1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one -Drug Synthesis Database

【结构式】

【分子编号】18498

【品名】1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one

【CA登记号】

【分子式】C₉H₁₀N₂O

【分子量】162.19128

【元素组成】C 66.65% H 6.21% N 17.27% O 9.86%

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：(IV)

Condensation of benzodiazepinone (IV) with 4-nitrobenzoyl chloride (V) afforded amide (VI), which was alkylated with ethyl bromoacetate in the presence of NaH to give (VII). The nitro group of (VII) was reduced to aniline (VIII) using Fe and AcOH. Subsequent coupling of (VIII) with the acid chloride generated from biphenyl carboxylic acid (III) and oxalyl chloride produced the corresponding amide (IX). The ester group of (IX) was then hydrolyzed with NaOH, and the resulting carboxylic acid (X) was finally condensed with N-methylpiperazine (XI) using 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole as the coupling reagents.

参考文献中间体

合成目标

【1】 Hosogai, N.; Tanaka, H.; Tomita, M.; Ohkawa, T.; Hemmi, K.; Setoi, H.; Zenkoh, O.; Synthesis and characterization of orally active nonpeptide vasopressin V2 receptor antagonists. Chem Pharm Bull 1999, 47, 4, 501.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	16640	Ethyl 2-bromoacetate; Ethyl bromoacetate	105-36-2	C₄H₇BrO₂	详情	详情
(III)	16915	4'-methyl[1,1'-biphenyl]-2-carboxylic acid	7148-03-0	C₁₄H₁₂O₂	详情	详情
(IV)	18498	1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one		C₉H₁₀N₂O	详情	详情
(V)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(VI)	27975	5-(4-nitrobenzoyl)-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one		C₁₆H₁₃N₃O₄	详情	详情
(VII)	27976	ethyl 2-[5-(4-nitrobenzoyl)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl]acetate		C₂₀H₁₉N₃O₆	详情	详情
(VIII)	27977	ethyl 2-[5-(4-aminobenzoyl)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl]acetate		C₂₀H₂₁N₃O₄	详情	详情
(IX)	27978	ethyl 2-[5-(4-[[(4'-methyl[1,1'-biphenyl]-2-yl)carbonyl]amino]benzoyl)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl]acetate		C₃₄H₃₁N₃O₅	详情	详情
(X)	27979	2-[5-(4-[[(4'-methyl[1,1'-biphenyl]-2-yl)carbonyl]amino]benzoyl)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl]acetic acid		C₃₂H₂₇N₃O₅	详情	详情
(XI)	10061	1-Methylpiperazine; 1-Methyl piperazine; N-Methylpiperazine	109-01-3	C₅H₁₂N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Alkylation of benzodiazepinone (I) with 3-(chloromethyl)- pyridine (II) in the presence of NaH gave the 1-substituted benzodiazepinone (III). Reduction of the amide group of (III) with borane in THF afforded benzodiazepine (IV). Subsequent condensation with 4-nitrobenzoyl chloride (V) gave nitrobenzamide (VI), which was reduced to amine (VII) by hydrogenation in the presence of Pd/C. This compound was coupled with acid chloride (IX) (prepared by treatment of 2-phenylbenzoic acid (VIII) with oxalyl chloride) to yield the title compound.

参考文献中间体

合成目标

【1】 Matsuhisa, A.; Koshio, H.; Sakamoto, K.; Taniguchi, N.; Yatsu, T.; Tanaka, A.; Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: Synthesis and pharmacological properties of 2-phenyl-4'-(2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-1-carbonyl)benzanilide derivatives. Chem Pharm Bull 1998, 46, 10, 1566.

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)	18498	1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one		C₉H₁₀N₂O	详情	详情
(II)	15793	3-(Chloromethyl)pyridine	3099-31-8	C₆H₆ClN	详情	详情
(III)	18500	1-(3-pyridinylmethyl)-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one		C₁₅H₁₅N₃O	详情	详情
(IV)	18501	1-(3-pyridinylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine		C₁₅H₁₇N₃	详情	详情
(V)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(VI)	18503	(4-nitrophenyl)[5-(3-pyridinylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl]methanone		C₂₂H₂₀N₄O₃	详情	详情
(VII)	18504	(4-aminophenyl)[5-(3-pyridinylmethyl)-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-1-yl]methanone		C₂₂H₂₂N₄O	详情	详情
(VIII)	18505	[1,1'-biphenyl]-2-carboxylic acid	947-84-2	C₁₃H₁₀O₂	详情	详情
(IX)	18506	[1,1'-biphenyl]-2-carbonyl chloride		C₁₃H₉ClO	详情	详情

Extended Information