2-bromo-1-(2,4-dichlorophenyl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】36408

【品名】2-bromo-1-(2,4-dichlorophenyl)-1-ethanone

【CA登记号】

【分子式】C₈H₅BrCl₂O

【分子量】267.9365

【元素组成】C 35.86% H 1.88% Br 29.82% Cl 26.46% O 5.97%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XI)

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

合成目标

【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

合成路线2

该中间体在本合成路线中的序号：(I)

The cyclization of 2,4-dichlorophenacyl bromide (I) with glycerol (II) gives cis-2-(2,4-dichlorophenyl)-2-bromomethyl-4-hydroxymethyl-1,3-dioxolane (III), which is then benzoylated with benzoyl chloride (A) yielding cis-2-(2,4-dichlorophenyl)-2-bromomethyl-4-benzoyloxymethyl-1,3-dioxolane (IV). The condensation of (IV) with 1H-imidazole (V) affords cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-4-benzoyloxymethyl-1,3-dioxolane (VI), which is then debenzoylated in basic medium giving cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-4-hydroxymethyl-1,3-dioxolane (VII). The reaction of (VII) with methanesulfonyl chloride (B) yields cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-ylmethyl methanesulfonate (VIII). Finally, this compound is condensed with 1-acetyl-4-(4-hydroxyphenyl)piperazine (IX) by means of NaH in benzene - DMSO. Compound (IX) is obtained by reaction of 4-(1-piperazinyl)phenol dihydrobromide (X) with acetic anhydride by means of K2CO3 in refluxing acetic acid.

参考文献中间体

合成目标

【1】 Heeres, J.; et al.; DE 2804096 .
【2】 Blancafort, P.; Sweetman, A.J.; Castaner, J.; Serradell, M.N.; Ketoconazole. Drugs Fut 1979, 4, 7, 496.
【3】 Backx, L.J.J.; Mostmans, J.H.; Heeres, J. (Janssen Pharmaceutica NV); 1-(1,3-Dioxolan-2-ylmethyl)-1H-imidazoles. US 4335125 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	10463	Benzoyl chloride	98-88-4	C₇H₅ClO	详情	详情
(B)	13467	Methanesulfonyl chloride;Mesyl chloride;Methylsulfonyl chloride;Methanesulfonic acid chloride;Methanesulfonyl chloride;Methanesulphonyl chloride	124-63-0	CH₃ClO₂S	详情	详情
(I)	36408	2-bromo-1-(2,4-dichlorophenyl)-1-ethanone		C₈H₅BrCl₂O	详情	详情
(II)	13289	Glycerine; Glycerin; Glycerol	56-81-5	C₃H₈O₃	详情	详情
(III)	39602	[(2S,4R)-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methanol		C₁₁H₁₁BrCl₂O₃	详情	详情
(IV)	30485	[(2S,4S)-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methyl benzoate; cis-2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolan-4-yl]methyl benzoate		C₁₈H₁₅BrCl₂O₄	详情	详情
(V)	10255	Imidazole; 1H-Imidazole	288-32-4	C₃H₄N₂	详情	详情
(VI)	39603	[(2S,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl benzoate		C₂₁H₁₈Cl₂N₂O₄	详情	详情
(VII)	39604	[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methanol	170210-50-1	C₁₄H₁₄Cl₂N₂O₃	详情	详情
(VIII)	39605	[(2S,4S)-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl methanesulfonate; cis-2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl methanesulfonate		C₁₅H₁₆Cl₂N₂O₅S	详情	详情
(IX)	29119	1-Acetyl-4-(4-hydoxyphenyl)piperazine; 1-[4-(4-hydroxyphenyl)-1-piperazinyl]-1-ethanone; N-Acetyl-4-(4-hydoxyphenyl)piperazine	67914-60-7	C₁₂H₁₆N₂O₂	详情	详情
(X)	39606	4-(1-piperazinyl)phenol; 1-(4-Hydroxyphenyl)piperazine	56621-48-8	C₁₀H₁₄N₂O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

This compound has been obtained by two similar ways: The enantiocontrolled reduction of 2,4-dichlorophenacyl bromide (I) with BH3/THF and a chiral oxazaborole catalyst gives 1(S)-(2,4-dichlorophenyl)-2-bromoethanol (II), which is treated with Ms-Cl and TEA in dichloromethane to yield the corresponding mesylate (III). Finally, this compound is cyclized with 2-(1-imidazolyl)-3,3-disulfanylacrylonitrile (VI) by means of KOH in DMSO. Alternatively, 1(S)-(2,4-dichlorophenyl)ethane-1,2-diol (VII) is treated with Ms-Cl and TEA in dichloromethane to give the corresponding dimesylate (VIII), which is condensed with the acrylonitrile (VI) with KOH as before. The intermediate acrylonitrile (VI) has been obtained by condensation of 2-(1-imidazolyl)acetonitrile (IV) with CS2 (V) by means of KOH in DMSO.

参考文献中间体

合成目标

【1】 Kodama, H.; Niwano, Y.; Kanai, K.; Yoshida, M. (Nihon Nohyaku Co., Ltd.); Antifungal agent, cpd. therefor, process for producing the same. JP 1997100279; JP 1998158168; US 5900488; WO 9702821 .

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)	36408	2-bromo-1-(2,4-dichlorophenyl)-1-ethanone		C₈H₅BrCl₂O	详情	详情
(II)	53962	(1S)-2-bromo-1-(2,4-dichlorophenyl)-1-ethanol	n/a	C₈H₇BrCl₂O	详情	详情
(III)	53963	(1S)-2-bromo-1-(2,4-dichlorophenyl)ethyl methanesulfonate	n/a	C₉H₉BrCl₂O₃S	详情	详情
(IV)	13535	2-(1H-Imidazol-1-yl)acetonitrile		C₅H₅N₃	详情	详情
(V)	53967	Alcohol of sulfur; Carbon bisulfuret; Carbon disulfide; Carbon sulfide; Dithiocarbonic anhydride; Methyl disulfide; Sulfocarbonic anhydride	75-15-0	CS₂	详情	详情
(VI)	53964	2-(1H-imidazol-1-yl)-3,3-disulfanylacrylonitrile	n/a	C₆H₅N₃S₂	详情	详情
(VII)	53965	(1S)-1-(2,4-dichlorophenyl)-1,2-ethanediol	n/a	C₈H₈Cl₂O₂	详情	详情
(VIII)	53966	(1S)-1-(2,4-dichlorophenyl)-2-[(methylsulfonyl)oxy]ethyl methanesulfonate	n/a	C₁₀H₁₂Cl₂O₆S₂	详情	详情

Extended Information