2-(4-fluorophenyl)-1-(4-pyridinyl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】37912

【品名】2-(4-fluorophenyl)-1-(4-pyridinyl)-1-ethanone

【CA登记号】

【分子式】C₁₃H₁₀FNO

【分子量】215.2269432

【元素组成】C 72.55% H 4.68% F 8.83% N 6.51% O 7.43%

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：(I)

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

合成路线2

该中间体在本合成路线中的序号：(I)

Condensation of 2-(4-fluorophenyl)-1-(4-pyridyl)ethanone (I) with dimethylformamide-dimethylacetal gives the enamino ketone (II). This is cyclized with thiourea (III) in the presence of NaOEt to produce the pyrimidine-2-thione (IV). Finally, S-alkylation of (IV) with 2-(methylsulfinyl)benzyl chloride (V) yields the target compound.

参考文献中间体

合成目标

【1】 Wagner, G.K.; Laufer, S.A.; From imidazoles to pyrimidines: New inhibitors of cytokine release. J Med Chem 2002, 45, 13, 2733.

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)	59069	(Z)-3-(dimethylamino)-2-(4-fluorophenyl)-1-(4-pyridinyl)-2-propen-1-one		C₁₆H₁₅FN₂O	详情	详情
(III)	10180	Thiourea	62-56-6	CH₄N₂S	详情	详情
(IV)	59070	5-(4-fluorophenyl)-4-(4-pyridinyl)-2(1H)-pyrimidinethione		C₁₅H₁₀FN₃S	详情	详情
(V)	59071	2-(chloromethyl)phenyl methyl sulfoxide; [2-(chloromethyl)phenyl](methyl)oxo-lambda~4~-sulfane		C₈H₉ClOS	详情	详情

Extended Information