethylenetetramine, followed by acid hydrolysis yielded the aminoketone (IV). The Clauson-Kaas reaction of amine (IV) with 2,5-dimethoxytetrahydrofuran (V) in the presence of AcOH-AcONa provided pyrrole (VI), and then the thioether function of (VI) was oxidized to sulfoxide (VII) with sodium periodate. The subsequent Pummerer cyclization using trifluoroacetic anhydride produced an intermediate tricyclic sulfonium salt (VIII) that, upon losing a methyl group, yielded the pyrrolobenzothiazepine (IX). Reduction of the ketone function of (IX) to alcohol (X) with NaBH4, followed by treatment with PBr3, furnished bromide (XI). Finally, displacement of the bromide of (XI) at 130 C with N-methylpiperazine (XII) provided the title compound, which was isolated as the dihydrochloride salt on treating with methanolic HCl.
【1】 Campiani, G.; Nacci, V.; Bechelli, S.; Ciani, S.M.; Garofalo, A.; Fiorini, I.; Wikstrom, H.; de Boer, P.; Liao, Y.; Tepper, P.G.; Cagnotto, A.; Mennini, T.; New antipsychotic agents with serotonin and dopamine antagonist properties based on a pyrrolo[2,1-b][1,3]benzothiazepine structure. J Med Chem 1998, 41, 20, 3763. |
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) | 20423 | 4-chlorophenyl methyl sulfide; 1-chloro-4-(methylsulfanyl)benzene | 123-09-1 | C7H7ClS | 详情 | 详情 |
(II) | 20424 | 1-[5-chloro-2-(methylsulfanyl)phenyl]-1-ethanone | C9H9ClOS | 详情 | 详情 | |
(III) | 20425 | 2-bromo-1-[5-chloro-2-(methylsulfanyl)phenyl]-1-ethanone | C9H8BrClOS | 详情 | 详情 | |
(IV) | 20426 | 2-amino-1-[5-chloro-2-(methylsulfanyl)phenyl]-1-ethanone | C9H10ClNOS | 详情 | 详情 | |
(V) | 12132 | 2,5-Dimethoxytetrahydrofuran; 5-Methoxytetrahydro-2-furanyl methyl ether | 696-59-3 | C6H12O3 | 详情 | 详情 |
(VI) | 20428 | 1-[5-chloro-2-(methylsulfanyl)phenyl]-2-(1H-pyrrol-1-yl)-1-ethanone | C13H12ClNOS | 详情 | 详情 | |
(VII) | 20429 | 1-[5-chloro-2-(methylsulfinyl)phenyl]-2-(1H-pyrrol-1-yl)-1-ethanone | C13H12ClNO2S | 详情 | 详情 | |
(VIII) | 20430 | 7-chloro-4-methyl-9-oxo-9,10-dihydropyrrolo[2,1-b][1,3]benzothiazepin-4-ium | C13H11ClNOS | 详情 | 详情 | |
(IX) | 20431 | 7-chloropyrrolo[2,1-b][1,3]benzothiazepin-9(10H)-one | C12H8ClNOS | 详情 | 详情 | |
(X) | 20432 | 7-chloro-9,10-dihydropyrrolo[2,1-b][1,3]benzothiazepin-9-ol | C12H10ClNOS | 详情 | 详情 | |
(XI) | 20433 | 9-bromo-7-chloro-9,10-dihydropyrrolo[2,1-b][1,3]benzothiazepine | C12H9BrClNS | 详情 | 详情 | |
(XII) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |