N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide -Drug Synthesis Database

【结构式】

【分子编号】18479

【品名】N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide

【CA登记号】64-86-8

【分子式】C₂₂H₂₅NO₆

【分子量】399.44364

【元素组成】C 66.15% H 6.31% N 3.51% O 24.03%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(I)

Thiocolchicine (II) was prepared from colchicine (I) by treatment with sodium methylthiolate. Then, hydrolysis of acetamide group with methanolic HCl afforded deacetyl thiocolchicine (III). Subsequent acylation with p-nitrobenzoyl chloride (IV) in the presence of pyridine provided amide (V), which was demethylated with excess BBr3 to give the corresponding triphenol (VI). Finally, esterification with acetyl chloride in the presence of pyridine and 4-(dimethylamino)pyridine furnished the target triacetate.

参考文献中间体

合成目标

【1】 Guan, J.; et al.; Antitumor agents. 185. Synthesis and biological evaluation of tridemethylthiocolchicine analogues as novel topoisomerase II inhibitors. J Med Chem 1998, 41, 11, 1956.

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)	18479	N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide	64-86-8	C₂₂H₂₅NO₆	详情	详情
(II)	18480	N-[(7S)-1,2,3-trimethoxy-10-(methylsulfanyl)-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide		C₂₂H₂₅NO₅S	详情	详情
(III)	18481	(7S)-7-amino-1,2,3-trimethoxy-10-(methylsulfanyl)-6,7-dihydrobenzo[a]heptalen-9(5H)-one		C₂₀H₂₃NO₄S	详情	详情
(IV)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(V)	18483	4-nitro-N-[(7S)-1,2,3-trimethoxy-10-(methylsulfanyl)-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]benzamide		C₂₇H₂₆N₂O₇S	详情	详情
(VI)	18484	4-nitro-N-[(7S)-1,2,3-trihydroxy-10-(methylsulfanyl)-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]benzamide		C₂₄H₂₀N₂O₇S	详情	详情

合成路线2

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】 Guan, J.; et al.; Antitumor agents. 185. Synthesis and biological evaluation of tridemethylthiocolchicine analogues as novel topoisomerase II inhibitors. J Med Chem 1998, 41, 11, 1956.

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)	18479	N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide	64-86-8	C₂₂H₂₅NO₆	详情	详情
(II)	18480	N-[(7S)-1,2,3-trimethoxy-10-(methylsulfanyl)-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide		C₂₂H₂₅NO₅S	详情	详情
(III)	18481	(7S)-7-amino-1,2,3-trimethoxy-10-(methylsulfanyl)-6,7-dihydrobenzo[a]heptalen-9(5H)-one		C₂₀H₂₃NO₄S	详情	详情
(IV)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(V)	18483	4-nitro-N-[(7S)-1,2,3-trimethoxy-10-(methylsulfanyl)-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]benzamide		C₂₇H₂₆N₂O₇S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The reaction of colchicin (I) with aq. HCl at 100 C gives the monodemethylated compound (II), which is treated with H2O2 at 60 C to yield the dibenzocycloheptene derivative (III). The condensation of (III) with N,N-diethylphosphoramidic acid di-tert-butyl ester (IV) by means of tetrazole affords the phosphoric acid triester (V), which is finally treated with MCPBA to provide the target phosphoric acid monoester.

参考文献中间体

合成目标

【1】 Blakey, D.C.; Davis, P.D.; Dougherty, G.J.; et al.; ZD6126: A novel vascular-targeting agent that causes selective destruction of tumor vasculature. Cancer Res 2002, 62, 24, 7247.

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)	18479	N-[(7S)-1,2,3,10-tetramethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide	64-86-8	C₂₂H₂₅NO₆	详情	详情
(II)	58655	N-[(7S)-10-hydroxy-1,2,3-trimethoxy-9-oxo-5,6,7,9-tetrahydrobenzo[a]heptalen-7-yl]acetamide		C₂₁H₂₃NO₆	详情	详情
(III)	47283	N-[(5S)-3-hydroxy-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-5-yl]acetamide		C₂₀H₂₃NO₅	详情	详情
(IV)	58656			C₁₂H₂₈NO₃P	详情	详情
(V)	47285	(5S)-5-(acetamido)-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c]cyclohepten-3-yl di(tert-butyl) phosphate		C₂₈H₄₀NO₈P	详情	详情

Extended Information