1,4-bis(benzyloxy)-5,8-dichloroanthra-9,10-quinone -Drug Synthesis Database

【结构式】

【分子编号】27774

【品名】1,4-bis(benzyloxy)-5,8-dichloroanthra-9,10-quinone

【CA登记号】

【分子式】C₂₈H₁₈Cl₂O₄

【分子量】489.35392

【元素组成】C 68.72% H 3.71% Cl 14.49% O 13.08%

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：(II)

Treatment of 1,4-dichloro-5,8-dihydroxy-9,10-anthracenedione (I) with K2CO3 and benzyl bromide gives the benzyl ether (II) in refluxing acetone, which, followed by treatment with 2-[(2-hydrazinoethyl)amino]ethanol in anhydrous Me2SO, gives product (III). Treatment of product (III) with excess [(2-aminoethyl)amino]methane in refluxing pyridine gives the «two armed» compound, which, followed by treatment with Pearlman's catalyst in glacial AcOH, gives the target compound CI-937.

参考文献中间体

合成目标

【1】 Proc Amer Assoc Cancer Res 1984, 25, 1, 352.
【2】 Hoshi, A.; CI-937 and CI-942. Drugs Fut 1986, 11, 3, 179.
【3】 Showalter, H.D.H.; Johnson, J.L.; Werbel, L.M.; Leopold, W.R.; Jackson, R.C.; Elslager, E.F.; 5-[(Aminoalkyl)amino]-substituted anthra[1, 9-cd]pyrazol-6(2H)-ones as novel anticancer agents. Synthesis and biological evaluation. J Med Chem 1984, 27, 3, 253-5.

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)	27775	2-[(2-hydrazinoethyl)amino]-1-ethanol		C₄H₁₃N₃O	详情	详情
(B)	27777	N-(2-aminoethyl)-N-methylamine	109-81-9	C₃H₁₀N₂	详情	详情
(I)	27773	1,4-dichloro-5,8-dihydroxyanthra-9,10-quinone		C₁₄H₆Cl₂O₄	详情	详情
(II)	27774	1,4-bis(benzyloxy)-5,8-dichloroanthra-9,10-quinone		C₂₈H₁₈Cl₂O₄	详情	详情
(III)	27776	7,10-bis(benzyloxy)-5-chloro-2-[2-[(2-hydroxyethyl)amino]ethyl]dibenzo[cd,g]indazol-6(2H)-one		C₃₂H₂₈ClN₃O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Treatment of 1,4-di(benzyloxy)-5,8-dichloro-9,10-dihydro-9,10-anthracenedione (I) with CuCN in hot DMA results in the desired monosubstituted derivative (II). Subsequent basic hydrolysis of the nitrile group of (II) leads to carboxylic acid (III). After conversion of (III) into the corresponding acid chloride (IV) by means of PCl5, reaction with 2-(dimethylamino)ethylhydrazine (V) produces the tetracyclic compound (VI). Displacement of the remaining chloride of (VI) with 2-(dimethylamino)ethylamine (VII) in DMA then gives (VIII). The protecting benzyl groups of (VIII) are finally removed with trifluoroacetic acid to furnish the title compound.

参考文献中间体

合成目标

【1】 Stefanska, B.; Arciemiuk, M.; Bontemps-Gracz, M.M.; Dzieduszycka, M.; Kupiec, A.; Martelli, S.; Borowski, E.; Synthesis and biological evaluation of 2,7-dihydro-3H-dibenzo[de,h]cinnoline-3,7-dione derivatives, a novel group of anticancer agents active on a multidrug resistant cell line. Bioorg Med Chem 2003, 11, 4, 561.

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)	27774	1,4-bis(benzyloxy)-5,8-dichloroanthra-9,10-quinone		C₂₈H₁₈Cl₂O₄	详情	详情
(II)	63403	5,8-bis(benzyloxy)-4-chloro-9,10-dioxo-9,10-dihydro-1-anthracenecarbonitrile		C₂₉H₁₈ClNO₄	详情	详情
(III)	63404	5,8-bis(benzyloxy)-4-chloro-9,10-dioxo-9,10-dihydro-1-anthracenecarboxylic acid		C₂₉H₁₉ClO₆	详情	详情
(IV)	63405	5,8-bis(benzyloxy)-4-chloro-9,10-dioxo-9,10-dihydro-1-anthracenecarbonyl chloride		C₂₉H₁₈Cl₂O₅	详情	详情
(V)	41186	N-(2-hydrazinoethyl)-N,N-dimethylamine; 2-hydrazino-N,N-dimethyl-1-ethanamine		C₄H₁₃N₃	详情	详情
(VI)	63406	8,11-bis(benzyloxy)-6-chloro-2-[2-(dimethylamino)ethyl]-3H-dibenzo[de,h]cinnoline-3,7(2H)-dione		C₃₃H₂₈ClN₃O₄	详情	详情
(VII)	14881	N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine	108-00-9	C₄H₁₂N₂	详情	详情
(VIII)	63407	8,11-bis(benzyloxy)-2-[2-(dimethylamino)ethyl]-6-{[2-(dimethylamino)ethyl]amino}-3H-dibenzo[de,h]cinnoline-3,7(2H)-dione		C₃₇H₃₉N₅O₄	详情	详情

Extended Information