4-[2-(tert-butyl)-4-(4-fluorophenyl)-1-hydroxy-1H-imidazol-5-yl]-2(1H)-pyridinone -Drug Synthesis Database

【结构式】

【分子编号】63666

【品名】4-[2-(tert-butyl)-4-(4-fluorophenyl)-1-hydroxy-1H-imidazol-5-yl]-2(1H)-pyridinone

【CA登记号】

【分子式】C₁₈H₁₈FN₃O₂

【分子量】327.3583432

【元素组成】C 66.04% H 5.54% F 5.8% N 12.84% O 9.77%

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：(VI)

Condensation of 2-fluoro-4-methylpyridine (I) with ethyl 4-fluorobenzoate (II) by means of sodium bis(trimethylsilyl)amide provides the diaryl ethanone (III). Subsequent nitrosation of ketone (III) with tert-butyl nitrite under acidic conditions furnishes oxime (IV). Cyclization of keto oxime (IV) with trimethylacetaldehyde (V) in the presence of ammonium acetate in boiling AcOH proceeds with concomitant hydrolysis of the fluoro group to produce the N-hydroxy imidazole (VI). Reduction of (VI) employing TiCl3 gives imidazole (VII). Finally, the photochemical cyclization of diarylimidazole (VII) leads to the target tetracyclic compound (1, 2).

参考文献中间体

合成目标

【1】 Thompson, J.E.; Cubbon, R.M.; Cummings, R.T.; Wicker, L.S.; Franksun, R.; Cunningham, B.R.; Cameron, P.M.; Meinke, P.T.; Liverton, N.; Weng, Y.; DeMartino, J.A.; Photochemical preparation of a pyridone containing tetracycle: A jak protein kinase inhibitor. Bioorg Med Chem Lett 2002, 12, 8, 1219.
【2】 Sinclair, P.J.; Goulet, J.L.; Hong, X.; Thompson, J.E.; Cubbon, R.M.; Cummings, R.T. (Merck & Co., Inc.); Benzimidazo[4,5-f]isoquinolinone derivs.. WO 0311285 .

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)	18296	2-Fluoro-4-methylpyridine	461-87-0	C₆H₆FN	详情	详情
(II)	22830	ethyl 4-fluorobenzoate	451-46-7	C₉H₉FO₂	详情	详情
(III)	63664	1-(4-fluorophenyl)-2-(2-fluoro-4-pyridinyl)-1-ethanone		C₁₃H₉F₂NO	详情	详情
(IV)	63665	1-(4-fluorophenyl)-2-(2-fluoro-4-pyridinyl)-1,2-ethanedione 2-oxime		C₁₃H₈F₂N₂O₂	详情	详情
(V)	19797	Trimethylacetaldehyde; pivalaldehyde; 2,2-Dimethylpropionaldehyde; 2,2-Dimethylpropanal	630-19-3	C₅H₁₀O	详情	详情
(VI)	63666	4-[2-(tert-butyl)-4-(4-fluorophenyl)-1-hydroxy-1H-imidazol-5-yl]-2(1H)-pyridinone		C₁₈H₁₈FN₃O₂	详情	详情
(VII)	63667	4-[2-(tert-butyl)-4-(4-fluorophenyl)-1H-imidazol-5-yl]-2(1H)-pyridinone		C₁₈H₁₈FN₃O	详情	详情

Extended Information