{7-chloro-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinolin-8-yl}methanol -Drug Synthesis Database

【结构式】

【分子编号】54875

【品名】{7-chloro-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinolin-8-yl}methanol

【CA登记号】

【分子式】C₁₈H₂₂ClN₃O₃

【分子量】363.8438

【元素组成】C 59.42% H 6.09% Cl 9.74% N 11.55% O 13.19%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(XV)

In a different strategy, the dioxinoquinoline system (XII) was prepared by acylation of amino ketone (X) with methyl malonyl chloride (XI), followed by intramolecular Knoevenagel condensation of the intermediate keto malonamide. Chlorination of (XII) with POCl3 afforded the dichloro derivative (XIII), which was subsequently condensed with N-methylpiperazine (IX) to give (XIV). Reduction of the ester group of (XIV) by means of DIBAL provided alcohol (XV). Replacement of the 7-chloro of (XV) by an iodide group required previous oxidation of (XV) to the more reactive aldehyde (XVI). Treatment of (XVI) with NaI and HCl led to the corresponding iodo aldehyde, which was further reduced to alcohol (XVII) using NaBH4.

参考文献中间体

合成目标

【1】 Fang, F.G.; Xie, S.; Lowery, M.W. (GlaxoSmithKline Inc.); Intermediates in pharmaceutical camptothecin preparation. WO 9529917 .
【2】 Huie, E.M.; Fang, F.G.; Xie, S.; Comins, D.L. (GlaxoSmithKline Inc.; North Carolina State University); Preparation of a camptothecin deriv. by intramolecular cyclisation. WO 9529919 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IX)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情
(X)	54870	1-(7-amino-2,3-dihydro-1,4-benzodioxin-6-yl)-2-chloro-1-ethanone		C₁₀H₁₀ClNO₃	详情	详情
(XI)	50272	Malonic acid monomethyl ester chloride; Methyl (chloroformyl)acetate; Methyl malonyl chloride ;Methyl 3-chloro-3-oxopropionate	37517-81-0	C₄H₅ClO₃	详情	详情
(XII)	54872	methyl 9-(chloromethyl)-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylate		C₁₄H₁₂ClNO₅	详情	详情
(XIII)	54873	methyl 7-chloro-9-(chloromethyl)-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylate		C₁₄H₁₁Cl₂NO₄	详情	详情
(XIV)	54874	methyl 7-chloro-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylate		C₁₉H₂₂ClN₃O₄	详情	详情
(XV)	54875	{7-chloro-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinolin-8-yl}methanol		C₁₈H₂₂ClN₃O₃	详情	详情
(XVI)	54876	7-chloro-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carbaldehyde		C₁₈H₂₀ClN₃O₃	详情	详情
(XVII)	54877	{7-iodo-9-[(4-methyl-1-piperazinyl)methyl]-2,3-dihydro[1,4]dioxino[2,3-g]quinolin-8-yl}methanol		C₁₈H₂₂IN₃O₃	详情	详情

Extended Information