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Sertindole, S-1991, Lu-23-174(maleate), Serdolect, Serlect

舍吲哚Chemical Name: 5-Chloro-1-(4-fluorophenyl)-3-[1-(2-oxoimidazolidin-1-ylethyl)piperidin-4-yl]-1H-indole; 1-[2-[4-[5-Chloro-1-(4-fluorophenyl)-1H-indol-3-yl]piperidin-1-yl]ethyl]imidazolidin-2-one
CAS No. 106516-24-9, 106516-25-0 (monomaleate)
项目整合开发状态: Registered-2001
项目研究机构: Lundbeck (Originator), Abbott (Licensee), Shionogi (Licensee)
合成路线:Acid-catalyzed condensation of 4-piperidone hydrate hydrochloride (IX) with indole (IV) produced the tetrahydropyridyl indole (X).This was alkylated with 1-(2-chloroethyl)imidazolinone (XII),(prepared by chlorination of the corresponding hydroxyethyl imidazolinone (XI)) to afford the N-substituted tetrahydropyridine (XIII).The target piperidine derivative was then obtained by catalytic hydrogenation of tetrahydropyridine (XIII).
📌 参考资料/链接:
参考文献标题:Heterocyclic cpds.
文献作者:Perregaard,J.K.(H.Lundbeck A/S)
参考来源:AU 8655901; EP 0200322; ES 8707499; JP 1986236764; US 4710500

📄 详细内容


合成路线:In an alternative method,Ullmann arylation of potassium N-(4-fluorophenyl)glycinate (VI) with potassium 2,5-dichlorobenzoate (V) afforded the N,N-diaryl glycine (VII).Cyclization of diacid (VII) in refluxing Ac2O produced the 3-acetoxy indole (VIII).This was then reduced to indole (IV) with NaBH4 in refluxing EtOH.

合成路线:Acid-catalyzed condensation of 4-piperidone hydrate hydrochloride (IX) with indole (IV) produced the tetrahydropyridyl indole (X).This was alkylated with 1-(2-chloroethyl)imidazolinone (XII),(prepared by chlorination of the corresponding hydroxyethyl imidazolinone (XI)) to afford the N-substituted tetrahydropyridine (XIII).The target piperidine derivative was then obtained by catalytic hydrogenation of tetrahydropyridine (XIII).

参考文献标题:Piperidyl-substd.indoles
文献作者:Perregaard,J.K.; Costall,B.(H.Lundbeck A/S)
参考来源:EP 0533824; JP 1993509080; US 5439922; WO 9200070


合成路线:In an alternative method,Ullmann arylation of potassium N-(4-fluorophenyl)glycinate (VI) with potassium 2,5-dichlorobenzoate (V) afforded the N,N-diaryl glycine (VII).Cyclization of diacid (VII) in refluxing Ac2O produced the 3-acetoxy indole (VIII).This was then reduced to indole (IV) with NaBH4 in refluxing EtOH.

合成路线:Acid-catalyzed condensation of 4-piperidone hydrate hydrochloride (IX) with indole (IV) produced the tetrahydropyridyl indole (X).This was alkylated with 1-(2-chloroethyl)imidazolinone (XII),(prepared by chlorination of the corresponding hydroxyethyl imidazolinone (XI)) to afford the N-substituted tetrahydropyridine (XIII).The target piperidine derivative was then obtained by catalytic hydrogenation of tetrahydropyridine (XIII).

参考文献标题:Method of manufacturing sertindole
文献作者:Bech Sommer,M.(H.Lundbeck A/S)
参考来源:WO 9851685


合成路线:Decarbomethoxylation of the known 3-hydroxyindole-2-carboxylate (I) in the presence of magnesium chloride in NMP at 160 C afforded indolinone (II),which was subsequently reduced with NaBH4 to the 3-hydroxy indoline (III).Dehydration of (III) by means of trifluoroacetic acid furnished indole (IV).

合成路线:In an alternative method,Ullmann arylation of potassium N-(4-fluorophenyl)glycinate (VI) with potassium 2,5-dichlorobenzoate (V) afforded the N,N-diaryl glycine (VII).Cyclization of diacid (VII) in refluxing Ac2O produced the 3-acetoxy indole (VIII).This was then reduced to indole (IV) with NaBH4 in refluxing EtOH.

合成路线:Acid-catalyzed condensation of 4-piperidone hydrate hydrochloride (IX) with indole (IV) produced the tetrahydropyridyl indole (X).This was alkylated with 1-(2-chloroethyl)imidazolinone (XII),(prepared by chlorination of the corresponding hydroxyethyl imidazolinone (XI)) to afford the N-substituted tetrahydropyridine (XIII).The target piperidine derivative was then obtained by catalytic hydrogenation of tetrahydropyridine (XIII).
参考文献标题:Noncataleptogenic,centrally acting dopamine D-2 and serotonin 5-HT2 antagonists within a series of 3-substituted 1-(4-fluorophenyl)-1H-indoles
文献作者:Perregaard,J.; Arnt,J.; Bogeso,K.P.; Hyttel,J.; S醤chez,C.
参考来源:J Med Chem 1992,35(6),1092


产品链接: CAS No. 106516-24-9››

产品链接: CAS No.106516-25-0››