(13S,17R)-17-acetyl-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one -Drug Synthesis Database

【结构式】

【分子编号】40867

【品名】(13S,17R)-17-acetyl-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one

【CA登记号】14340-01-3

【分子式】C₂₀H₂₆O₃

【分子量】314.42464

【元素组成】C 76.4% H 8.33% O 15.27%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(III)

The reaction of cyanohydrineketal (I) with dimethyl(chloromethyl)silyl chloride (A), TEA and DMAP in THF gives the silylated cyanohydrine (II), which is treated with Li and 4,4'-di-tert-butylbiphenyl (DBB) in THF followed by acidification with HCl yields 17alpha-hydroxy-19-norpregna-4,9-diene-3,20-dione (III). The reaction of (III) with ethylene-glycol and TsOH afford the bis ethylenedioxy derivative (IV), which is epoxidized with H2O2 and trifluoroacetone in dichloromethane affording the monoepoxide (V). The Grignard condensation of (V) with 4-(dimethylamino)phenylmagnesium bromide in THF provides the 11-beta-(dimethylamino) derivative (VII), which is dehydrated and deprotected with sulfuric acid in refluxing ethanol to furnish 11-beta-[4-(dimethylamino)phenyl]-17alpha-hydroxy-19-norpregna-4,9-diene-3,20-dione (VIII). Finally, this compound is acetylated with AcOH and trifluoroacetic anhydride in dichloromethane.

参考文献中间体

合成目标

【1】 Wronski, R.; et al.; A brain derived peptide preparation reduces the translation dependent loss of a cytoskeletal protein in primary cultured chicken neurons. J Neural Transm 2000, 59, 263.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	40865	chloro(chloromethyl)dimethylsilane	1719-57-9	C₃H₈Cl₂Si	详情	详情
(I)	40864			C₂₁H₂₇NO₃	详情	详情
(II)	40866			C₂₄H₃₄ClNO₃Si	详情	详情
(III)	40867	(13S,17R)-17-acetyl-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	14340-01-3	C₂₀H₂₆O₃	详情	详情
(IV)	40868			C₂₄H₃₄O₅	详情	详情
(V)	40869			C₂₄H₃₄O₆	详情	详情
(VI)	10863	Bromo[4-(dimethylamino)phenyl]magnesium	7353-91-5	C₈H₁₀BrMgN	详情	详情
(VII)	40870			C₃₂H₄₅NO₆	详情	详情
(VIII)	40871	(13S,17R)-17-acetyl-11-[4-(dimethylamino)phenyl]-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₈H₃₅NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Rao PN. 2000. A practical large-scale synthesis of 17 alpha-acetoxy-ll beta-(4-N,N-dimethylaminophenyl)-19-norpregna-4,9-diene-3,20-dione (CDB-2914). Steroids, 65 (7): 395～400

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)	40864			C₂₁H₂₇NO₃	详情	详情
(II)	40866			C₂₄H₃₄ClNO₃Si	详情	详情
(III)	40867	(13S,17R)-17-acetyl-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	14340-01-3	C₂₀H₂₆O₃	详情	详情
(IV)	40868			C₂₄H₃₄O₅	详情	详情
(V)	40869			C₂₄H₃₄O₆	详情	详情
(VI)	10863	Bromo[4-(dimethylamino)phenyl]magnesium	7353-91-5	C₈H₁₀BrMgN	详情	详情
(VII)	40870			C₃₂H₄₅NO₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Kim H, Pemmaraju N, Simmons Anne-Marie.2004.Process for the preparation of 17α-acetoxy-11β-[4-(N,N-dimethylamino) phenyl]-19-norpregna-4,9-diene-3,20-dione and new intermediates of the process. WO 2004078709 A2.

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)	40867	(13S,17R)-17-acetyl-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	14340-01-3	C₂₀H₂₆O₃	详情	详情
(II)	67474	(13R,17S)-17-acetyl-13-methyl-3-oxo-2,3,6,7,8,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl acetate		C₂₂H₂₈O₄	详情	详情
(III)	67466	1-((8R,13R,14R)-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydrospiro[cyclopenta[a]phenanthrene-3,2'-[1,3]dioxolan]-17-yl)ethanone		C₂₂H₃₀O₄	详情	详情
(IV)	67475	1-((5S,10S,13R,17S)-17-hydroxy-13- methyl-1,2,4,6,7,8,12,13,14,15,16,17- dodecahydrospiro[5,10-epoxycyclopenta[a] phenanthrene-3,2'-[1,3]dioxolan]-17-yl)ethanone		C₂₂H₃₀O₅	详情	详情
(V)	67476	1-((5S,13R,17S)-11-(4-(dimethylamino) phenyl)-5,17-dihydroxy-13-methyl- 1,2,4,5,6,7,8,11,12,13,14,15,16,17- tetradecahydrospiro[cyclopenta[a]phenanthrene-3,2'- [1,3]dioxolan]-17-yl)ethanone		C₃₀H₄₁NO₅	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Kim Hyun K, San Antonio, Caemie Kirk, et al.1996.Method for preparing 17α-acetoxy-11β-(4-N,N-dimethylamino Phenyl)-19-norpregna-4,9-diene-3,20-dione, Intermediates useful in the method, and method for the preparation of such intermediates. US 9603660.

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)	40864			C₂₁H₂₇NO₃	详情	详情
(II)	40866			C₂₄H₃₄ClNO₃Si	详情	详情
(III)	40867	(13S,17R)-17-acetyl-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one	14340-01-3	C₂₀H₂₆O₃	详情	详情
(IV)	40868			C₂₄H₃₄O₅	详情	详情
(V)	40869			C₂₄H₃₄O₆	详情	详情
(VI)	40870			C₃₂H₄₅NO₆	详情	详情
(VII)	40871	(13S,17R)-17-acetyl-11-[4-(dimethylamino)phenyl]-17-hydroxy-13-methyl-1,2,4,6,7,8,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthren-3-one		C₂₈H₃₅NO₃	详情	详情

Extended Information