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【结 构 式】 
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【分子编号】31890 【品名】1-chloro-N-[2-(dimethylamino)ethyl]-7-methoxy-9-oxo-9,10-dihydro-4-acridinecarboxamide 【CA登记号】 |
【 分 子 式 】C19H20ClN3O3 【 分 子 量 】373.83892 【元素组成】C 61.04% H 5.39% Cl 9.48% N 11.24% O 12.84% |
合成路线1
该中间体在本合成路线中的序号：(VI)The reaction of 2-bromo-5-methoxybenzoic acid (I) with ethyl 2-amino-4-chlorobenzoate (II) by means of Cu(OAc)2 and 1-methyl-2-pyrrolidone in DIEA, followed by cyclization by means of polyphosphoric acid ethyl ester in refluxing chloroform gives the acridone (III), which is hydrolyzed with NaOH in refluxing ethanol yielding the carboxylic acid (IV). The condensation of (IV) with N,N-dimethylethylenediamine (V) by means of CDI in DMF affords the corresponding amide (VI), which is cyclized with phosgene in chloroform to provide the pyrimidoacridinetrione (VII). The reaction of (VII) with N,N-dimethyleythylenediamine (V) gives the final intermediate (VIII), which is demethylated with refluxing 48% HBr.
| 【1】 Polucci, P.; Antonini, I.; Kelland, L.R.; Menta, E.; Pescalli, N.; Martelli, S.; 2,3-Dihydro-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7-trione derivatives, a class of cytotoxic agents active on multidrug-resistant cell lines: Synthesis, biological evaluation, and structure-activity relationships. J Med Chem 1999, 42, 14, 2535. |
| 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) | 17189 | (3S)-5-oxotetrahydro-1H-pyrrol-3-yl methanesulfonate | C5H9NO4S | 详情 | 详情 | |
| (II) | 31887 | ethyl 2-amino-4-chlorobenzoate | C9H10ClNO2 | 详情 | 详情 | |
| (III) | 31888 | ethyl 1-chloro-7-methoxy-9-oxo-9,10-dihydro-4-acridinecarboxylate | C17H14ClNO4 | 详情 | 详情 | |
| (IV) | 31889 | 1-chloro-7-methoxy-9-oxo-9,10-dihydro-4-acridinecarboxylic acid | C15H10ClNO4 | 详情 | 详情 | |
| (V) | 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 |
| (VI) | 31890 | 1-chloro-N-[2-(dimethylamino)ethyl]-7-methoxy-9-oxo-9,10-dihydro-4-acridinecarboxamide | C19H20ClN3O3 | 详情 | 详情 | |
| (VII) | 31891 | 6-chloro-2-[2-(dimethylamino)ethyl]-9-methoxy-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7(2H)-trione | C20H18ClN3O4 | 详情 | 详情 | |
| (VIII) | 31892 | 2-[2-(dimethylamino)ethyl]-6-[[2-(dimethylamino)ethyl]amino]-9-methoxy-1H,7H-pyrimido[5,6,1-de]acridine-1,3,7(2H)-trione | C24H29N5O4 | 详情 | 详情 |