Imazalil, Enilconazol, Enilconazole, R-23979, Imaverol, -Drug Synthesis Database

【结构式】

【药物名称】Imazalil, Enilconazol, Enilconazole, R-23979, Imaverol

【化学名称】1-[2-(2,4-Dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole

【CA登记号】58594-72-2

【分子式】C₁₄H₁₄Cl₂N₂O

【分子量】297.18648

【开发单位】Janssen (Originator)

【药理作用】Antifungal Agents, ANTIINFECTIVE THERAPY, Aromatase Inhibitors

合成路线1 合成路线2

合成路线1

The esterification of 2,4-dichloromandelic acid (I) with methanol and sulfuric acid gives the corresponding methyl ester (II), which by treatment with NH3 in methanol yields 2,4-dichloromandelamide (III). The alkylation of (III) with allyl chloride (IV) and NaH in THF affords 2-allyloxy-2-(2,4-dichlorophenyl)acetamide (V), which is hydrolyzed with refluxing aqueous HCl giving 2-allyloxy-2-(2,4-dichlorophenyl)acetic acid (VI). The reduction of (VI) with LiAlH4 in refluxing ether yields 2-allyloxy-2-(2,4-dichlorophenyl)ethanol (VII), which is esterified with methanesulfonyl chloride in pyridine to afford 2-allyloxy-2-(2,4-dichlorophenyl) ethanol methanesulfonate (VIII). Finally, this compound is condensed with 1H-imidazole (IX) in refluxing DMF.

参考文献中间体

【1】 GB 1522848 .
【2】 Serradell, M.N.; Blancafort, P.; Castaner, J.; de Angelis, L.; Imazalil. Drugs Fut 1982, 7, 4, 254.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	36400	2-(2,4-dichlorophenyl)-2-hydroxyacetic acid		C₈H₆Cl₂O₃	详情	详情
(II)	36401	methyl 2-(2,4-dichlorophenyl)-2-hydroxyacetate		C₉H₈Cl₂O₃	详情	详情
(III)	36402	2-(2,4-dichlorophenyl)-2-hydroxyacetamide		C₈H₇Cl₂NO₂	详情	详情
(IV)	13235	Allyl chloride; 3-Chloro-1-propene	107-05-1	C₃H₅Cl	详情	详情
(V)	36403	2-(allyloxy)-2-(2,4-dichlorophenyl)acetamide		C₁₁H₁₁Cl₂NO₂	详情	详情
(VI)	36404	2-(allyloxy)-2-(2,4-dichlorophenyl)acetic acid		C₁₁H₁₀Cl₂O₃	详情	详情
(VII)	36405	2-(allyloxy)-2-(2,4-dichlorophenyl)-1-ethanol		C₁₁H₁₂Cl₂O₂	详情	详情
(VIII)	36406	3-(allyloxy)-3-(2,4-dichlorophenyl)propyl methanesulfonate		C₁₃H₁₆Cl₂O₄S	详情	详情
(IX)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情

合成路线2

The bromination of 2,4-dichloroacetophenone (X) with Br2 in refluxing methanol gives 2,4-dichlorophenacyl bromide (XI), which is condensed with 1H-imidazole (IX) in methanol to yield 2,4-dichloro-alpha-(1-imidazolyl)acetophenone (XII). The reduction of (XII) with NaBH4 in refluxing methanol affords 1-(2,4-chlorophenyl)-2-(1-imidazolyl)ethanol (XIII), which is finally alkylated with allyl chloride (IV) and NaH in refluxing DMF.

参考文献中间体

【1】 Serradell, M.N.; Blancafort, P.; Castaner, J.; de Angelis, L.; Imazalil. Drugs Fut 1982, 7, 4, 254.
【2】 Godefroi, E.F.; Schuermans, J.L.; US 3658813 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	13235	Allyl chloride; 3-Chloro-1-propene	107-05-1	C₃H₅Cl	详情	详情
(IX)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情
(X)	36407	1-(2,4-dichlorophenyl)-1-ethanone; 2',4'-dichloroaetophenone	2234-16-4	C₈H₆Cl₂O	详情	详情
(XI)	36408	2-bromo-1-(2,4-dichlorophenyl)-1-ethanone		C₈H₅BrCl₂O	详情	详情
(XII)	32200	1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanone	46503-52-0	C₁₁H₈Cl₂N₂O	详情	详情
(XIII)	14550	1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)-1-ethanol; alpha-(2,4-Dichlorophenyl)-1H-imidazole-1-ethanol; 1-(2',4'-Dichlorophenyl)-2-(1-imidazolyl)ethanol	24155-42-8	C₁₁H₁₀Cl₂N₂O	详情	详情

Extended Information