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Mepindolol sulfate, SHE-222, Mepicor, Betagon, Corindolan

甲吲哚心安Chemical Name: 4-[2-Hydroxy-3-(isopropylamino)propoxy]-2-methylindole sulfate; 1-[(1-Methylethyl)amino]-3-(2-methyl-1H-indol-4-yloxy)-2-propanol sulfate
CAS No. 23694-81-7 (free base)
项目整合开发状态: Launched-1981
项目研究机构: Camillo Corvi (Originator), Schering AG (Originator)
合成路线:4-Benzyloxy-indole-2-carboxylic acid (I) is converted into the corresponding dimethylamide (III),via the corresponding acid chloride (II); the dimethylamide (III) is reduced with LiAlH4 to give 4-benzyloxy-2-dimethylaminomethyl-indole (IV),which is hydrogenated to 4-hydroxy-2-methyl-indole (V).The reaction of (V) with epichlorohydrin (A) in aqueous NaOH gives the crude epoxide which without isolation is treated with isopropylamine (B) in refluxing dioxane.

合成路线:4-Hydroxy-2-methyl-indole (IV) can be quaternized with MeI yielding the ammonium salt (VI),which by heating with aqueous NaCN in converted into 2-cyanomethyl-4-benzyloxyindole (VII).The hydrolysis of (VII) affords the corresponding acid (VIII),which is decarboxylated to 4-benzyloxy-2-methyl-indole (IX).Finally,this compound is hydrogenated to the previously obtained 4-hydroxy-2-methyl-indole (V).

合成路线:The reaction of 4-hydroxy-2-methyl-indole (V) with 1-(N-benzylisopropylamino)-3-chloro-2-propanol (D) by means of NaOH in refluxing aqueous dioxane yields the corresponding benzylamine (X),which is debenzylated by catalytic hydrogenation.The reaction of 4-hydroxy-2-methyl-indole (V) with epichlorohydrin (A) and benzylamine (B) gives 4-(3-benzylamino-2-hydroxypropoxy)-2-methyl-indole (XI),which is debenzylated by hydrogenolysis to 4-(3-amino-2-hydroxypropoxy)-2-methyl-indole (XII).The condensation of (XII) with refluxing acetone (C) affords the corresponding N-isopropylidene derivative (XIII),which is finally hydrogenated with H2 over Pd/C in methanol.
📌 参考资料/链接:
参考文献标题:Mepindolol
文献作者:Weetman,D.F.; Castar,J.
参考来源:Drugs Fut 1978,3(5),381

📄 详细内容


合成路线:4-Benzyloxy-indole-2-carboxylic acid (I) is converted into the corresponding dimethylamide (III),via the corresponding acid chloride (II); the dimethylamide (III) is reduced with LiAlH4 to give 4-benzyloxy-2-dimethylaminomethyl-indole (IV),which is hydrogenated to 4-hydroxy-2-methyl-indole (V).The reaction of (V) with epichlorohydrin (A) in aqueous NaOH gives the crude epoxide which without isolation is treated with isopropylamine (B) in refluxing dioxane.

合成路线:4-Hydroxy-2-methyl-indole (IV) can be quaternized with MeI yielding the ammonium salt (VI),which by heating with aqueous NaCN in converted into 2-cyanomethyl-4-benzyloxyindole (VII).The hydrolysis of (VII) affords the corresponding acid (VIII),which is decarboxylated to 4-benzyloxy-2-methyl-indole (IX).Finally,this compound is hydrogenated to the previously obtained 4-hydroxy-2-methyl-indole (V).

参考文献标题:Verfahren zur Herstellung neuer Indolderivate
文献作者:Troxler,F.; Hofmann,A.
参考来源:AT 316542B; CH 502337


合成路线:The reaction of 4-hydroxy-2-methyl-indole (V) with 1-(N-benzylisopropylamino)-3-chloro-2-propanol (D) by means of NaOH in refluxing aqueous dioxane yields the corresponding benzylamine (X),which is debenzylated by catalytic hydrogenation.The reaction of 4-hydroxy-2-methyl-indole (V) with epichlorohydrin (A) and benzylamine (B) gives 4-(3-benzylamino-2-hydroxypropoxy)-2-methyl-indole (XI),which is debenzylated by hydrogenolysis to 4-(3-amino-2-hydroxypropoxy)-2-methyl-indole (XII).The condensation of (XII) with refluxing acetone (C) affords the corresponding N-isopropylidene derivative (XIII),which is finally hydrogenated with H2 over Pd/C in methanol.

参考文献标题:Verfahren zur Herstellung neuer Indolderivate
文献作者:Troxler,F.
参考来源:CH 472404; ES 337457


合成路线:4-Benzyloxy-indole-2-carboxylic acid (I) is converted into the corresponding dimethylamide (III),via the corresponding acid chloride (II); the dimethylamide (III) is reduced with LiAlH4 to give 4-benzyloxy-2-dimethylaminomethyl-indole (IV),which is hydrogenated to 4-hydroxy-2-methyl-indole (V).The reaction of (V) with epichlorohydrin (A) in aqueous NaOH gives the crude epoxide which without isolation is treated with isopropylamine (B) in refluxing dioxane.

参考文献标题:Verfahren zur Herstellung neuer Indolderivate
文献作者:Troxler,F.; Hofmann,A.
参考来源:CH 543505


合成路线:The reaction of 4-hydroxy-2-methyl-indole (V) with 1-(N-benzylisopropylamino)-3-chloro-2-propanol (D) by means of NaOH in refluxing aqueous dioxane yields the corresponding benzylamine (X),which is debenzylated by catalytic hydrogenation.The reaction of 4-hydroxy-2-methyl-indole (V) with epichlorohydrin (A) and benzylamine (B) gives 4-(3-benzylamino-2-hydroxypropoxy)-2-methyl-indole (XI),which is debenzylated by hydrogenolysis to 4-(3-amino-2-hydroxypropoxy)-2-methyl-indole (XII).The condensation of (XII) with refluxing acetone (C) affords the corresponding N-isopropylidene derivative (XIII),which is finally hydrogenated with H2 over Pd/C in methanol.

参考文献标题:Verfahren zur Herstellung von neuem 4-(2-Hydroxy-3-isopropylaminopropoxy)-2-methylindol und seiner S鋟readditionssalze Indolderivate
文献作者:Troxler,F.
参考来源:AT 317199


合成路线:The reaction of 4-hydroxy-2-methyl-indole (V) with 1-(N-benzylisopropylamino)-3-chloro-2-propanol (D) by means of NaOH in refluxing aqueous dioxane yields the corresponding benzylamine (X),which is debenzylated by catalytic hydrogenation.The reaction of 4-hydroxy-2-methyl-indole (V) with epichlorohydrin (A) and benzylamine (B) gives 4-(3-benzylamino-2-hydroxypropoxy)-2-methyl-indole (XI),which is debenzylated by hydrogenolysis to 4-(3-amino-2-hydroxypropoxy)-2-methyl-indole (XII).The condensation of (XII) with refluxing acetone (C) affords the corresponding N-isopropylidene derivative (XIII),which is finally hydrogenated with H2 over Pd/C in methanol.

参考文献标题:Verfahren zur Herstellung neuer Indolderivate
文献作者:Troxler,F.
参考来源:CH 469002; ES 337458


合成路线:4-Benzyloxy-indole-2-carboxylic acid (I) is converted into the corresponding dimethylamide (III),via the corresponding acid chloride (II); the dimethylamide (III) is reduced with LiAlH4 to give 4-benzyloxy-2-dimethylaminomethyl-indole (IV),which is hydrogenated to 4-hydroxy-2-methyl-indole (V).The reaction of (V) with epichlorohydrin (A) in aqueous NaOH gives the crude epoxide which without isolation is treated with isopropylamine (B) in refluxing dioxane.

合成路线:The reaction of 4-hydroxy-2-methyl-indole (V) with 1-(N-benzylisopropylamino)-3-chloro-2-propanol (D) by means of NaOH in refluxing aqueous dioxane yields the corresponding benzylamine (X),which is debenzylated by catalytic hydrogenation.The reaction of 4-hydroxy-2-methyl-indole (V) with epichlorohydrin (A) and benzylamine (B) gives 4-(3-benzylamino-2-hydroxypropoxy)-2-methyl-indole (XI),which is debenzylated by hydrogenolysis to 4-(3-amino-2-hydroxypropoxy)-2-methyl-indole (XII).The condensation of (XII) with refluxing acetone (C) affords the corresponding N-isopropylidene derivative (XIII),which is finally hydrogenated with H2 over Pd/C in methanol.
参考文献标题:Synthetic indoles.10.Chemistry of 4-hydroxy-indoles
文献作者:Seemann,F.; et al.
参考来源:Helv Chim Acta 1971,54(8),2411-19


产品链接: CAS No. 23694-81-7››