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【结 构 式】 
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【分子编号】13704 【品名】3-Methoxyphenylamine; 3-Methoxyaniline; m-Anisidine 【CA登记号】536-90-3 |
【 分 子 式 】C7H9NO 【 分 子 量 】123.1546 【元素组成】C 68.27% H 7.37% N 11.37% O 12.99% |
合成路线1
该中间体在本合成路线中的序号：(I)The cyclization of m-anisidine (I) with 2,4-dimethoxyphenylmalonic acid diethyl ester (II) in refluxing diphenyl ether (270-90 C) gives 3-(2,4-dimethoxyphenyl)-4-hydroxy-7-methoxyquinolin-2-(1H)-one (III), which is submitted to a new cyclization process in refluxing 47% aqueous HBr yielding 3,9-dihydroxybenzofuro[3,2-c]quinolin-6-(5H)-one (IV). Finally, this compound is esterified with N,N-dimethylcarbamoyl chloride (V) by means of triethylamine and dimethylaminopyridine (DMAP) in DMF.
| 【1】 Rabasseda, X.; Castaner, J.; Mealy, N.; KCA-098. Drugs Fut 1995, 20, 3, 235. |
| 【2】 Kamijo, T.; Ujiie, A.; Harada, H.; Tsutsumi, N.; Tsubaki, A.; Yamaguchi, T.; Nagata, H. (Kissei Pharmaceutical Co., Ltd.); Benzofuro[3,2-c]quinoline cpds. AU 8930977; EP 0357172; JP 1990062878; US 5023261 . |
| 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) | 13704 | 3-Methoxyphenylamine; 3-Methoxyaniline; m-Anisidine | 536-90-3 | C7H9NO | 详情 | 详情 |
| (II) | 13705 | diethyl 2-(2,4-dimethoxyphenyl)malonate | C15H20O6 | 详情 | 详情 | |
| (III) | 13706 | 3-(2,4-Dimethoxyphenyl)-4-hydroxy-7-methoxy-2(1H)-quinolinone | C18H17NO5 | 详情 | 详情 | |
| (IV) | 13707 | 3,9-Dihydroxy[1]benzofuro[3,2-c]quinolin-6(5H)-one | C15H9NO4 | 详情 | 详情 | |
| (V) | 13708 | N,N'-Dimethylcarbamoyl chloride; Dimethylcarbamoyl chloride; [(Chlorocarbonyl)(methyl)amino]methane | 79-44-7 | C3H6ClNO | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The condensation of 1,3-dioxoindane-2-carboxylic acid ethyl ester (I) with m-anisidine (II) in refluxing toluene gives the corresponding amide (III), which is cyclized with polyphosphoric acid (PPA) at 120 C yielding 3-methoxy-6,7-dihydro-5H-indeno[2,1-c]quinoline-6,7-dione (IV). The reaction of (IV) with refluxing POCl3 affords the chloroketone (V), which is condensed with 2-(dimethylamino)ethylamine (VI) in pyridine at 100 C giving the aminoketone (VII). Finally, this compound is demethylated with concentrated HBr in refluxing acetic acid.
| 【1】 Castañer, J.; Hoshi, A.; TAS-103. Drugs Fut 1998, 23, 5, 513. |
| 【2】 Ishida, K.; Wakida, M.; Utsugi, T.; Okazaki, S.; Yamada, Y.; Asano, T.; Synthesis of novel indeno[2,1-c]quinolin-7-one derivatives and their topoisomerase inhibitory and antitumor activities. 17th Symp Med Chem/6th Annu Meet Div Med Chem/2nd Conf Drug Discov (Nov 19-21, Tsukuba) 1997, Abst 2-P-05.. |
| 【3】 Okazaki, S.; Asao, T.; Wakida, M.; Ishida, K.; Washinosu, M.; Utsugi, T.; Yamada, Y. (Taiho Pharmaceutical Co., Ltd.); Novel fused indan deriv. and pharmaceutically acceptable salt. EP 0713870; US 5710162; US 5733918; WO 9532187 . |
| 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) | 17166 | ethyl 1,3-dioxo-2-indanecarboxylate | C12H10O4 | 详情 | 详情 | |
| (II) | 13704 | 3-Methoxyphenylamine; 3-Methoxyaniline; m-Anisidine | 536-90-3 | C7H9NO | 详情 | 详情 |
| (III) | 17168 | N-(3-methoxyphenyl)-1,3-dioxo-2-indanecarboxamide | C17H13NO4 | 详情 | 详情 | |
| (IV) | 17169 | 3-methoxy-5H-indeno[2,1-c]quinoline-6,7-dione | C17H11NO3 | 详情 | 详情 | |
| (V) | 17170 | 6-chloro-3-methoxy-7H-indeno[2,1-c]quinolin-7-one | C17H10ClNO2 | 详情 | 详情 | |
| (VI) | 14881 | N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine | 108-00-9 | C4H12N2 | 详情 | 详情 |
| (VII) | 17172 | 6-[[2-(dimethylamino)ethyl]amino]-3-methoxy-7H-indeno[2,1-c]quinolin-7-one | C21H21N3O2 | 详情 | 详情 |