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【结 构 式】 
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【药物名称】Ritolukast, Wy-48252 【化学名称】1,1,1-Trifluoro-N-[3-(2-quinolinylmethoxy)phenyl]methanesulfonamide 【CA登记号】111974-60-8 【 分 子 式 】C17H13F3N2O3S 【 分 子 量 】382.36396 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Leukotriene CysLT1 (LTD4) Antagonists, Lipoxygenase Inhibitors |
合成路线1
Alkylation of 3-aminophenol (I) with 2-(chloromethyl)quinoline (A) in a mixture of DMSO and THF employing sodium hydride as the base affords the intermediate amine (II). This amine is reacted with trifluoromethanesulfonic anhydride in toluene employing potassium carbonate as a base to afford ritolukast.
| 【1】 Musser, J.H.; Kubrak, D.M.; Kreft, A.F. (American Home Products Corp.); Quinoline compounds as antiallergy and antithrombotic agents. EP 0232954; GB 2185741; JP 1987190159; US 4675405 . |
| 【2】 Kreft, A.; Musser, J.; Daniel, W.C.; Hand, J.; RITOLUKAST < USAN >. Drugs Fut 1990, 15, 12, 1191. |
| 【3】 Musser, J.H.; Kreft, A.F.; Bender, R.H.W.; Kubrak, D.M.; Carlson, R.P.; Chang, J.; Hand, J.M.; N-[(Arylmethoxy)phenyl] and N-[(arylmethoxy)naphthyl]sulfonamides. Potent orally active leukotriene D4 antagonists of novel structure. J Med Chem 1989, 32, 6, 1176. |
合成路线2
The reaction of 2-(chloromethyl)quinoline (I) with 3-nitrophenol (II) by means of Cs2CO3 in refluxing acetone gives the 3-nitrophenyl ether (III), which is reduced with H2 over Raney-Ni in ethanol to afford the 3-aminophenyl ether (IV). Finally this compound is sulfonated with trifluoromethanesulfonic anhydride and Et3N in dichloromethane.
| 【1】 Kreft, A.; Musser, J.; Substituted-[2-quinolynil(bridged)aryl] compounds: modulators of eicosanoid biosynthesis and action. Drugs Fut 1990, 15, 1, 73. |
| 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) | 13162 | 2-(Chloromethyl)quinoline; alpha-Chloroquinaldine | 4377-41-7 | C10H8ClN | 详情 | 详情 |
| (II) | 18076 | Metanitrophenol; 3-nitrophenol | 554-84-7 | C6H5NO3 | 详情 | 详情 |
| (III) | 43199 | 3-nitrophenyl 2-quinolinylmethyl ether; 2-[(3-nitrophenoxy)methyl]quinoline | C16H12N2O3 | 详情 | 详情 | |
| (IV) | 31234 | 3-(2-quinolinylmethoxy)aniline; 3-(2-quinolinylmethoxy)phenylamine | C16H14N2O | 详情 | 详情 |