SP-500263, -Drug Synthesis Database

【结构式】

【药物名称】SP-500263

【化学名称】7-Hydroxy-3-phenyl-4-[4-[2-(1-piperidinyl)ethoxy]benzyl]-2H-1-benzopyran-2-one hydrochloride

【CA登记号】280137-80-6 (free base)

【分子式】C₂₉H₃₀ClNO₄

【分子量】492.01975

【开发单位】Signal (Originator)

【药理作用】Bone Diseases, Treatment of, METABOLIC DRUGS, ONCOLYTIC DRUGS, Selective Estrogen Receptor Modulators (SERM)

合成路线1

Friedel-Crafts acylation of 3-methoxyphenol (I) with 4-hydroxyphenylacetic acid (II) in the presence of ZnCl2 and POCl3 furnished ketone (III), which was subsequently protected with triisopropylsilyl chloride and Et3N to yield the mono-silyl ether (IV). Coumarin (VI) was then synthesized by condensation of hydroxy ketone (IV) with phenylacetyl chloride (V) in the presence of K2CO3. Alkylation of the phenolic hydroxyl group of (VI) with N-(2-chloroethyl)piperidine (VII) gave the piperidinylethyl ether (VIII). Finally, selective methyl ether hydrolysis using HBr in refluxing HOAc led to the title compound.

参考文献中间体

【1】 Bhagwat, S.S.; McKie, J.A.; Khammungkhune, S. (Signal Pharmaceuticals, Inc.); Cpds. and methods for modulation of estrogen receptors. WO 0149673 .

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)	22389	3-Methoxyphenol	150-19-6	C₇H₈O₂	详情	详情
(II)	18430	2-(4-Hydroxyphenyl)acetic acid; 4-Hydroxyphenylacetic acid	156-38-7	C₈H₈O₃	详情	详情
(III)	56078	1-(2-hydroxy-4-methoxyphenyl)-2-(4-hydroxyphenyl)-1-ethanone		C₁₅H₁₄O₄	详情	详情
(IV)	56079	1-(2-hydroxy-4-methoxyphenyl)-2-{4-[(triisopropyl-lambda~4~-sulfanyl)oxy]phenyl}-1-ethanone		C₂₄H₃₄O₄S	详情	详情
(V)	25890	2-phenylacetyl chloride；Phenylacetyl chloride;Phenacetyl chloride;Benzeneacetyl chloride	103-80-0	C₈H₇ClO	详情	详情
(VI)	56080	4-(4-hydroxybenzyl)-7-methoxy-3-phenyl-2H-chromen-2-one		C₂₃H₁₈O₄	详情	详情
(VII)	10117	1-(2-Chloroethyl)piperidine; N-(2-Chloroethyl)piperidine	1932-03-2	C₇H₁₄ClN	详情	详情
(VIII)	56081	7-methoxy-3-phenyl-4-{4-[2-(1-piperidinyl)ethoxy]benzyl}-2H-chromen-2-one		C₃₀H₃₁NO₄	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)