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Alminoprofen, EB-382, Minalfene

阿明洛芬Chemical Name: p-[(2-Methylallyl)amino]hydratropic acid; 2-[4-(2-Methylallylamino)phenyl]propionic acid; alpha-Methyl-4-[(2-methyl-2-propenyl)amino]benzeneacetic acid
CAS No. 39718-89-3
项目整合开发状态: Launched-1983
项目研究机构: Bouchara (Not Determined), Morishita (Not Determined), UCB Japan (Not Determined)
合成路线:The reaction of 4-nitrophenylacetic acid (I) with formaldehyde and dimethylamine in water gives 2-(4-nitrophenyl)-3-(dimethylamino)propionic acid (II),which by treatment with refluxing concentrated HCl is converted into 2-(4-nitrophenyl)acrylic acid (III).The esterification of (III) with methanol and p-toluenesulfonic acid yields the corresponding methyl ester (IV),which is reduced with H2 over Pd/C in ethanol to afford methyl 2-(4-aminophenyl)propionate (V).The alkylation of (V) with 2-methylallyl chloride (VI) by means of pyridine in refluxing ethanol gives methyl 2-[4-(2-methylallylamino)phenyl]propionate (VII),which is finally hydrolyzed with NaOH in refluxing methanol.
📌 参考资料/链接:
参考文献标题:Nouveau procede de preparation de derives de l'acide phenylacetique
文献作者:Bouchara,E.(Laboratoires du Dr.E.Bouchara)
参考来源:FR 2289180

📄 详细内容


合成路线:The malonic synthesis of 4-nitrochlorobenzene (VIII) with sodium diethyl methylmalonate (IX) (prepared with the corresponding malonic ester and NaH) in hot DMF gives diethyl (4-nitrophenyl)methylmalonate (X),which is reduced with H2 over Pd/C as before yielding diethyl (4-aminophenyl)methylmalonate (XI).The alkylation of (XI) with (VI) by means of NaHCO3 in refluxing ethanol affords diethyl [4-(2-methylallyl)aminophenyl]methylmalonate (XII),which is treated with sodium ethoxide in refluxing ethanol to yield ethyl 2-(4-[2-methylallylamino)phenyl]propionate (XIV).Finally,this compound is hydrolyzed with NaOH in refluxing ethanol.Partial hydrolysis of (XII) with NaOH in refluxing ethanol gives 2-[4-(2-methylallylamino)phenyl]methylmalonic acid (XIII),which is finally decarboxylated by treatment with refluxing aqueous HCl.The simultaneous hydrolysis and decarboxylation of (XII) with NaOH in refluxing ethanol also gives the title product.

合成路线:The reaction of 4-nitrophenylacetic acid (I) with formaldehyde and dimethylamine in water gives 2-(4-nitrophenyl)-3-(dimethylamino)propionic acid (II),which by treatment with refluxing concentrated HCl is converted into 2-(4-nitrophenyl)acrylic acid (III).The esterification of (III) with methanol and p-toluenesulfonic acid yields the corresponding methyl ester (IV),which is reduced with H2 over Pd/C in ethanol to afford methyl 2-(4-aminophenyl)propionate (V).The alkylation of (V) with 2-methylallyl chloride (VI) by means of pyridine in refluxing ethanol gives methyl 2-[4-(2-methylallylamino)phenyl]propionate (VII),which is finally hydrolyzed with NaOH in refluxing methanol.

参考文献标题:Alminoprofen
文献作者:Serradell,M.N.; Castar,J.
参考来源:Drugs Fut 1984,9(3),165


合成路线:The malonic synthesis of 4-nitrochlorobenzene (VIII) with sodium diethyl methylmalonate (IX) (prepared with the corresponding malonic ester and NaH) in hot DMF gives diethyl (4-nitrophenyl)methylmalonate (X),which is reduced with H2 over Pd/C as before yielding diethyl (4-aminophenyl)methylmalonate (XI).The alkylation of (XI) with (VI) by means of NaHCO3 in refluxing ethanol affords diethyl [4-(2-methylallyl)aminophenyl]methylmalonate (XII),which is treated with sodium ethoxide in refluxing ethanol to yield ethyl 2-(4-[2-methylallylamino)phenyl]propionate (XIV).Finally,this compound is hydrolyzed with NaOH in refluxing ethanol.Partial hydrolysis of (XII) with NaOH in refluxing ethanol gives 2-[4-(2-methylallylamino)phenyl]methylmalonic acid (XIII),which is finally decarboxylated by treatment with refluxing aqueous HCl.The simultaneous hydrolysis and decarboxylation of (XII) with NaOH in refluxing ethanol also gives the title product.

合成路线:The reaction of 4-nitrophenylacetic acid (I) with formaldehyde and dimethylamine in water gives 2-(4-nitrophenyl)-3-(dimethylamino)propionic acid (II),which by treatment with refluxing concentrated HCl is converted into 2-(4-nitrophenyl)acrylic acid (III).The esterification of (III) with methanol and p-toluenesulfonic acid yields the corresponding methyl ester (IV),which is reduced with H2 over Pd/C in ethanol to afford methyl 2-(4-aminophenyl)propionate (V).The alkylation of (V) with 2-methylallyl chloride (VI) by means of pyridine in refluxing ethanol gives methyl 2-[4-(2-methylallylamino)phenyl]propionate (VII),which is finally hydrolyzed with NaOH in refluxing methanol.
参考文献标题:Synthesis of some analgesic and antiinflammatory 4-aminophenylacetic and 4-aminophenylacetic and 2-(4-aminophenyl)propionic acid derivatives
文献作者:Dumaitre,B.; et al.
参考来源:Eur J Med Chem - Chim Ther 1979,14(3),207-214


产品链接: CAS No. 39718-89-3››