|
【结 构 式】 
|
【药物名称】KCA-098 【化学名称】3,9-Bis(N,N-dimethylcarbamoyloxy)benzofuro[3,2-c]quinolin-6(5H)-one 【CA登记号】129794-24-7 【 分 子 式 】C21H19N3O6 【 分 子 量 】409.40208 |
【开发单位】Kissei (Originator) 【药理作用】Bone Diseases, Treatment of, Bone Resorption Inhibitors, METABOLIC DRUGS, Treatment of Osteoporosis |
合成路线1
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 |