【结 构 式】 |
【药物名称】SN-22977, NSC-683247, AMAC 【化学名称】9-Amino-N-[2-(dimethylamino)ethyl]-5-methylacridine-4-carboxamide 【CA登记号】 【 分 子 式 】C19H22N4O 【 分 子 量 】322.41339 |
【开发单位】University of Auckland (Originator) 【药理作用】ONCOLYTIC DRUGS, DNA-Intercalating Drugs |
合成路线1
The intermediate 6-methyldiphenylamine-2,2'-dicarboxylic acid (V) has been synthesized in two similar ways. 1. By Jourdan-Ullman copper-catalyzed condensation of 6-methylbenzoic acid (I) with 2-aminobenzoic acid (II); and 2. By the same type of condensation, but using 2-amino-3-methylbenzoic acid (III) and 2-chlorobenzoic acid (IV). The cyclization of the intermediate dicarboxylic acid (V) under acidic conditions gives 5-methyl-9-oxo-9,10-dihydroacridine-4-carboxylic acid (VI), which is treated with hot SOCl2 and DMF to yield 9-choloro-5-methylacridine-4-carbonyl chloride (VII). The reaction of (VII) with N,N-dimethylethylenediamine (VIII) in dichloromethane affords the corresponding amide (IX), which is finally treated first with phenol at 100 C and then with a stream of dry ammonia at 110-20 C to obtain the target 9-aminoacridine derivative.
【1】 Rewcastle, G.W.; et al.; Potential antitumor agents. 46. Structure-activity relationships for acridine monosubstituted derivatives of the antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide. J Med Chem 1986, 29, 4, 472. |
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) | 51949 | 2-Chloro-3-methylbenzoic acid | 15068-35-6 | C8H7ClO2 | 详情 | 详情 |
(II) | 11661 | 2-Aminobenzoic acid;Anthranilic acid; o-Aminobenzoic acid | 118-92-3 | C7H7NO2 | 详情 | 详情 |
(III) | 48130 | 2-amino-3-methylbenzoic acid | 4389-45-1 | C8H9NO2 | 详情 | 详情 |
(IV) | 10203 | o-Chlorobenzoic acid; 2-Chlorobenzoic acid | 118-91-2 | C7H5ClO2 | 详情 | 详情 |
(V) | 51950 | 2-(2-carboxyanilino)-3-methylbenzoic acid | C15H13NO4 | 详情 | 详情 | |
(VI) | 30493 | 5-methyl-9-oxo-9,10-dihydro-4-acridinecarboxylic acid | C15H11NO3 | 详情 | 详情 | |
(VII) | 30494 | 9-chloro-5-methyl-4-acridinecarbonyl chloride | C15H9Cl2NO | 详情 | 详情 | |
(VIII) | 14481 | (6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carbothioic S-acid | C21H26F2O4S | 详情 | 详情 | |
(IX) | 51951 | 9-chloro-N-[2-(dimethylamino)ethyl]-5-methyl-4-acridinecarboxamide | C19H20ClN3O | 详情 | 详情 |