1-(4-fluorophenyl)-2-(4-pyridinyl)-1,2-ethanedione -Drug Synthesis Database

【结构式】

【分子编号】37913

【品名】1-(4-fluorophenyl)-2-(4-pyridinyl)-1,2-ethanedione

【CA登记号】

【分子式】C₁₃H₈FNO₂

【分子量】229.2104632

【元素组成】C 68.12% H 3.52% F 8.29% N 6.11% O 13.96%

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：(VI)

4-[(tert-Butyldimethylsilyloxy)methyl]pyridine (II) was prepared by silylation of 4-hydroxymethylpyridine (I) with tert-butyldimethylsilyl chloride and imidazole. Deprotonation of (II) by means of LDA in cold THF, followed by condensation with 4-fluorobenzaldehyde (III), furnished the protected diol adduct (IV), which was further desilylated upon treatment with tetrabutylammonium fluoride in THF. Oxidation of the resultant diol (V) under Swern conditions provided diketone (VI). The triaryl imidazole (VIII) was then obtained by condensation of diketone (VI) with 4-(methylsulfanyl)benzaldehyde (VII) in the presence of ammonium acetate in refluxing HOAc. Finally, oxidation of the thioether function of (VIII) with K-2S2O8 furnished the title sulfoxide.

参考文献中间体

合成目标

【1】 Adams, J.L.; Gallagher, T.F.; Lee, J.C.; White, J.R. (GlaxoSmithKline plc); Imidazole derivs. and their use as cytokine inhibitors. EP 0623126; EP 0943616; JP 1995503017; US 5686455; WO 9314081 .

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)	32835	4-pyridinylmethanol	586-95-8	C₆H₇NO	详情	详情
(II)	22829	4-([[tert-butyl(dimethyl)silyl]oxy]methyl)pyridine; tert-butyl(dimethyl)silyl 4-pyridinylmethyl ether		C₁₂H₂₁NOSi	详情	详情
(III)	12337	4-fluorobenzaldehyde	459-57-4	C₇H₅FO	详情	详情
(IV)	55081	2-{[tert-butyl(dimethyl)silyl]oxy}-1-(4-fluorophenyl)-2-(4-pyridinyl)-1-ethanol		C₁₉H₂₆FNO₂Si	详情	详情
(V)	55082	1-(4-fluorophenyl)-2-(4-pyridinyl)-1,2-ethanediol		C₁₃H₁₂FNO₂	详情	详情
(VI)	37913	1-(4-fluorophenyl)-2-(4-pyridinyl)-1,2-ethanedione		C₁₃H₈FNO₂	详情	详情
(VII)	18815	4-(methylsulfanyl)benzaldehyde; 4-(methylmercapto)benzaldehyde	3446-89-7	C₈H₈OS	详情	详情
(VIII)	55083	4-{5-(4-fluorophenyl)-2-[4-(methylsulfanyl)phenyl]-1H-imidazol-4-yl}pyridine; 4-[5-(4-fluorophenyl)-4-(4-pyridinyl)-1H-imidazol-2-yl]phenyl methyl sulfide		C₂₁H₁₆FN₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Selenium dioxide oxidation of diaryl ethanone (I) afforded diketone (II), which was cyclized to the imidazole (III) by reaction with hexamethylenetetramine and ammonium acetate in hot AcOH. Alkylation of (III) with 1-bromo-3-phenylpropane (IV) in the presence of NaH gave rise to a mixture of regioisomeric imidazoles (V) and (VI) that were separated by column chromatography. After deprotonation of the desired isomer (V) with LDA, treatment with iodine produced iodoimidazole (VII). Then, palladium-catalyzed coupling of (VII) with 3-butyn-1-ol (VIII) yielded the title compound.

参考文献中间体

合成目标

【1】 Malloy, E.; Wachter, M.P.; Wu, W.; Beers, S.A. (Ortho-McNeil Pharmaceutical, Inc.); Substd. imidazoles useful in the treatment of inflammatory diseases. EP 1028954; US 5965583; WO 9847892 .

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)	37912	2-(4-fluorophenyl)-1-(4-pyridinyl)-1-ethanone		C₁₃H₁₀FNO	详情	详情
(II)	37913	1-(4-fluorophenyl)-2-(4-pyridinyl)-1,2-ethanedione		C₁₃H₈FNO₂	详情	详情
(III)	33798	4-[4-(4-fluorophenyl)-1H-imidazol-5-yl]pyridine		C₁₄H₁₀FN₃	详情	详情
(IV)	20884	1-(3-bromopropyl)benzene	637-59-2	C₉H₁₁Br	详情	详情
(V)	37914	4-[4-(4-fluorophenyl)-1-(3-phenylpropyl)-1H-imidazol-5-yl]pyridine		C₂₃H₂₀FN₃	详情	详情
(VI)	37915	4-[5-(4-fluorophenyl)-1-(3-phenylpropyl)-1H-imidazol-4-yl]pyridine		C₂₃H₂₀FN₃	详情	详情
(VII)	37916	4-[4-(4-fluorophenyl)-2-iodo-1-(3-phenylpropyl)-1H-imidazol-5-yl]pyridine		C₂₃H₁₉FIN₃	详情	详情
(VIII)	32507	3-butyn-1-ol	927-74-2	C₄H₆O	详情	详情

Extended Information