(4S,5aR)-5-ethyl-10-methoxy-4-propyl-4,5,5a,6-tetrahydrodibenzo[cd,f]indol-9-yl methyl ether -Drug Synthesis Database

【结构式】

【分子编号】28986

【品名】(4S,5aR)-5-ethyl-10-methoxy-4-propyl-4,5,5a,6-tetrahydrodibenzo[cd,f]indol-9-yl methyl ether

【CA登记号】

【分子式】C₂₂H₂₇NO₂

【分子量】337.46192

【元素组成】C 78.3% H 8.06% N 4.15% O 9.48%

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：(V)

The acylation of 9-ethylamino-8-bromo-3,4-dimethoxyphenanthrene (I) with butyryl chloride (II) in CH2Cl2 gives 9-(N-ethyl-N-butyrylamino)-8-bromo-3,4-dimethoxyphenanthrene (III), which is cyclized by means of butyllithium in THF yielding 5-ethyl-4,5-dihydro-9,10-dimethoxy-4-n-propyldibenz[cd,f]indole-4-ol (IV). The reduction of (IV) with Zn-HgCl2 in refluxing ethanol water affords 5-ethyl-4,5,5a,6-tetrahydro-9,10-diethoxy-4-n-propyldibenz[cd,f]indole (V), which is finally demethylated by means of refluxing aqueous 47% HBr.

参考文献中间体

合成目标

【1】 Giger, R.K.A. (Novartis AG); Nouveaux derives du dibenz[cd,f]indole, leur preparation et leur application comme medicaments. DE 3124086; FR 2485530; FR 2510996; WO 8200143 .
【2】 Castaner, J.; Serradell, M.N.; 201678. Drugs Fut 1985, 10, 2, 99.

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)	28983	8-bromo-N-ethyl-3,4-dimethoxy-9-phenanthrenamine		C₁₈H₁₈BrNO₂	详情	详情
(II)	10792	Butanoyl chloride; Butyryl chloride	141-75-3	C₄H₇ClO	详情	详情
(III)	28984	N-(8-bromo-3,4-dimethoxy-9-phenanthryl)-N-ethylbutanamide		C₂₂H₂₄BrNO₃	详情	详情
(IV)	28985	(4R)-5-ethyl-9,10-dimethoxy-4-propyl-4,5-dihydrodibenzo[cd,f]indol-4-ol		C₂₂H₂₅NO₃	详情	详情
(V)	28986	(4S,5aR)-5-ethyl-10-methoxy-4-propyl-4,5,5a,6-tetrahydrodibenzo[cd,f]indol-9-yl methyl ether		C₂₂H₂₇NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The reaction of 3,4-dimethoxyphenanthrene-9-carboxylic acid (VI) first with trifluoroacetic anhydride and then with sodium azide gives 9-amino-3,4-dimethoxyphenanthrene (VII), which is acetylated with acetyl chloride in CH2Cl2 yielding 9-acetylamino-3,4-dimethoxyphenanthrene (VIII). The reduction of (VIII) with diborane in THF affords 9-ethylamino-3,4-dimethoxyphenanthrene (IX), which is cyclized with CO2 by means of n-butyllithium in THF affording 5-ethyl-4,5-dihydro-9,10-dimethoxy-4-oxodibenz[cd,f]indole (X). Finally, this compound is submitted to a Grignard synthesis with propylmagnesium bromide (A) in THF to give (IV), already obtained.

参考文献中间体

合成目标

【1】 Giger, R.K.A. (Novartis AG); Nouveaux derives du dibenz[cd,f]indole, leur preparation et leur application comme medicaments. DE 3124086; FR 2485530; FR 2510996; WO 8200143 .
【2】 Castaner, J.; Serradell, M.N.; 201678. Drugs Fut 1985, 10, 2, 99.

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)	10790	Bromo(propyl)magnesium；bromopropylMagnesium；4-propylbutyrolactone；propylmagnesiumbromide；n-propylmagnesium bromide；Bromopropylmagnesium;	927-77-5	C₃H₇BrMg	详情	详情
(IV)	28985	(4R)-5-ethyl-9,10-dimethoxy-4-propyl-4,5-dihydrodibenzo[cd,f]indol-4-ol		C₂₂H₂₅NO₃	详情	详情
(V)	28986	(4S,5aR)-5-ethyl-10-methoxy-4-propyl-4,5,5a,6-tetrahydrodibenzo[cd,f]indol-9-yl methyl ether		C₂₂H₂₇NO₂	详情	详情
(VI)	28987	3,4-dimethoxy-9-phenanthrenecarboxylic acid		C₁₇H₁₄O₄	详情	详情
(VII)	28988	3,4-dimethoxy-9-phenanthrenamine		C₁₆H₁₅NO₂	详情	详情
(VIII)	28989	N-(3,4-dimethoxy-9-phenanthryl)acetamide		C₁₈H₁₇NO₃	详情	详情
(IX)	28990	N-(3,4-dimethoxy-9-phenanthryl)-N-ethylamine		C₁₈H₁₉NO₂	详情	详情
(X)	28991	5-ethyl-9,10-dimethoxydibenzo[cd,f]indol-4(5H)-one		C₁₉H₁₇NO₃	详情	详情

Extended Information