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Losulazine hydrochloride, U-54669F

罗苏拉净 洛硫嗪 Chemical Name: 1-[(4-Fluorophenyl)sulfonyl]-4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine hydrochloride
CAS No. 81435-67-8, 72141-57-2 (free base, anhydrous)
项目整合开发状态: Phase III
项目研究机构: Pfizer (Originator)
合成路线:3) The third synthesis starts with acylation of piperazine (V) with 4-nitrobenzoyl chloride (VIII) to the corresponding amide (IX),which is sulfonated with 4-fluorobenzenesulfonyl chloride (VII) yielding 1-(4-nitrobenzoyl)-4-(4-fluorobenzenesulfonyl)piperazine (X).The reduction of the nitro group of (X) affords the corresponding amino derivative (XI) [also obtained by previous reduction of (IX) to 1-(4-aminobenzoyl)piperazine (XII) and sulfonation with (VII) as before].Finally,(XI) is condensed with quinoline (I) to give U-54669 F.This is an economically better method since the most expensive product [quinoline (I)] is used in the last step of the synthesis,so obtaining better yields.
📌 参考资料/链接:
参考文献标题:Process for 4-amino quinolines
文献作者:McCall,J.M.(Pharmacia Corp.)
参考来源:EP 0215902; JP 1987502339; WO 8605489

📄 详细内容


合成路线:The earlier synthesis starts with the reaction of 4-chloro-7-(trifluoromethyl)quinoline (I) with 4-aminobenzoic acid (II) in ethanol-HCl giving 4-(4-carboxyphenylamino)-7-(trifluoromethyl)quinoline (III),which is converted to its acyl chloride (IV) by treatment with SOCl2.The reaction of (IV) with piperazine (V) yields 1-[4-[7-(trifluoromethyl)quinolin-4-ylamino]benzoyl]piperazine (VI),which is finally acylated with 4-fluorobenzenesulfonyl chloride (VII) to give U-54669 F.However,this method is not economically efficient,since the most expensive compound [quinoline (I)] is already used in the first step of the synthesis.

合成路线:The condensation of 4-nitrobenzoyl chloride (I) with piperazine (II) in water by means of KOH gives 4-nitrobenzoylpiperazine (III),which is reduced with H2 over Pd/C in methanol yielding 4-aminobenzoyl piperazine (IV).The condensation of (IV) with 4-chloro-7-trifluoromethylquinoline (V) by means of HCl in refluxing ethanol affords 4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine (VI),which is finally acylated with 4-fluorobenzenesulfonyl chloride (VII) by means of triethylamine in THF.

参考文献标题:Aminoquinolines
文献作者:McCall,J.M.(Pharmacia Corp.)
参考来源:GB 2021567


合成路线:The condensation of 4-nitrobenzoyl chloride (I) with piperazine (II) in water by means of KOH gives 4-nitrobenzoylpiperazine (III),which is reduced with H2 over Pd/C in methanol yielding 4-aminobenzoyl piperazine (IV).The condensation of (IV) with 4-chloro-7-trifluoromethylquinoline (V) by means of HCl in refluxing ethanol affords 4-[4-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoyl]piperazine (VI),which is finally acylated with 4-fluorobenzenesulfonyl chloride (VII) by means of triethylamine in THF.
参考文献标题:U-54669-F
文献作者:Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1984,9(1),36


产品链接: CAS No. 81435-67-8››

产品链接: CAS No.72141-57-2››