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【结 构 式】 
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【分子编号】21035 【品名】(rac)-2-amino-5-(1,3-dioxan-2-yl)phenol 【CA登记号】 |
【 分 子 式 】C10H13NO3 【 分 子 量 】195.21816 【元素组成】C 61.53% H 6.71% N 7.17% O 24.59% |
合成路线1
该中间体在本合成路线中的序号：(IV)3-Hydroxy-4-nitrobenzaldehyde (I) was treated with 1,3-propanediol (II) in the presence of p-toluenesulfonic acid to afford the corresponding acetal (III). Catalytic hydrogenation of the nitro group of (III) over Raney-Ni gave aniline (IV), which was then acylated with chloroacetyl chloride (V) in the presence of NaHCO3 to the chloroacetamide (VI). The acetal function of (VI) was hydrolyzed with HCl in aqueous MeOH, and subsequent cyclization of the chloroacetamide (VII) using K2CO3 in acetonitrile produced the formylbenzoxazinone (VIII). The target compound was then prepared by reductive condensation of aldehyde (VIII) with N-(4-chlorophenyl)piperazine (IX) in the presence of sodium triacetoxyborohydride and AcOH.
| 【1】 Brink, W.A.; Wustrow, D.J.; Belliotti, T.R.; et al.; A series of 6- and 7-piperazinyl- and -piperidinylmethylbenzoxazinones with dopamine D4 antagonist activity: Discovery of a potential atypical antipsychotic agent. J Med Chem 1999, 42, 25, 5181. |
| 【2】 Belliotti, T.; Wise, L.D.; Wustrow, D.J. (Pfizer Inc.); Benzoxazinone dopamine D4 receptor antagonists. EP 0906294; WO 9745419 . |
| 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) | 21032 | 3-hydroxy-4-nitrobenzaldehyde | C7H5NO4 | 详情 | 详情 | |
| (III) | 21034 | 5-(1,3-dioxan-2-yl)-2-nitrophenol | C10H11NO5 | 详情 | 详情 | |
| (IV) | 21035 | (rac)-2-amino-5-(1,3-dioxan-2-yl)phenol | C10H13NO3 | 详情 | 详情 | |
| (V) | 11296 | 2-Chloroacetyl chloride; Chloroacetic chloride | 79-04-9 | C2H2Cl2O | 详情 | 详情 |
| (VI) | 21037 | 2-chloro-N-[4-(1,3-dioxan-2-yl)-2-hydroxyphenyl]acetamide | C12H14ClNO4 | 详情 | 详情 | |
| (VII) | 21038 | 2-chloro-N-(4-formyl-2-hydroxyphenyl)acetamide | C9H8ClNO3 | 详情 | 详情 | |
| (VIII) | 21039 | 3-oxo-3,4-dihydro-2H-1,4-benzoxazine-7-carbaldehyde | C9H7NO3 | 详情 | 详情 |