6-(2-chlorophenyl)-8-nitro-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepin-1-one -Drug Synthesis Database

【结构式】

【分子编号】30373

【品名】6-(2-chlorophenyl)-8-nitro-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepin-1-one

【CA登记号】

【分子式】C₁₇H₁₁ClN₄O₃

【分子量】354.7522

【元素组成】C 57.56% H 3.13% Cl 9.99% N 15.79% O 13.53%

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：(I)

The condensation of 6-(2-chlorophenyl)-1,2-dihydro-8-nitro-1H,4H-imidazo[1,2-a][1,4]benzodiazepin-1-one (I) with 1-(dimethoxymethyl)-4-methylpiperazine (II) gives the free base of loprazolam (III), which is then treated with methanesulfonic acid.

参考文献中间体

合成目标

【1】 Prost-Marechal, J. (Aventis Pharma SA); Imidazobenzodiazepines. DE 3211243; GB 2095674; JP 57169483 .

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)	30373	6-(2-chlorophenyl)-8-nitro-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepin-1-one		C₁₇H₁₁ClN₄O₃	详情	详情
(II)	30374	methoxy(4-methyl-1-piperazinyl)methyl methyl ether; 1-(dimethoxymethyl)-4-methylpiperazine		C₈H₁₈N₂O₂	详情	详情
(III)	30375	6-(2-chlorophenyl)-2-[(Z)-(4-methyl-1-piperazinyl)methylidene]-8-nitro-1H-imidazo[1,2-a][1,4]benzodiazepin-1(4H)-one		C₂₃H₂₁ClN₆O₃	详情	详情
(IV)	30376	methanesulfonic acid	75-75-2	CH₄O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

The reaction of 5-(2-chlorophenyl)-7-nitro-3H-1,4-benzodiazepin-2-thione (I) with glycine (A) by means of Na2CO3 in refluxing ethanol-water gives 2-carboxymethylamino-7-nitro-5-(2-chlorophenyl)-3H-1,4-benzodiazepine (II), which is cyclized by means of dicyclohexylcarbodiimide in methylene chloride to afford 8-nitro-(2-chlorophenyl)-1,2-dihydro-1H,4H-imidazo[1,2-a][1,4]benzodiazepin-1-one (III). The reaction of (III) with dimethylformamide diethylacetal (B) by means of triethylamine in benzene yields 8-nitro-2-(dimethylaminomethylene)-6-(2-chlorophenyl)-1,2-dihydro-1H,4H-imidazo[1,2a][1,4]benzodiazepin-1-one (IV), which is treated with N-methylpiperazine (C) in refluxing toluene to produce 8-nitro-(2-chlorophenyl)-2-(N-methylpiperazin-1-ylmethylene)-1,2-dihydro-1H,4H-imidazo [1,2-a][1,4]benzodiazepin-1-one (V). This compound is finally treated with methanesulfonic acid.

参考文献中间体

合成目标

【1】 Taylor, J.B.; Harrison D.R.; 1,2-Dihydro-6-phenyl-1H,4H-imidazobenzodiazepin-1-ones. US 4044142 .
【2】 Ager, J.R.; et al.; Central nervous system activity of a novel class of annelated 1,4-benzodiazwpines, aminomethylene-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepin-1-ones. J Med Chem 1977, 20, 8, 1035-41.
【3】 Thorpe, P.J.; Castaner, J.; Blancafort, P.; Serradell, M.N.; RU-31,158. Drugs Fut 1980, 5, 3, 144.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40922	N,N'-dicyclohexylurea	2387-23-7	C₁₃H₂₄N₂O	详情	详情
(A)	20436	glycine	56-40-6	C₂H₅NO₂	详情	详情
(B)	31457	N-(diethoxymethyl)-N,N-dimethylamine; diethoxy-N,N-dimethylmethanamine	1188-33-6	C₇H₁₇NO₂	详情	详情
(I)	32632	5-(2-chlorophenyl)-7-nitro-1,3-dihydro-2H-1,4-benzodiazepine-2-thione		C₁₅H₁₀ClN₃O₂S	详情	详情
(II)	32633	2-[[5-(2-chlorophenyl)-7-nitro-3H-1,4-benzodiazepin-2-yl]amino]acetic acid		C₁₇H₁₃ClN₄O₄	详情	详情
(III)	30373	6-(2-chlorophenyl)-8-nitro-2,4-dihydro-1H-imidazo[1,2-a][1,4]benzodiazepin-1-one		C₁₇H₁₁ClN₄O₃	详情	详情
(IV)	32634	6-(2-chlorophenyl)-2-[(Z)-(dimethylamino)methylidene]-8-nitro-1H-imidazo[1,2-a][1,4]benzodiazepin-1(4H)-one		C₂₀H₁₆ClN₅O₃	详情	详情
(V)	30375	6-(2-chlorophenyl)-2-[(Z)-(4-methyl-1-piperazinyl)methylidene]-8-nitro-1H-imidazo[1,2-a][1,4]benzodiazepin-1(4H)-one		C₂₃H₂₁ClN₆O₃	详情	详情
(C)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情

Extended Information