(4S)-9-[(Chlorocarbonyl)oxy]-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline -Drug Synthesis Database

【结构式】

【分子编号】10820

【品名】(4S)-9-[(Chlorocarbonyl)oxy]-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline

【CA登记号】

【分子式】C₂₃H₁₉ClN₂O₆

【分子量】454.86644

【元素组成】C 60.73% H 4.21% Cl 7.79% N 6.16% O 21.1%

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)

A more complete synthesis for CPT-11 has been reported: The reaction of camptothecin (I) with propionaldehyde and FeSO4 in water gives 7-ethylcamptothecin (II), which is oxidized with H2O2 in hot acetic acid yielding 7-ethylcamptothecin 1-oxide (III). The isomerization of (III) with UV light (high-pressure Hg lamp) in dioxane-1 N H2SO4 affords 7-ethyl-10-hydroxycamptothecin (IV), which is treated with phosgene and triethylamine in dioxane to give the corresponding chlorocarbonyl derivative (V). Finally, this compound is condensed with 4-piperidinopiperidine (VI) by means of pyridine in dichloromethane.

参考文献中间体

合成目标

【1】 Nokata, K.-I.; Furuta, T.; Yokokura, T.; Okajima, S.; Sawada, S.; Sugino, E.; Miyasaka, T.; Aiyama, R.; Yamaguchi, K.; Synthesis and antitumor activity of 20(S)-camptothecin derivatives: Carbamate-linked, water-soluble derivatives of 7-ethyl-10-hydroxycamptothecin. Chem Pharm Bull 1991, 39, 6, 1446-54.

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)	10816	Camptothecin; (4S)-4-Ethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 4-et-4-hydroxy-1,12-dihydro-4h-2-oxa-6,12a-diaza-dibenzo(b,h)fluorene-3,13-dione	7689-03-4	C₂₀H₁₆N₂O₄	详情	详情
(II)	10817	(4S)-4,11-Diethyl-4-hydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 7-Ethylcamptothecin		C₂₂H₂₀N₂O₄	详情	详情
(III)	10818	(4S)-4,11-Diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-6-ium-6-olate; 7-Ethylcamptothecin 1-oxide		C₂₂H₂₀N₂O₅	详情	详情
(IV)	10819	(4S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 7-Ethyl-10-hydroxycamptothecin		C₂₂H₂₀N₂O₅	详情	详情
(V)	10820	(4S)-9-[(Chlorocarbonyl)oxy]-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline		C₂₃H₁₉ClN₂O₆	详情	详情
(VI)	10821	4-Piperidinopiperidine	4897-50-1	C₁₀H₂₀N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The reaction of 7-ethyl-10-hydroxycamptothecin (I) with phosgene gives 7-ethyl-10-(chlorocarbonyloxy)camptothecin (II), which is then condensed with 4-(1-piperidyl)piperidine.

参考文献中间体

合成目标

【1】 Miyasaka, T.; Mutai, M.; Nokata, K.; Sawada, S.; Sugino, E. (Yakult Honsha Co., Ltd.); New camptothecin derivs. and process for preparing same. EP 0137145; JP 1985019790 .
【2】 Davis, P.D. (Angiogene Pharmaceuticals Ltd.); Benzimidazole vascular damaging agents. EP 1140078; WO 0041669 .

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)	10819	(4S)-4,11-Diethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; 7-Ethyl-10-hydroxycamptothecin		C₂₂H₂₀N₂O₅	详情	详情
(II)	10820	(4S)-9-[(Chlorocarbonyl)oxy]-4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline		C₂₃H₁₉ClN₂O₆	详情	详情
(III)	10821	4-Piperidinopiperidine	4897-50-1	C₁₀H₂₀N₂	详情	详情

Extended Information