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【结 构 式】 
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【药物名称】NSC-697887(free acid), NSC-656889, XK-469 【化学名称】(±)-2-[4-(7-Chloroquinoxalin-2-yloxy)phenoxy]propionic acid sodium salt 【CA登记号】157434-99-6, 157542-90-0 ((S)-isomer), 157435-10-4 (free acid), 157542-91-1 (free acid;(R)-isomer), 157542-92-2 (free acid;(S)-i 【 分 子 式 】C17H12ClN2NaO4 【 分 子 量 】366.73899 |
【开发单位】Bristol-Myers Squibb (Originator) 【药理作用】Oncolytic Drugs, Solid Tumors Therapy, DNA Topoisomerase II Inhibitors, DNA-Intercalating Drugs |
合成路线1
The cyclization of 4-chlorophenylene-1,2-diamine (I) with glyoxylic acid (II) in isopropanol gives a mixture of 7-chloroquinoxalin-2-ol (III) and 6-chloroquinoxalin-2-ol (IV), which, without isolation is treated with refluxing POCl3, and the resulting mixture of dichloro compounds is submitted to flash chromatography to obtain the desired 2,7-dichloroquinoxaline (V). The condensation of (V) with 2-(4-hydroxyphenoxy)propionic acid methyl ester (VI) by means of K2CO3 in refluxing acetone affords the ester precursor (VII), which is hydrolyzed with KOH in THF/water and acidified with HCl to provide the racemic 2-[4-(7-chloroquinoxalin-2-yloxy)phenoxy]propionic acid (VIII). Finally, this compound is converted into its sodium salt with NaOH in water.
| 【1】 Behrens, C.H.; Dusak, B.A.; Harrison, B.A.; Orwat, M.J. (Bristol-Myers Squibb Co.); (2-Quinoxalinyloxy)phenoxypropanoic acids and related derivs. as anticancer agents. WO 9413647 . |
| 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) | 55570 | 2-Amino-5-chlorobenzamide; 3,4-Diaminochlorobenzene; 4-Chloro-1,2-diaminobenzene; 4-Chloro-1,2-phenylenediamine; 4-Chloro-o-phenylenediamine | 95-83-0 | C6H7ClN2 | 详情 | 详情 |
| (II) | 15618 | 2-Oxoacetic acid; Glyoxylic Acid | 298-12-4 | C2H2O3 | 详情 | 详情 |
| (III) | 56728 | 7-chloro-2-quinoxalinol | C8H5ClN2O | 详情 | 详情 | |
| (IV) | 56729 | 6-chloro-2-quinoxalinol | C8H5ClN2O | 详情 | 详情 | |
| (V) | 56725 | 2,7-dichloroquinoxaline | 59489-31-5 | C8H4Cl2N2 | 详情 | 详情 |
| (VI) | 56730 | Methyl D-2-(4-hydroxyphenoxy)propionate | 96562-58-2 | C10H12O4 | 详情 | 详情 |
| (VII) | 56731 | methyl 2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propanoate | C18H15ClN2O4 | 详情 | 详情 | |
| (VIII) | 56732 | 2-{4-[(7-chloro-2-quinoxalinyl)oxy]phenoxy}propanoic acid | C17H13ClN2O4 | 详情 | 详情 |