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【结 构 式】 
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【分子编号】54872 【品名】methyl 9-(chloromethyl)-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylate 【CA登记号】 |
【 分 子 式 】C14H12ClNO5 【 分 子 量 】309.70572 【元素组成】C 54.29% H 3.91% Cl 11.45% N 4.52% O 25.83% |
合成路线1
该中间体在本合成路线中的序号：(XII)In a different strategy, the dioxinoquinoline system (XII) was prepared by acylation of amino ketone (X) with methyl malonyl chloride (XI), followed by intramolecular Knoevenagel condensation of the intermediate keto malonamide. Chlorination of (XII) with POCl3 afforded the dichloro derivative (XIII), which was subsequently condensed with N-methylpiperazine (IX) to give (XIV). Reduction of the ester group of (XIV) by means of DIBAL provided alcohol (XV). Replacement of the 7-chloro of (XV) by an iodide group required previous oxidation of (XV) to the more reactive aldehyde (XVI). Treatment of (XVI) with NaI and HCl led to the corresponding iodo aldehyde, which was further reduced to alcohol (XVII) using NaBH4.
| 【1】 Fang, F.G.; Xie, S.; Lowery, M.W. (GlaxoSmithKline Inc.); Intermediates in pharmaceutical camptothecin preparation. WO 9529917 . |
| 【2】 Huie, E.M.; Fang, F.G.; Xie, S.; Comins, D.L. (GlaxoSmithKline Inc.; North Carolina State University); Preparation of a camptothecin deriv. by intramolecular cyclisation. WO 9529919 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 10061 | 1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine | 109-01-3 | C5H12N2 | 详情 | 详情 |
| (X) | 54870 | 1-(7-amino-2,3-dihydro-1,4-benzodioxin-6-yl)-2-chloro-1-ethanone | C10H10ClNO3 | 详情 | 详情 | |
| (XI) | 50272 | Malonic acid monomethyl ester chloride; Methyl (chloroformyl)acetate; Methyl malonyl chloride ;Methyl 3-chloro-3-oxopropionate | 37517-81-0 | C4H5ClO3 | 详情 | 详情 |
| (XII) | 54872 | methyl 9-(chloromethyl)-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylate | C14H12ClNO5 | 详情 | 详情 | |
| (XIII) | 54873 | methyl 7-chloro-9-(chloromethyl)-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylate | C14H11Cl2NO4 | 详情 | 详情 | |
| (XIV) | 54874 | methyl 7-chloro-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylate | C19H22ClN3O4 | 详情 | 详情 | |
| (XV) | 54875 | {7-chloro-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinolin-8-yl}methanol | C18H22ClN3O3 | 详情 | 详情 | |
| (XVI) | 54876 | 7-chloro-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carbaldehyde | C18H20ClN3O3 | 详情 | 详情 | |
| (XVII) | 54877 | {7-iodo-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinolin-8-yl}methanol | C18H22IN3O3 | 详情 | 详情 |