4-(4-methoxy-1-benzothiophen-2-yl)phenyl methyl ether -Drug Synthesis Database

【结构式】

【分子编号】25758

【品名】4-(4-methoxy-1-benzothiophen-2-yl)phenyl methyl ether

【CA登记号】

【分子式】C₁₆H₁₄O₂S

【分子量】270.35196

【元素组成】C 71.08% H 5.22% O 11.84% S 11.86%

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：(V)

Alkylation of 3-methoxybenzenethiol (I) with 4'-methoxyphenacyl bromide (II) afforded sulfide (III). Cyclization of (III) with concomitant rearrangement in the presence of polyphosphoric acid produced a mixture of regioisomers (IV) and (V) that were separated by their different solubility in acetone. Then, Friedel-Crafts acylation of the desired insoluble isomer (IV) with 3,4,5-trimethoxybenzoyl chloride (VI) in the presence of AlCl3 provided the title ketone, which was separated from some demethylated byproduct by means of silica gel chromatography.

参考文献中间体

合成目标

【1】 Lee, B.; et al.; Hepatocyte gene therapy in a large animal: A neonatal bovine model of citrullinemia. Proc Natl Acad Sci USA 1999, 96, 7, 3981.
【2】 Jones, C.D.; et al.; Antiestrogens. 2. Structure-activity studies in a series of 3-aroyl-2-arylbenzo[b]thiophene derivatives leading to [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]-phenyl]methanone hydrochloride (LY156758), a remarkably effec. J Med Chem 1984, 27, 8, 1057.
【3】 Carlson, D.G.; Cullinan, G.J.; Fahey, K.J.; Jackson, W.T.; Roehm, N.W.; Spaethe, S.M. (Eli Lilly and Company); Novel benzothiophene cpds. and methods. EP 0732331; JP 1999501932; WO 9628156 .
【4】 Pinney, K.G. (Baylor University); Anti-mitotic agents which inhibit tubulin polymerization. US 5886025 .

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)	25756	3-methoxybenzenethiol	15570-12-4	C₇H₈OS	详情	详情
(II)	21991	2-Methoxyphenacyl bromide; 2-bromo-1-(4-methoxyphenyl)-1-ethanone	2632-13-5	C₉H₉BrO₂	详情	详情
(III)	25757	1-(4-methoxyphenyl)-2-[(3-methoxyphenyl)sulfanyl]-1-ethanone		C₁₆H₁₆O₃S	详情	详情
(IV)	10121	4-(6-Methoxy-1-benzothiophen-2-yl)phenyl methyl ether; 6-Methoxy-2-(4-methoxyphenyl)-1-benzothiophene	63675-74-1	C₁₆H₁₄O₂S	详情	详情
(V)	25758	4-(4-methoxy-1-benzothiophen-2-yl)phenyl methyl ether		C₁₆H₁₄O₂S	详情	详情
(VI)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情

Extended Information