1-Acetyl-4-(4-hydoxyphenyl)piperazine; 1-[4-(4-hydroxyphenyl)-1-piperazinyl]-1-ethanone; N-Acetyl-4-(4-hydoxyphenyl)piperazine -Drug Synthesis Database

【结构式】

【分子编号】29119

【品名】1-Acetyl-4-(4-hydoxyphenyl)piperazine; 1-[4-(4-hydroxyphenyl)-1-piperazinyl]-1-ethanone; N-Acetyl-4-(4-hydoxyphenyl)piperazine

【CA登记号】67914-60-7

【分子式】C₁₂H₁₆N₂O₂

【分子量】220.27132

【元素组成】C 65.43% H 7.32% N 12.72% O 14.53%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(II)

The condensation of 2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-methanol methanesulfonate (I) with 1-(4-hydroxyphenyl)-4-acetylpiperazine (II) by means of NaH in DMSO gives the corresponding ether (III), which is desacetylated by means of NaOH in refluxing butanol to the substituted piperazine (IV). The condensation of (IV) with 4-chloronitrobenzene (V) by means of K2CO3 in hot DMSO yields the nitro compound (VI), which is reduced with H2 over Pt/C in ethylene glycol affording the substituted aniline (VII). The reaction of (VII) with phenyl chloroformate (VIII) by means of pyridine in CHCl3 gives the phenylcarbamate (IX).

参考文献中间体

合成目标

【1】 Van Cutsem, J.; Backx, L.J.J.; Heeres, J.; J. Antimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones. J Med Chem 1984, 27, 7, 894-900.
【2】 Castaner, J.; Serradell, M.N.; Fromtling, R.A.; Itraconazole. Drugs Fut 1985, 10, 4, 291.

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)	29118	[(2S,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl methanesulfonate; Cis-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl methanesulfonate	67914-86-7	C₁₄H₁₅Cl₂N₃O₅S	详情	详情
(II)	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
(III)	29120	1-[4-(4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)-1-piperazinyl]-1-ethanone		C₂₅H₂₇Cl₂N₅O₄	详情	详情
(IV)	29121	1-(4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)piperazine		C₂₃H₂₅Cl₂N₅O₃	详情	详情
(V)	13909	1-Chloro-4-nitrobenzene; p-Nitrochlorobenzene	100-00-5	C₆H₄ClNO₂	详情	详情
(VI)	29122	1-(4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)-4-(4-nitrophenyl)piperazine		C₂₉H₂₈Cl₂N₆O₅	详情	详情
(VII)	29123	4-[4-(4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)-1-piperazinyl]aniline		C₂₉H₃₀Cl₂N₆O₃	详情	详情
(VIII)	13580	1-[(Chlorocarbonyl)oxy]benzene; phenyl chloroformate	1885-14-9	C₇H₅ClO₂	详情	详情
(IX)	29124	phenyl 4-[4-(4-[[(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl)-1-piperazinyl]phenylcarbamate		C₃₆H₃₄Cl₂N₆O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IX)

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

Extended Information