ethyl 2-[(2,3-dichloro-6-nitrobenzyl)amino]acetate -Drug Synthesis Database

【结构式】

【分子编号】29086

【品名】ethyl 2-[(2,3-dichloro-6-nitrobenzyl)amino]acetate

【CA登记号】

【分子式】C₁₁H₁₂Cl₂N₂O₄

【分子量】307.13276

【元素组成】C 43.02% H 3.94% Cl 23.09% N 9.12% O 20.84%

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：(VI)

The nitration of 1,2,3-trichlorobenzene (I) with concentrated HNO3 gives 2,3,4-trichloronitrobenzene (II), which by reaction with cuprous cyanide in hot pyridine is converted to 2,3-dichloro-6-nitrobenzonitrile (III). The reduction of (III) with borane in THF yields 2,3-dichloro-6-nitrobenzylamine (IV), which by reaction with ethyl bromoacetate (V) by means of triethylamine in refluxing dioxane affords ethyl N-(2,3-dichloro-6-nitrobenzyl)glycinate (VI). The reduction of (VI) with SnCl2 in concentrated HCl gives ethyl N-(6-amino-2,3-dichlorobenzyl)glycinate (VII), which is cyclized with cyanogen bromide (VIII) in toluene affording ethyl 5,6-dichloro-3,4-dihydro-2-(1H)-iminoquinazoline-3-acetate (IX). Finally, this compound is submitted to a new cyclization by means of triethylamine in refluxing ethanol.

参考文献中间体

合成目标

【1】 Jenks, T.A.; Beverung, W.N.Jr.; Partyka, R.A. (Bristol-Myers Squibb Co.); Preparation of 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one. CA 1137474 .

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)	29082	1,2,3-trichlorobenzene	87-61-6	C₆H₃Cl₃	详情	详情
(II)	29083	1,2,3-trichloro-4-nitrobenzene	17700-09-3	C₆H₂Cl₃NO₂	详情	详情
(III)	29084	2,3-dichloro-6-nitrobenzonitrile		C₇H₂Cl₂N₂O₂	详情	详情
(IV)	29085	(2,3-dichloro-6-nitrophenyl)methanamine	70380-49-3	C₇H₆Cl₂N₂O₂	详情	详情
(V)	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(VI)	29086	ethyl 2-[(2,3-dichloro-6-nitrobenzyl)amino]acetate		C₁₁H₁₂Cl₂N₂O₄	详情	详情
(VII)	29087	ethyl 2-[(6-amino-2,3-dichlorobenzyl)amino]acetate		C₁₁H₁₄Cl₂N₂O₂	详情	详情
(VIII)	28017	cyanic bromide；cyanogen bromide	506-68-3	CBrN	详情	详情
(IX)	29088	ethyl 2-[5,6-dichloro-2-imino-1,4-dihydro-3(2H)-quinazolinyl]acetate		C₁₂H₁₃Cl₂N₃O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The nitration of 2,3-dichlorobenzaldehyde (I) with HNO3/H2SO4 gives 2,3-dichloro-6-nitrobenzaldehyde (II), which is reduced with NaBH4 in methanol, yielding 2,3-dichloro-6-nitrobenzyl alcohol (III). The reaction of (III) with SOCl2 and TEA affords the benzyl chloride (IV), which is condensed with glycine ethyl ester (V) by means of TEA to provide the adduct (VI). The reduction of the nitro group of (VI) with SnCl2 in aq. HCl or H2 over PtO2/C in ethanol gives the expected amino derivative (VII), which is cyclized with CN-Br in toluene to yield the iminoquinazoline (VIII). Finally, this compound is further cyclized by means of TEA in water to afford the target imidazoquinazolinone.

参考文献中间体

合成目标

【1】 Lang, P.C.; Spencer, R.P.; Yeh, W.-L.; Roth, M.J. (Shire Richwood Inc.); Method for the manufacture of anagrelide. WO 0208228 .

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)	14742	2,3-dichlorobenzaldehyde	6334-18-5	C₇H₄Cl₂O	详情	详情
(II)	52800	2,3-dichloro-6-nitrobenzaldehyde		C₇H₃Cl₂NO₃	详情	详情
(III)	52801	(2,3-dichloro-6-nitrophenyl)methanol		C₇H₅Cl₂NO₃	详情	详情
(IV)	52802	1,2-dichloro-3-(chloromethyl)-4-nitrobenzene		C₇H₄Cl₃NO₂	详情	详情
(V)	10309	ethyl 2-aminoacetate; Glycine ethyl ester	459-73-4	C₄H₉NO₂	详情	详情
(VI)	29086	ethyl 2-[(2,3-dichloro-6-nitrobenzyl)amino]acetate		C₁₁H₁₂Cl₂N₂O₄	详情	详情
(VII)	29087	ethyl 2-[(6-amino-2,3-dichlorobenzyl)amino]acetate		C₁₁H₁₄Cl₂N₂O₂	详情	详情
(VIII)	29088	ethyl 2-[5,6-dichloro-2-imino-1,4-dihydro-3(2H)-quinazolinyl]acetate		C₁₂H₁₃Cl₂N₃O₂	详情	详情

Extended Information