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【结 构 式】

【分子编号】29088

【品名】ethyl 2-[5,6-dichloro-2-imino-1,4-dihydro-3(2H)-quinazolinyl]acetate

【CA登记号】

【 分 子 式 】C12H13Cl2N3O2

【 分 子 量 】302.15964

【元素组成】C 47.7% H 4.34% Cl 23.47% N 13.91% O 10.59%

与该中间体有关的原料药合成路线共 3 条

合成路线1

该中间体在本合成路线中的序号:(IX)

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.

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:(IX)

The reaction of 3-chloroaniline (X) with choral hydrate (XI) and hydroxylamine gives isonitroso-3-chloroacetanilide (XII), which is cyclized by means of H2SO4 to 4-chloroisatin (XIII). Chlorination of (XIII) with SO2Cl2 affords 4,5-dichloroisatin (XIV), which is oxidized with H2O2 yielding 5,6-dichloroanthranilic acid (XV). The reduction of (XV) with borane in THF gives 6-amino-2,3-dichlorobenzyl alcohol (XVI), which by reaction with SOCl2 in benzene is converted to 6-amino-2,3-dichlorobenzyl chloride (XVII). This compound is condensed with ethyl glycinate (XVIII) by means of triethylamine in refluxing methylene chloride to give 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.

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
(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
(X) 25239 3-chloroaniline; 3-chlorophenylamine 108-42-9 C6H6ClN 详情 详情
(XI) 14018 2,2,2-Trichloro-1,1-ethanediol; Chloral hydrate 302-17-0 C2H3Cl3O2 详情 详情
(XII) 29089 N-(3-chlorophenyl)-2-(hydroxyimino)acetamide C8H7ClN2O2 详情 详情
(XIII) 29090 4-chloro-1H-indole-2,3-dione C8H4ClNO2 详情 详情
(XIV) 29091 4,5-dichloro-1H-indole-2,3-dione C8H3Cl2NO2 详情 详情
(XV) 29092 6-amino-2,3-dichlorobenzoic acid C7H5Cl2NO2 详情 详情
(XVI) 29093 (6-amino-2,3-dichlorophenyl)methanol C7H7Cl2NO 详情 详情
(XVII) 29094 3,4-dichloro-2-(chloromethyl)aniline C7H6Cl3N 详情 详情
(XVIII) 10309 ethyl 2-aminoacetate; Glycine ethyl ester 459-73-4 C4H9NO2 详情 详情

合成路线3

该中间体在本合成路线中的序号:(VIII)

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.

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