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【结 构 式】 
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【分子编号】26821 【品名】7-(3-chloropropoxy)-4-oxo-4H-chromene-3-carbaldehyde 【CA登记号】 |
【 分 子 式 】C13H11ClO4 【 分 子 量 】266.68064 【元素组成】C 58.55% H 4.16% Cl 13.29% O 24% |
合成路线1
该中间体在本合成路线中的序号：(IV)2',4'-Dihydroxyacetophenone (I) was selectively alkylated at position 4' with 1-bromo-3-chloropropane (II) in the presence of K2CO3 in refluxing acetone to yield the 4'-(3-chloropropyl)ether (III). Further condensation of (III) with Vilsmeier reagent, followed by aqueous work up, provided the 3-formylchromenone (IV), which was subsequently reduced with sodium borohydride in CHCl3-EtOH at 0 C to give the (hydroxymethyl)chromenone (V). Finally, alkylation of 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole (VI) with chloride (V) in the presence of K2CO3 and KI in refluxing acetonitrile yielded the title compound, which was isolated as the hydrochloride salt from methanol.
| 【1】 Princep, M.; Guglietta, A.; Bolos, J.; Abaperidone Hydrochloride. Drugs Fut 2001, 26, 4, 335. |
| 【2】 Bolos, J.; et al.; 7-[3-(1-Piperidinyl)propoxy]chromenones as potential atypical antipsychotics. J Med Chem 1996, 39, 15, 2962. |
| 【3】 Bolós, J.; Anglada, L.; Gubert, S.; Planas, J.M.; Agut, J.; Princep, M.; De la Fuente, N.; Sacristan, A.; Ortiz, J.A.; 7-[3-(1-Piperidinyl)propoxy]chromenones as potential atypical antipsychotics. 2. Pharmacological profile of 7-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (abaperidone, FI-8602). J Med Chem 1998, 41, 27, 5402. |
| 【4】 Foguet, R.; Anglada, L.; Bolós, J.; Ortiz, J.; Sacristán, A.; Castellò, J.M. (Ferrer Internacional SA); 4-(6-Fluoro-1, 2-benzisoxazolyl)-1-piperidinyl-propoxy-chromen-4-one derivs., their preparation and their use in the treatment of psychosis, schizophrenia and anxiety. EP 0765323; ES 2101646; ES 2103237; JP 1998501557; US 5736558; WO 9632389 . |
| 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) | 13961 | Resacetophenone; 1-(2,4-Dihydroxyphenyl)-1-ethanone | 89-84-9 | C8H8O3 | 详情 | 详情 |
| (II) | 10358 | 1-Bromo-3-chloropropane | 109-70-6 | C3H6BrCl | 详情 | 详情 |
| (III) | 26820 | 1-[4-(3-chloropropoxy)-2-hydroxyphenyl]-1-ethanone | C11H13ClO3 | 详情 | 详情 | |
| (IV) | 26821 | 7-(3-chloropropoxy)-4-oxo-4H-chromene-3-carbaldehyde | C13H11ClO4 | 详情 | 详情 | |
| (V) | 26822 | 7-(3-chloropropoxy)-3-(hydroxymethyl)-4H-chromen-4-one | C13H13ClO4 | 详情 | 详情 | |
| (VI) | 17910 | 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole | C12H13FN2O | 详情 | 详情 |