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【结 构 式】 
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【分子编号】55164 【品名】(6aS,12aR)-2,3-dimethoxy-6-propyl-6a,12a-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione 【CA登记号】 |
【 分 子 式 】C22H21NO6 【 分 子 量 】395.41188 【元素组成】C 66.83% H 5.35% N 3.54% O 24.28% |
合成路线1
该中间体在本合成路线中的序号：(X)Alternatively, the title compound was prepared by condensation between indanylacetic acid (IV) and thioprolylpyrrolidine (XI) either using EDC as the coupling reagent or via activation as the mixed anhydride (X) with pivaloyl chloride (IX) and triethylamine.
| 【1】 Arai, H.; Niwa, S.; Nishioka, H.; Yamanaka, T.; Torizuka, M.; Yoshinaga, K.; Kobayashi, N.; Ikeda, Y.; Tanaka, Y.; New potent prolyl endopeptidase inhibitors: Synthesis and structure-activity relationships of indan and tetralin derivatives and their analogues. J Med Chem 1994, 37, 13, 2071. |
| 【2】 Tanaka, Y.; Kobayashi, N.; Nakata, N.; Yamaguchi, I.; Mori, T. (Zeria Pharmaceutical Co., Ltd.); Cholinesterase activator. EP 0754454; JP 1995228529; US 6017929; WO 9522326 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 21721 | 2-(2,3-dihydro-1H-inden-2-yl)acetic acid | 37868-26-1 | C11H12O2 | 详情 | 详情 |
| (IX) | 13597 | 2,2-Dimethylpropanoyl chloride; Pivaloyl chloride | 3282-30-2 | C5H9ClO | 详情 | 详情 |
| (X) | 55164 | (6aS,12aR)-2,3-dimethoxy-6-propyl-6a,12a-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione | C22H21NO6 | 详情 | 详情 | |
| (XI) | 55165 | (6aS,12R,12aR)-2,3-dimethoxy-6-propyl-6,6a,12,12a-tetrahydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinolin-12-ol | C22H25NO5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)Isoquinoline (III) was prepared by the condensation of piperonal N-propylimine (I) with 4,5-dimethoxyhomophthalic anhydride (II). Subsequent intramolecular Friedel-Crafts acylation of (III) in the presence of Eaton's reagent gave rise to the indenoisoquinoline (IV). Reduction of the ketone and lactam functions of (IV) using borane-tetrahydrofuran complex provided alcohol (V). This underwent simultaneous dehydration and dehydrogenation in the presence of Pd/C in refluxing HOAc to afford, after treatment with NaCl, the target indenoisoquinolinium chloride salt.
| 【1】 Jayaraman, M.; Fox, B.M.; Hollingshead, M.; Kohlhagen, G.; Pommier, Y.; Cushman, M.; Synthesis of new dihydroindeno[1,2-c]isoquinoline and indenoisoquinolinium chloride topoisomerase I inhibitor having high in vivo anticancer activity in the hollow fiber animal model. J Med Chem 2002, 45, 1, 242. |
| 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) | 55161 | N-[(E)-1,3-benzodioxol-5-ylmethylidene]-N-propylamine; N-[(E)-1,3-benzodioxol-5-ylmethylidene]-1-propanamine | C11H13NO2 | 详情 | 详情 | |
| (II) | 55162 | 6,7-dimethoxy-1H-isochromene-1,3(4H)-dione | C11H10O5 | 详情 | 详情 | |
| (III) | 55163 | (3S,4R)-3-(1,3-benzodioxol-5-yl)-6,7-dimethoxy-1-oxo-2-propyl-1,2,3,4-tetrahydro-4-isoquinolinecarboxylic acid | C22H23NO7 | 详情 | 详情 | |
| (IV) | 55164 | (6aS,12aR)-2,3-dimethoxy-6-propyl-6a,12a-dihydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinoline-5,12(6H)-dione | C22H21NO6 | 详情 | 详情 | |
| (V) | 55165 | (6aS,12R,12aR)-2,3-dimethoxy-6-propyl-6,6a,12,12a-tetrahydro-5H-[1,3]dioxolo[4',5':5,6]indeno[1,2-c]isoquinolin-12-ol | C22H25NO5 | 详情 | 详情 |