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【结 构 式】 
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【分子编号】15266 【品名】4-amino-10H-thieno[2,3-b][1,5]benzodiazepine-2-carbaldehyde 【CA登记号】 |
【 分 子 式 】C12H9N3OS 【 分 子 量 】243.28908 【元素组成】C 59.24% H 3.73% N 17.27% O 6.58% S 13.18% |
合成路线1
该中间体在本合成路线中的序号：(V)3) Synthesis of 2-hydroxymethyl olanzapine: The condensation of 2-fluoronitrobenzene (I) with thiophene-2-amine (II) by means of LiOH in DMSO gives the expected secondary amine (III), which is formylated with DMF by means of POCl3 yielding the aldehyde (IV). The reducticyclization of (IV) with SnCl2 in ethanol affords 4-amino-10H-thieno[2,3-b][1,5]benzodiazepine-2-carbaldehyde (V), which is reduced with NaBH4 in ethanol to the corresponding hydroxymethyl derivative (VI). Finally, this compound is condensed with N-methylpiperazine (VII) in toluene/DMSO to give the metabolite 2-(hydroxymethyl)-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-b][1,5]benz odiazepine.
| 【1】 Calligaro, D.O.; Moore, N.A.; Tupper, D.E.; Fairhurst, J.; Hotten, T.M.; The synthesis and biological activity of some known and putative metabolites of the atypical antipsychotic agent olanzapine (LY170053). Bioorg Med Chem Lett 1997, 7, 1, 25. |
| 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) | 13463 | o-Fluoronitrobenzene; 1-fluoro-2-nitrobenzene | 1493-27-2 | C6H4FNO2 | 详情 | 详情 |
| (II) | 15263 | 2-amino-3-thiophenecarbonitrile | 4651-82-5 | C5H4N2S | 详情 | 详情 |
| (III) | 15264 | 2-(2-nitroanilino)-3-thiophenecarbonitrile | C11H7N3O2S | 详情 | 详情 | |
| (IV) | 15265 | 5-formyl-2-(2-nitroanilino)-3-thiophenecarbonitrile | C12H7N3O3S | 详情 | 详情 | |
| (V) | 15266 | 4-amino-10H-thieno[2,3-b][1,5]benzodiazepine-2-carbaldehyde | C12H9N3OS | 详情 | 详情 | |
| (VI) | 15267 | (4-amino-10H-thieno[2,3-b][1,5]benzodiazepin-2-yl)methanol | C12H11N3OS | 详情 | 详情 | |
| (VII) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |