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Tropesin, VUFB-12018, Repanidal

Chemical Name: d,l-2-Phenyl-3-[1-(4-chlorobenzoyl)-5-methoxy-2-methylindol-3-ylacetoxy]propionic acid; (?-(4-Chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-acetic acid 2-carboxy-2-phenylethyl ester
CAS No. 65189-78-8, 65828-79-7 (undefined stereoch.)
项目整合开发状态: Launched-1989
项目研究机构: Res. Inst. Pharmacy Biochemistry (VUFB) (Originator), SPOFA (Originator)
合成路线:1) The reaction of N1-(4-chlorobenzoyl)-N1-(4-methoxyphenyl)hydrazine (I) [the starting material for the synthesis of indomethacin],with d,l-(2-carboxyethyl-2-phenyl)-4-oxopentanoate (II) under the conditions of Fischer indole synthesis by means of 100% phosphoric acid in toluene at 100 C.d,l-(2-Carboxyethyl-2-phenyl)-4-oxopentanoate (II) is obtained hy treatment of d,l-tropic acid with levulinic acid chloride.

合成路线:2) The reaction of indomethacin (III) with thionyl chloride in hot toluene gives the corresponding acyl chloride (IV),which is then condensed with tropic acid (V) in refluxing toluene containing pyridine to afford title compound.

合成路线:3) The treatment of indomethacin (III) with 1,1'-carbonyldiimidazole (A) at room temperature in dichloromethane affords the imidazolide (IVa),which is reacted with tropic acid (V) under the same mild conditions to afford title compound.
📌 参考资料/链接:
参考文献标题:2-Phenyl-2-carboxyethyl 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetate and process for preparation thereof
文献作者:Nemecek,O.; Fisnerova,L.; Grimova,J.; Roubal,Z.(SPOFA - United Pharmaceutical Works)
参考来源:US 4136194

📄 详细内容


合成路线:1) The reaction of N1-(4-chlorobenzoyl)-N1-(4-methoxyphenyl)hydrazine (I) [the starting material for the synthesis of indomethacin],with d,l-(2-carboxyethyl-2-phenyl)-4-oxopentanoate (II) under the conditions of Fischer indole synthesis by means of 100% phosphoric acid in toluene at 100 C.d,l-(2-Carboxyethyl-2-phenyl)-4-oxopentanoate (II) is obtained hy treatment of d,l-tropic acid with levulinic acid chloride.

参考文献标题:N-acyl-phenylhydrazine sulfamic acids and salts thereof
文献作者:Sletzinger,M.; Chemerda,J.M.; Summit,G.G.(Merck & Co.,Inc.)
参考来源:DE 1643462; DE 1643463; DE 1768016; DE 1770022; FR 1540724; FR 1540725; GB 1161270; GB 1173986


合成路线:1) The reaction of N1-(4-chlorobenzoyl)-N1-(4-methoxyphenyl)hydrazine (I) [the starting material for the synthesis of indomethacin],with d,l-(2-carboxyethyl-2-phenyl)-4-oxopentanoate (II) under the conditions of Fischer indole synthesis by means of 100% phosphoric acid in toluene at 100 C.d,l-(2-Carboxyethyl-2-phenyl)-4-oxopentanoate (II) is obtained hy treatment of d,l-tropic acid with levulinic acid chloride.

参考文献标题:Method of producing 2-phenyl-2-carboxyethyl ester of levulinic acid
文献作者:Fisnerova,L.; Nemecek,O.
参考来源:CS 194283


合成路线:2) By condensation of 1-(3-chloro 2 hydroxypropyl)-2-nitroimidazole (III) with piperidine (IV) in refluxing methanol.

合成路线:3) By condensation of 1-(2,3-epoxypropyl)-2 nitroimidazole (V) with (IV) in refluxing ethanol.

合成路线:1) The reaction of N1-(4-chlorobenzoyl)-N1-(4-methoxyphenyl)hydrazine (I) [the starting material for the synthesis of indomethacin],with d,l-(2-carboxyethyl-2-phenyl)-4-oxopentanoate (II) under the conditions of Fischer indole synthesis by means of 100% phosphoric acid in toluene at 100 C.d,l-(2-Carboxyethyl-2-phenyl)-4-oxopentanoate (II) is obtained hy treatment of d,l-tropic acid with levulinic acid chloride.

参考文献标题:Method of producing 2-phenyl-2-carboxyethyl ester of 1-p-chlorobenzoyl-5-methoxy-2-methyl-3-indolyl acetic acid
文献作者:Fisnerova,L.; Nemecek,O.
参考来源:CS 194284


合成路线:1) The reaction of N1-(4-chlorobenzoyl)-N1-(4-methoxyphenyl)hydrazine (I) [the starting material for the synthesis of indomethacin],with d,l-(2-carboxyethyl-2-phenyl)-4-oxopentanoate (II) under the conditions of Fischer indole synthesis by means of 100% phosphoric acid in toluene at 100 C.d,l-(2-Carboxyethyl-2-phenyl)-4-oxopentanoate (II) is obtained hy treatment of d,l-tropic acid with levulinic acid chloride.

合成路线:2) The reaction of indomethacin (III) with thionyl chloride in hot toluene gives the corresponding acyl chloride (IV),which is then condensed with tropic acid (V) in refluxing toluene containing pyridine to afford title compound.

合成路线:3) The treatment of indomethacin (III) with 1,1'-carbonyldiimidazole (A) at room temperature in dichloromethane affords the imidazolide (IVa),which is reacted with tropic acid (V) under the same mild conditions to afford title compound.

参考文献标题:Tropesin
文献作者:Fisnerov? L.
参考来源:Drugs Fut 1986,11(9),779


合成路线:2) The reaction of indomethacin (III) with thionyl chloride in hot toluene gives the corresponding acyl chloride (IV),which is then condensed with tropic acid (V) in refluxing toluene containing pyridine to afford title compound.

合成路线:3) The treatment of indomethacin (III) with 1,1'-carbonyldiimidazole (A) at room temperature in dichloromethane affords the imidazolide (IVa),which is reacted with tropic acid (V) under the same mild conditions to afford title compound.

参考文献标题:Pharmacologically interesting indomethacin derivatives
文献作者:Fisnerova,L.; et al.
参考来源:Cesk Farm 1977,26(6),227-31


合成路线:1) The reaction of N1-(4-chlorobenzoyl)-N1-(4-methoxyphenyl)hydrazine (I) [the starting material for the synthesis of indomethacin],with d,l-(2-carboxyethyl-2-phenyl)-4-oxopentanoate (II) under the conditions of Fischer indole synthesis by means of 100% phosphoric acid in toluene at 100 C.d,l-(2-Carboxyethyl-2-phenyl)-4-oxopentanoate (II) is obtained hy treatment of d,l-tropic acid with levulinic acid chloride.
参考文献标题:Pharmacologically interesting derivatives of indomethacin
文献作者:Grimova,J.; Rabek,V.; Roubal,Z.; Fisnerov? L.
参考来源:Cesk Farm 1977,26277


产品链接: CAS No. 65189-78-8››

产品链接: CAS No.65828-79-7››