-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】2,8-Dihydroxy-5-[4-[2-(1-piperidinyl)ethoxy]phenyl]-5,6-dihydrobenzo[c]phenanthridine

【CA登记号】

【分子式】C₃₀H₃₀N₂O₃

【分子量】466.5852

【开发单位】Lilly (Originator)

【药理作用】Bone Diseases, Treatment of, CARDIOVASCULAR DRUGS, Lipoprotein Disorders, Treatment of , METABOLIC DRUGS, ONCOLYTIC DRUGS, Restenosis Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, Treatment of Osteoporosis, Antiestrogens, Estrogen Agonists

合成路线1 合成路线2

合成路线1

Imine (III) was prepared by condensation of 6-methoxy-1-tetralone (I) with p-aminophenol (II) at 180 C. After silylation of the hydroxyl group of (III) with tert-butyldimethylsilyl chloride to give (IV), acylation of the enamine function with 2-bromo-5-methoxybenzoyl chloride (V) yielded enamide (VI). Halogenation of (VI) with N-bromosuccinimide gave the beta-bromo enamide (VII). Photocyclization of (VII) produced the benzophenanthridine (VIII), which was further dehydrogenated with DDQ providing (IX). Desilylation of (IX) to afford phenol (X) was achieved by treatment with hydrogen fluoride-pyridine.

参考文献中间体

【1】 Grese, T.A.; et al.; Photochemical synthesis of N-arylbenzophenanthridine selective estrogen receptor modulators (SERMs). J Med Chem 2001, 44, 17, 2857.

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)	17594	6-methoxy-3,4-dihydro-1(2H)-naphthalenone; 6-Methoxytetralone; 6-Methoxy-1-tetralone; 3,4-dihydro-6-methoxy-1(2H)-naphthalenone	1078-19-9	C₁₁H₁₂O₂	详情	详情
(II)	15715	4-Aminophenol	123-30-8	C₆H₇NO	详情	详情
(III)	50224	4-[[6-methoxy-3,4-dihydro-1(2H)-naphthalenylidene]amino]phenol		C₁₇H₁₇NO₂	详情	详情
(IV)	50225	N-(4-[[tert-butyl(dimethyl)silyl]oxy]phenyl)-N-[6-methoxy-3,4-dihydro-1(2H)-naphthalenylidene]amine; 4-[[tert-butyl(dimethyl)silyl]oxy]-N-[6-methoxy-3,4-dihydro-1(2H)-naphthalenylidene]aniline		C₂₃H₃₁NO₂Si	详情	详情
(V)	50226	2-Bromo-5-methoxybenzoyl chloride	56658-04-9	C₈H₆BrClO₂	详情	详情
(VI)	50227	2-bromo-N-(4-[[tert-butyl(dimethyl)silyl]oxy]phenyl)-5-methoxy-N-(6-methoxy-3,4-dihydro-1-naphthalenyl)benzamide		C₃₁H₃₆BrNO₄Si	详情	详情
(VII)	50228	2-bromo-N-(2-bromo-6-methoxy-3,4-dihydro-1-naphthalenyl)-N-(4-[[tert-butyl(dimethyl)silyl]oxy]phenyl)-5-methoxybenzamide		C₃₁H₃₅Br₂NO₄Si	详情	详情
(VIII)	50229	5-(4-[[tert-butyl(dimethyl)silyl]oxy]phenyl)-2,8-dimethoxy-11,12-dihydrobenzo[c]phenanthridin-6(5H)-one		C₃₁H₃₅NO₄Si	详情	详情
(IX)	50230	5-(4-[[tert-butyl(dimethyl)silyl]oxy]phenyl)-2,8-dimethoxybenzo[c]phenanthridin-6(5H)-one		C₃₁H₃₃NO₄Si	详情	详情
(X)	50231	5-(4-hydroxyphenyl)-2,8-dimethoxybenzo[c]phenanthridin-6(5H)-one		C₂₅H₁₉NO₄	详情	详情

合成路线2

Condensation of phenol (X) with N-(2-hydroxyethyl)piperidine (XI) under Mitsunobu conditions furnished ether (XII). The lactam function of (XII) was then reduced with LiAlH4 to produce (XIII). Finally, methyl ether cleavage in (XIII) was carried out by treatment with AlCl3 in the presence of EtSH.

参考文献中间体

【1】 Grese, T.A.; et al.; Photochemical synthesis of N-arylbenzophenanthridine selective estrogen receptor modulators (SERMs). J Med Chem 2001, 44, 17, 2857.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(X)	50231	5-(4-hydroxyphenyl)-2,8-dimethoxybenzo[c]phenanthridin-6(5H)-one		C₂₅H₁₉NO₄	详情	详情
(XI)	37675	2-(1-piperidinyl)-1-ethanol	3040-44-6	C₇H₁₅NO	详情	详情
(XII)	50233	4-[2,8-dimethoxybenzo[c]phenanthridin-5(6H)-yl]phenyl 2-(1-piperidinyl)ethyl ether; 2,8-dimethoxy-5-[4-[2-(1-piperidinyl)ethoxy]phenyl]-5,6-dihydrobenzo[c]phenanthridine		C₃₂H₃₄N₂O₃	详情	详情
(XIII)	50232	2,8-dimethoxy-5-[4-[2-(1-piperidinyl)ethoxy]phenyl]benzo[c]phenanthridin-6(5H)-one		C₃₂H₃₂N₂O₄	详情	详情

Extended Information