benzyl 5-ethyl-4'-fluoro-4-(3-iodopropoxy)[1,1'-biphenyl]-2-yl ether; 2-(benzyloxy)-5-ethyl-4'-fluoro-4-(3-iodopropoxy)-1,1'-biphenyl -Drug Synthesis Database

【结构式】

【分子编号】16213

【品名】benzyl 5-ethyl-4'-fluoro-4-(3-iodopropoxy)[1,1'-biphenyl]-2-yl ether; 2-(benzyloxy)-5-ethyl-4'-fluoro-4-(3-iodopropoxy)-1,1'-biphenyl

【CA登记号】

【分子式】C₂₄H₂₄FIO₂

【分子量】490.3562332

【元素组成】C 58.79% H 4.93% F 3.87% I 25.88% O 6.53%

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：(VI)

The biphenyl side chain of LY293111 can be constructed as illustrated in Scheme 19757001a: 4-Benzyloxy-2-hydroxyacetophenone (I) is alkylated with 1-bromo-3-chloropropane to provide compound (II). Reduction of the keto group with triethylsilane in trifluoroacetic acid provides (III), which is then regiospecifically brominated with N-bromosuccinimide to give (IV). A Suzuki biaryl coupling of (IV) with 4-fluorophenylboronic acid is used to prepare chloride (V), which is treated with sodium iodide in refluxing 2-butanone to give intermediate iodide (VI).

参考文献中间体

合成目标

【1】 Schmittling, E.A.; Sawyer, J.S.; Synthesis of diaryl ethers, diaryl thioethers, and diaryl amines mediated by potassium fluoride-alumina and 18-crown-6. J Org Chem 1993, 58, 3229-30.
【2】 Sawyer, J.S.; Bach, N.J.; Baker, S.R.; et al.; Synthetic and structure/activity studies on acid-substituted 2-arylphenols: The discovery of 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]propoxy]phenoxy]benzoic acid, a high-affinity leukotriene B4 receptor antagonist. J Med Chem 1995, 38, 22, 4411-32.
【3】 Sawyer, J.S.; Baldwin, R.F.; Sofia, M.J.; et al.; Biphenylyl-substituted xanthones: Highly potent leukotriene B4 receptor antagonists. J Med Chem 1993, 36, 24, 3982-4.
【4】 Sawyer, J.S.; LY-293111 Sodium. Drugs Fut 1996, 21, 6, 610.
【5】 Sawyer, J.S.; Baldwin, R.F.; Saussy, D.L. Jr.; Froelich, L.L.; Jackson, W.T.; Diaryl ether/carboxylic acid derivatives of LY255283: Receptor antagonists of leukotriene B4. Bioorg Med Chem Lett 1993, 3, 10, 1985-90.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	10358	1-Bromo-3-chloropropane	109-70-6	C₃H₆BrCl	详情	详情
	38403	4-fluorophenylboronic acid	1765-93-1	C₆H₆BFO₂	详情	详情
(I)	16208	4'-Benzyloxy-2'-hydroxyacetophenone; 1-[4-(Benzyloxy)-2-hydroxyphenyl]-1-ethanone	29682-12-0	C₁₅H₁₄O₃	详情	详情
(II)	16209	1-[4-(benzyloxy)-2-(3-chloropropoxy)phenyl]-1-ethanone		C₁₈H₁₉ClO₃	详情	详情
(III)	16210	4-(benzyloxy)-2-(3-chloropropoxy)-1-ethylbenzene; benzyl 3-(3-chloropropoxy)-4-ethylphenyl ether		C₁₈H₂₁ClO₂	详情	详情
(IV)	16211	benzyl 2-bromo-5-(3-chloropropoxy)-4-ethylphenyl ether; 1-(benzyloxy)-2-bromo-5-(3-chloropropoxy)-4-ethylbenzene		C₁₈H₂₀BrClO₂	详情	详情
(V)	16212	benzyl 4-(3-chloropropoxy)-5-ethyl-4'-fluoro[1,1'-biphenyl]-2-yl ether; 2-(benzyloxy)-4-(3-chloropropoxy)-5-ethyl-4'-fluoro-1,1'-biphenyl		C₂₄H₂₄ClFO₂	详情	详情
(VI)	16213	benzyl 5-ethyl-4'-fluoro-4-(3-iodopropoxy)[1,1'-biphenyl]-2-yl ether; 2-(benzyloxy)-5-ethyl-4'-fluoro-4-(3-iodopropoxy)-1,1'-biphenyl		C₂₄H₂₄FIO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The final coupling of fragments (VI) and (X) to give (XIII) is shown in Scheme 19757001c, and is accomplished in the presence of potassium carbonate in N,N-dimethylformamide. The final deprotection sequence is effected by hydrogenolysis of the benzyl ether followed by hydrolysis of the resulting ester to provide LY293111 as the sodium salt.

参考文献中间体

合成目标

【1】 Schmittling, E.A.; Sawyer, J.S.; Synthesis of diaryl ethers, diaryl thioethers, and diaryl amines mediated by potassium fluoride-alumina and 18-crown-6. J Org Chem 1993, 58, 3229-30.
【2】 Sawyer, J.S.; LY-293111 Sodium. Drugs Fut 1996, 21, 6, 610.
【3】 Sawyer, J.S.; Bach, N.J.; Baker, S.R.; et al.; Synthetic and structure/activity studies on acid-substituted 2-arylphenols: The discovery of 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5-hydroxyphenoxy]propoxy]phenoxy]benzoic acid, a high-affinity leukotriene B4 receptor antagonist. J Med Chem 1995, 38, 22, 4411-32.
【4】 Sawyer, J.S.; Baldwin, R.F.; Sofia, M.J.; et al.; Biphenylyl-substituted xanthones: Highly potent leukotriene B4 receptor antagonists. J Med Chem 1993, 36, 24, 3982-4.
【5】 Sawyer, J.S.; Baldwin, R.F.; Saussy, D.L. Jr.; Froelich, L.L.; Jackson, W.T.; Diaryl ether/carboxylic acid derivatives of LY255283: Receptor antagonists of leukotriene B4. Bioorg Med Chem Lett 1993, 3, 10, 1985-90.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VI)	16213	benzyl 5-ethyl-4'-fluoro-4-(3-iodopropoxy)[1,1'-biphenyl]-2-yl ether; 2-(benzyloxy)-5-ethyl-4'-fluoro-4-(3-iodopropoxy)-1,1'-biphenyl	C₂₄H₂₄FIO₂	详情	详情
(X)	16217	methyl 2-(3-hydroxy-2-propylphenoxy)benzoate	C₁₇H₁₈O₄	详情	详情
(XIII)	16220	methyl 2-[3-(3-[[6-(benzyloxy)-3-ethyl-4'-fluoro[1,1'-biphenyl]-4-yl]oxy]propoxy)-2-propylphenoxy]benzoate	C₄₁H₄₁FO₆	详情	详情

Extended Information