【结 构 式】 |
【分子编号】49537 【品名】8-methyl-9-oxo-9,11-dihydroindolizino[1,2-b]quinoline-7-carbaldehyde 【CA登记号】 |
【 分 子 式 】C17H12N2O2 【 分 子 量 】276.29456 【元素组成】C 73.9% H 4.38% N 10.14% O 11.58% |
合成路线1
该中间体在本合成路线中的序号:(XIV)The condensation of the 2-chloroquinoline-3-methanol (I) with trimethylsilyl acetylene (II) by means of PdCl2(PPh3)2 and CuI in DMF gives 2-(trimethylsilylethynyl)quinoline-3-methanol (III), which is treated with PPh3, CBr4 and sodium azide to yield the azidomethyl derivative (IV). The reduction of (IV) with PPh3 in THF/water affords the aminomethyl compound (V), which is condensed with fumaric acid monoethyl ester (VI) by means of BOP in acetonitrile to provide the amide (VII). The cyclization of (VII) by means of Tms-Cl, DIEA and ZnCl2 in toluene at 180 C in a sealed tube gives the tetracyclic ester (VIII), which is treated with HBr in ethyl acetate to yield the intermediate ethyl ester (IX). The transesterification of (IX) catalyzed by H2SO4 in refluxing methanol affords the methyl ester (X), which is methylated with diazomethane to provide 2-methyl-1-oxo-1,11-dihydroindolizino[1,2-b]quinoline-3-carboxylic acid methyl ester (XI). The reduction of (XI) with LiBH4 in hot bis(2-methoxyethyl)ether gives the tetracyclic carbinol (XII), which is oxidized with DMSO in hot Ac2O to yield the carbaldehyde (XIII). Finally, this compound is treated with diazoethane in ethyl ether to afford the target propionyl derivative.
【1】 Kametani, T.; et al.; Studies on the syntheses of heterocyclic compounds. Part DCXXII. Total synthesis of (±)-mappicine [7-(1-hydroxypropyl)-8-methylindolizino[1,2-b]quinolin-9(11H)-one]. J Chem Soc - Perkins Trans I 1975, 1825. |
【2】 Toyota, M.; et al.; A concise formal total synthesis of mappicine and nothapodytine B via and intramolecular hetero Diels-Alder reaction. J Org Chem 2000, 65, 21, 7110. |
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) | 49526 | (2-chloro-3-quinolinyl)methanol | C10H8ClNO | 详情 | 详情 | |
(II) | 23897 | ethynyl(trimethyl)silane;trimethylsilyl acetylene | 1066-54-2 | C5H10Si | 详情 | 详情 |
(III) | 49527 | [2-[2-(trimethylsilyl)ethynyl]-3-quinolinyl]methanol | C15H17NOSi | 详情 | 详情 | |
(IV) | 49528 | 3-(azidomethyl)-2-[2-(trimethylsilyl)ethynyl]quinoline; [2-[2-(trimethylsilyl)ethynyl]-3-quinolinyl]methyl azide | C15H16N4Si | 详情 | 详情 | |
(V) | 49529 | [2-[2-(trimethylsilyl)ethynyl]-3-quinolinyl]methylamine; [2-[2-(trimethylsilyl)ethynyl]-3-quinolinyl]methanamine | C15H18N2Si | 详情 | 详情 | |
(VI) | 49530 | Fumaric acid monoethyl ester; Ethyl hydrogen fumarate; Ethyl Fumarate Monoester; Monoethyl fumarate | 2459-05-4 | C6H8O4 | 详情 | 详情 |
(VII) | 49531 | ethyl (E)-4-oxo-4-[([2-[2-(trimethylsilyl)ethynyl]-3-quinolinyl]methyl)amino]-2-butenoate | C21H24N2O3Si | 详情 | 详情 | |
(VIII) | 49532 | ethyl 9-oxo-6-(trimethylsilyl)-7,8,9,11-tetrahydroindolizino[1,2-b]quinoline-7-carboxylate | C21H24N2O3Si | 详情 | 详情 | |
(IX) | 49533 | ethyl 9-oxo-9,11-dihydroindolizino[1,2-b]quinoline-7-carboxylate | C18H14N2O3 | 详情 | 详情 | |
(X) | 49534 | methyl 9-oxo-9,11-dihydroindolizino[1,2-b]quinoline-7-carboxylate | C17H12N2O3 | 详情 | 详情 | |
(XII) | 49535 | methyl 8-methyl-9-oxo-9,11-dihydroindolizino[1,2-b]quinoline-7-carboxylate | C18H14N2O3 | 详情 | 详情 | |
(XIII) | 49536 | 7-(hydroxymethyl)-8-methylindolizino[1,2-b]quinolin-9(11H)-one | C17H14N2O2 | 详情 | 详情 | |
(XIV) | 49537 | 8-methyl-9-oxo-9,11-dihydroindolizino[1,2-b]quinoline-7-carbaldehyde | C17H12N2O2 | 详情 | 详情 | |
(XV) | 49538 | C2H4N2 | 详情 | 详情 |