• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】31863

【品名】(E)-1-cyclohexyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]-2-methyl-2-phenyl-3-buten-1-one

【CA登记号】

【 分 子 式 】C28H36N2O2

【 分 子 量 】432.60612

【元素组成】C 77.74% H 8.39% N 6.48% O 7.4%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

This compound has been obtained by three related ways: 1.- The Grignard condensation of ethyl cyclohexanecarboxylate (I) with benzylmagnesium bromide (II) in THF gives 1-cyclohexyl-2-phenylethanone (III), which is condensed with bromoacetaldehyde diethyl acetal (IV) by means of potassium tert-butoxide in DMSO to yield 4-cyclohexyl-4-oxo-3-phenylbutyraldehyde diethylacetal (V). The methylation of (V) by means of methyl iodide and potassium tert-butoxide in the same solvent affords 4-cyclohexyl-3-methyl-4-oxo-3-phenylbutyraldehyde diethylacetal (VI), which is treated with HCl in acetone to give the corresponding aldehyde (VII). The reductocondensation of (VII) with 1-(2-methoxyphenyl)piperazine (VIII) by means of sodium triacetoxyborohydride in dichloromethane/acetic acid yields 1-cyclohexyl-4-[4-(2-methoxyphenyl)piperazin-1-yl]-2-methyl-2-phenyl-1-butanone (X) as a racemic mixture, which is resolved by chiral chromatography over a Chiralpak AD column. 2.- The Grignard condensation of 2-phenylpropionaldehyde (XI) with cyclohexylmagnesium chloride (XII) in ethyl ether/THF gives 1-cyclohexyl-2-phenyl-1-propanol (XIII), which is oxidized with DMSO and P2O5 in dichloromethane yielding the corresponding ketone (XIV). The condensation of (XIV) with allyl bromide by means of potassium tert-butoxide in THF affords 1-cyclohexyl-2-methyl-2-phenyl-4-penten-1-one (XV), which is ozonolyzed with O3 in methanol catalyzed by a small amount of Sudan III affording the previously reported aldehyde (VII). 3.- The condensation of aldehyde (VII) with 1-(2-methoxyphenyl)piperazine (VIII) can also be performed in isopropyl acetate giving 1-cyclohexyl-4-[4-(2-methoxyphenyl)piperazin-1-yl]-2-methyl-2-phenyl-3-buten-1-one (IX), which is hydrogenated with H2 over Pd/C in isopropanol to afford the previously reported racemic mixture (X).

1 Xu, Y.C.; et al.; Synthesis and pharmacology of LY426965: A potent, selective orally active, and long-lasting 5-HT1A receptor antagonist. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 107.
2 Kohlman, D.T.; O'Toole, J.C.; Godfrey, A.G.; Xu, Y.-C.; Zhang, T.Y. (Eli Lilly and Company); Arylpiperazines having activity at the serotonin 1A receptor. EP 0924205; WO 9931077 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
11463 3-Bromo-1-propene; 3-Bromopropene;allyl bromide 106-95-6 C3H5Br 详情 详情
(I) 31858 ethyl cyclohexanecarboxylate 3289-28-9 C9H16O2 详情 详情
(II) 28308 benzyl(bromo)magnesium; benzylmagnesium bromide 1589-82-8 C7H7BrMg 详情 详情
(III) 31859 1-cyclohexyl-2-phenyl-1-ethanone C14H18O 详情 详情
(IV) 12113 2-Bromo-1-ethoxyethyl ethyl ether; 2-Bromo-1,1-diethoxyethane; Bromoacetaldehyde diethylacetal 2032-35-1 C6H13BrO2 详情 详情
(V) 31860 1-cyclohexyl-4,4-diethoxy-2-phenyl-1-butanone C20H30O3 详情 详情
(VI) 31861 1-cyclohexyl-4,4-diethoxy-2-methyl-2-phenyl-1-butanone C21H32O3 详情 详情
(VII) 31862 4-cyclohexyl-3-methyl-4-oxo-3-phenylbutanal C17H22O2 详情 详情
(VIII) 11882 1-(2-Methoxyphenyl)piperazine; Methyl 2-piperazinophenyl ether; 1-(2-Methoxyphenyl)-piperazine 35386-24-4 C11H16N2O 详情 详情
(IX) 31863 (E)-1-cyclohexyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]-2-methyl-2-phenyl-3-buten-1-one C28H36N2O2 详情 详情
(X) 31864 1-cyclohexyl-4-[4-(2-methoxyphenyl)-1-piperazinyl]-2-methyl-2-phenyl-1-butanone C28H38N2O2 详情 详情
(XI) 31865 hydratropaldehyde 93-53-8 C9H10O 详情 详情
(XII) 31866 chloro(cyclohexyl)magnesium C6H11ClMg 详情 详情
(XIII) 31867 1-cyclohexyl-2-phenyl-1-propanol C15H22O 详情 详情
(XIV) 31868 1-cyclohexyl-2-phenyl-1-propanone C15H20O 详情 详情
(XV) 31869 1-cyclohexyl-2-methyl-2-phenyl-4-penten-1-one C18H24O 详情 详情
Extended Information