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Ropinirole hydrochloride, SK&F-101468A, ReQuip

盐酸罗匹尼罗 罗匹尼罗 Chemical Name: 4-[2-(Dipropylamino)ethyl]-2,3-dihydro-1H-indol-2-one hydrochloride
CAS No. 91374-20-8, 91374-21-9 (free base)
项目整合开发状态: Launched-1996
项目研究机构: GlaxoSmithKline (Originator), SkyePharma (Formulation)
合成路线:The condensation of 2-(2-methyl-3-nitrophenyl)acetic acid (I) with dipropylamine (II) by means of refluxing SOCl2 gives the corresponding amide (III),which is reduced with borane/THF yielding the tertiary amine (IV).The condensation of (IV) with diethyl oxalate by means of sodium ethoxide in refluxing ethanol affords the pyruvate ester (V),which is treated with NaOH and H2O2 yielding the acetic acid derivative (VI).Finally,this compound is cyclyzed by hydrogenation with H2 over Pd/C in ethanol.
📌 参考资料/链接:
参考文献标题:4-Aminoalkyl-2(3H)-indolones
文献作者:Gallagher,G.Jr.(SmithKline Beecham Corp.)
参考来源:EP 0113964; ES 8600239; ES 8604143; US 4452808

📄 详细内容


合成路线:The bromination of 3,4-dihydro-1H-2-benzopyran (VII) with Br2 gives the 1-bromo derivative (VIII),which,without isolation,is treated with hot HBr yielding 2-(2-bromoethyl)benzaldehyde (IX).The condensation of (IX) with nitromethane in acidic medium affords the nitrostyrene (X),which is cyclized with treatment with FeCl3 and acetyl chloride giving 4-(2-bromoethyl)-3-chloroindolin-2-one (XI).The dechlorination of (XI) with NaH2PO2 over Pd/C yields 4-(2-bromoethyl)indolin-2-one (XII),which is finally condensed with dipropylamine (II).

合成路线:The reaction of 3,4-dihydro-1H-2-benzopyran (VII) with benzoyl chloride and ZnCl2 gives benzoic acid 2-[2-(chloromethyl)phenyl]ethyl ester (XIII),which is condensed with hexamethylenetetramine (XIV) yielding the amminium salt (XV).The hydrolysis of (XV) affords 2-(2-benzoyloxyethyl) benzaldehyde (XVI),which is condensed with nitromethane as before to give the nitrostyrene (XVII).The cyclization of (XVII) with FeCl3 and acetyl chloride as before yields 4-(2-benzoyloxyethyl)-3-chloroindolin-2-one (XVIII),which is dechlorinated with hydrazine and Pd/C to the indolinone (XIX).The hydrolysis of (XIX) with NaOH affords 4-(2-hydroxyethyl)indolin-2-one (XX),which is acylated with TsCl giving the tosylate (XXI).Finally,this compound is condensed with dipropylamine (II).
参考文献标题:Development of large-scale syntheses or ropinirole in the pursuit of a manufacturing process
文献作者:Hayler,J.D.; et al.
参考来源:Org Process Res Dev 1998,2(1),3


产品链接: CAS No. 91374-20-8››

产品链接: CAS No.91374-21-9››