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【结 构 式】 
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【药物名称】QF-1004B 【化学名称】6-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)piperidin-1-ylmethyl]-6,7-dihydrobenzofuran-4(5H)-one 【CA登记号】 【 分 子 式 】C21H21FN2O3 【 分 子 量 】368.41152 |
【开发单位】Universidad de Santiago de Compostela (Originator), Università degli Studi di Pisa (Originator) 【药理作用】Antipsychotic Drugs, PSYCHOPHARMACOLOGIC DRUGS, 5-HT2 Receptor Ligands, Dopamine D1 Antagonists, Dopamine D2 Antagonists, Dopamine D4 Antagonists |
合成路线1
Acidic hydrolysis of the enol ether groups of 1,4-dihydro-3,5-dimethoxybenzyl alcohol (I) gave diketone (II). Subsequent condensation of (II) with chloroacetaldehyde in the presence of NaHCO3, followed by dehydration of the intermediate (III) upon acidic treatment, yielded the tetrahydrobenzofuranone (IV). Tosylate (V) was then prepared by reaction of alcohol (IV) with p-toluenesulfonyl chloride in cold pyridine. Finally, nucleophilic displacement of the tosylate group with benzisoxazolylpiperidine (VI) in N-methylpyrrolidone provided the title amine.
| 【1】 Casariego, I.; et al.; New CNS agent precursors. A simple and efficient route for synthesis of 6-aminomethyl-4,5,6,7-tetrahydrobenzofuran-4-ones as conformationally constrained butyrophenone analogues. Tetrahedron Lett 1997, 38, 31, 5555. |
| 【2】 Masaguer, C.F.; Casariego, I.; Raviña, E.; et al.; Conformationally constrained butyrophenones with affinity for dopamine (D1, D2, D4) and serotonin (5-HT2A, 5-HT2C) receptors: Synthesis of aminomethylbenzo[b]furanones and their evaluation as antipsychotics. J Med Chem 2000, 43, 24, 4678. |
| 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) | 25566 | (3,5-dimethoxy-2,5-cyclohexadien-1-yl)methanol | C9H14O3 | 详情 | 详情 | |
| (II) | 47758 | 5-(hydroxymethyl)-1,3-cyclohexanedione | C7H10O3 | 详情 | 详情 | |
| (III) | 47759 | 2-[4-(hydroxymethyl)-2,6-dioxocyclohexyl]acetaldehyde | C9H12O4 | 详情 | 详情 | |
| (IV) | 47760 | 6-(hydroxymethyl)-6,7-dihydro-1-benzofuran-4(5H)-one | C9H10O3 | 详情 | 详情 | |
| (V) | 47761 | (4-oxo-4,5,6,7-tetrahydro-1-benzofuran-6-yl)methyl 4-methylbenzenesulfonate | C16H16O5S | 详情 | 详情 | |
| (VI) | 17910 | 6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole | C12H13FN2O | 详情 | 详情 |