1-(4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one -Drug Synthesis Database

【结构式】

【分子编号】41811

【品名】1-(4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one

【CA登记号】

【分子式】C₁₇H₁₄N₂O₄

【分子量】310.30924

【元素组成】C 65.8% H 4.55% N 9.03% O 20.62%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(III)

Acylation of 2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (I) with 4-nitrobenzoyl chloride (II) by means of TEA in CH2Cl2 gives 1-(4-nitrobenzoyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (III), which is hydrogenated with H2 over Raney-Ni in MeOH, yielding the corresponding amine derivative (IV). Acylation of (IV) with biphenyl-2-carboxylic acid (V) by means of oxalyl chloride in CH2Cl2 affords the expected amide (VI) which is brominated with either Br2 or CuBr2, providing the alpha-bromo ketone (VII). This ketone (VII) is cyclized with acetamidine hydrochloride (VIII) by means of K2CO3 in MeCN, furnishing a mixture of conivaptan and oxazolo[4,5-d][1]benzodiazepine compound. Finally, conivaptan is separated by column chromatography over silica gel and is treated with 4N HCl to provide the desired hydrochloride.

参考文献中间体

合成目标

【1】 Castañer, R.M.; Norman, P.; Rabasseda, X.; Leeson, P.A.; Castañer, J.; Conivaptan Hydrochloride. Drugs Fut 2000, 25, 11, 1121.
【2】 Tanaka, A.; Koshio, H.; Taniguchi, N.; Matsuhisa, A.; Sakamoto, K.; Yamazaki, A.; Yatsu, T. (Yamanouchi Pharmaceutical Co., Ltd.); Fused benzazepine deriv. and pharmaceutical compsn. containing the same. EP 0709386; JP 1995505056; US 5723606; WO 9503305 .
【3】 Koshio, H.; Taniguchi, N.; Tanaka, A.; Yatsu, T.; Matsuhisa, A.; Nonpeptide arginine vasopressin antagonists for both V1A and V2 receptors: Synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)benzanilide derivatives and 4'-(5,6-dihydro-4H-thiazolo[5,4-d][1]benzoaze. Chem Pharm Bull 2000, 48, 1, 21.

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)	41810	1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₀H₁₁NO	详情	详情
(II)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情
(III)	41811	1-(4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₄N₂O₄	详情	详情
(IV)	41812	1-(4-aminobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₆N₂O₂	详情	详情
(V)	18505	[1,1'-biphenyl]-2-carboxylic acid	947-84-2	C₁₃H₁₀O₂	详情	详情
(VI)	41813	N-[4-[(5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide		C₃₀H₂₄N₂O₃	详情	详情
(VII)	41814	N-[4-[(4-bromo-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide		C₃₀H₂₃BrN₂O₃	详情	详情
(VIII)	15866	ethanimidamide		C₂H₆N₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 MatsuhisaA，Taniguchi N,et al.2000.Nonpeptide arginine vasopressin antagonists for both VIA and V2 receptors: synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d] [1] benzazepine-6-carbonyl) benzanilide derivatives and 4’-(5,6-dihydro-4H-thiazolo[5,4-d] [1] benzazepint-6-carbonyl) benzanilide derivative. Chem Pharm Bull, 48, 21～31 MatsuhisaA，Taniguchi N,et al.2000.Nonpeptide arginine vasopressin antagonists for both VIA and V2 receptors: synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d] [1] benzazepine-6-carbonyl) benzanilide derivatives and 4’-(5,6-dihydro-4H-thiazolo[5,4-d] [1] benzazepint-6-carbonyl) benzanilide derivative. Chem Pharm Bull, 48, 21～31 MatsuhisaA，Taniguchi N,et al.2000.Nonpeptide arginine vasopressin antagonists for both VIA and V2 receptors: synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d] [1] benzazepine-6-carbonyl) benzanilide derivatives and 4’-(5,6-dihydro-4H-thiazolo[5,4-d] [1] benzazepint-6-carbonyl) benzanilide derivative. Chem Pharm Bull, 48, 21～31

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（V）	41814	N-[4-[(4-bromo-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide		C₃₀H₂₃BrN₂O₃	详情	详情
(I)	41811	1-(4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₄N₂O₄	详情	详情
(II)	41812	1-(4-aminobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₆N₂O₂	详情	详情
(III)	18506	[1,1'-biphenyl]-2-carbonyl chloride		C₁₃H₉ClO	详情	详情
(IV)	41813	N-[4-[(5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]phenyl][1,1'-biphenyl]-2-carboxamide		C₃₀H₂₄N₂O₃	详情	详情
(VI)	66210	N-(4-(2-methyl-1,4,5,6-tetrahydrobenzo[b]imidazo[4,5-d]azepine-6-carbonyl)phenyl)-[1,1'-biphenyl]-2-carboxamide；Conivaptan	210101-16-9	C₃₂H₂₆N₄O₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Tsunoda T,Yamazaki A.et al.2003.vasopressin antagonist. Org Ptoc Res Dev,7 1 883~887 MatsuhisaA，Taniguchi N,et al.2000.Nonpeptide arginine vasopressin antagonists for both VIA and V2 receptors: synthesis and pharmacological properties of 4'-(1,4,5,6-tetrahydroimidazo[4,5-d] [1] benzazepine-6-carbonyl) benzanilide derivatives and 4’-(5,6-dihydro-4H-thiazolo[5,4-d] [1] benzazepint-6-carbonyl) benzanilide derivative. Chem Pharm Bull, 48, 21～31

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	41811	1-(4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one	C₁₇H₁₄N₂O₄	详情	详情
(II)	66211	4-bromo-1-(4-nitrobenzoyl)-3,4-dihydro-1H-benzo[b]azepin-5(2H)-one	C₁₇H₁₃BrN₂O₄	详情	详情
(III)	41818	[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl](4-nitrophenyl)methanone	C₁₉H₁₆N₄O₃	详情	详情
(IV)	41819	(4-aminophenyl)[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl]methanone	C₁₉H₁₈N₄O	详情	详情
(VII)	18506	[1,1'-biphenyl]-2-carbonyl chloride	C₁₃H₉ClO	详情	详情

Extended Information