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Triaconazole, Terconazole, R-42470, Terazol, Gyno-Terazol, Fungistat

曲康唑Chemical Name: cis-1-[4-[[2-(2,4-Dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-4-(1-methylethyl)piperazine
CAS No. 67915-31-5
项目整合开发状态: Launched-1984
项目研究机构: Cilag (Originator), Janssen-Cilag (Originator), Ortho-McNeil (Originator)
合成路线:The condensation of 2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(benzoyloxymethyl)-1,3-dioxolane (I) with triazole (II) by means of NaH in DMSO,followed by hydrolysis with NaOH in dioxane water gives 2-(2,4-dichlorophenyl)-2-(1H)-1,2,4-triazol-1-ylmethyl)-1,3-dioxolane-4-methanol (III),which is acylated with methanesulfonyl chloride in pyridine affording the corresponding 4-mesyloxymethyldioxolane (IV).Finally,this compound is condensed with 4-(4-isopropylpiperazin-1-yl)phenol (V) by means of NaH in hot DMSO.Compound (V) is obtained as follows: 4-(4-methoxyphenyl)piperazine (VI) is reductocondensed with acetone (A) by means of H2 over Pd/C giving 1-isopropyl-4-(4-methoxyphenyl)piperazine (VII),which is then demethylated with refluxing aqueous 48% HBr yielding (V)
📌 参考资料/链接:
参考文献标题:Novel 1-(1,3-dioxolan-2-ylmethyl)-1H-imidazoles
文献作者:Heeres,J.; Backx,L.J.J.; Mostmans,J.H.(Janssen Pharmaceutica NV)
参考来源:BE 0863382; FR 2378778; GB 1594859; JP 7895973; US 4144346; US 4223036

📄 详细内容


合成路线:The condensation of 2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(benzoyloxymethyl)-1,3-dioxolane (I) with triazole (II) by means of NaH in DMSO,followed by hydrolysis with NaOH in dioxane water gives 2-(2,4-dichlorophenyl)-2-(1H)-1,2,4-triazol-1-ylmethyl)-1,3-dioxolane-4-methanol (III),which is acylated with methanesulfonyl chloride in pyridine affording the corresponding 4-mesyloxymethyldioxolane (IV).Finally,this compound is condensed with 4-(4-isopropylpiperazin-1-yl)phenol (V) by means of NaH in hot DMSO.Compound (V) is obtained as follows: 4-(4-methoxyphenyl)piperazine (VI) is reductocondensed with acetone (A) by means of H2 over Pd/C giving 1-isopropyl-4-(4-methoxyphenyl)piperazine (VII),which is then demethylated with refluxing aqueous 48% HBr yielding (V)

参考文献标题:Terconazole
文献作者:Serradell,M.N.; Castar,J.; Fromtling,R.A.
参考来源:Drugs Fut 1984,9(7),529


合成路线:The condensation of 2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-(benzoyloxymethyl)-1,3-dioxolane (I) with triazole (II) by means of NaH in DMSO,followed by hydrolysis with NaOH in dioxane water gives 2-(2,4-dichlorophenyl)-2-(1H)-1,2,4-triazol-1-ylmethyl)-1,3-dioxolane-4-methanol (III),which is acylated with methanesulfonyl chloride in pyridine affording the corresponding 4-mesyloxymethyldioxolane (IV).Finally,this compound is condensed with 4-(4-isopropylpiperazin-1-yl)phenol (V) by means of NaH in hot DMSO.Compound (V) is obtained as follows: 4-(4-methoxyphenyl)piperazine (VI) is reductocondensed with acetone (A) by means of H2 over Pd/C giving 1-isopropyl-4-(4-methoxyphenyl)piperazine (VII),which is then demethylated with refluxing aqueous 48% HBr yielding (V)
参考文献标题:Antimycotic azoles.6.Synthesis and antifungal properties of terconazole,a novel triazole ketal
文献作者:Heeres,J.; Hendrickx,R.; Van Cutsem,J.
参考来源:J Med Chem 1983,26(4),611-613


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