(4-aminophenyl)[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl]methanone -Drug Synthesis Database

【结构式】

【分子编号】41819

【品名】(4-aminophenyl)[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl]methanone

【CA登记号】

【分子式】C₁₉H₁₈N₄O

【分子量】318.37828

【元素组成】C 71.68% H 5.7% N 17.6% O 5.03%

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：(XV)

The bromination of 1-(p-toluenesulfonyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one (IX) with Br2 in CHCl3 gives the alpha-bromo ketone (X), which is cyclized with acetamidine hydrochloride (VIII) by means of K2CO3, yielding the expected imidazo-benzazepine (XI). This compound is detosylated with hot H2SO4 to provide 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine (XII). Acylation of (XII) with 4-nitroben-zoic acid (XIII) by means of pyridine in either hot MeCN or DMF affords the 6-(4-nitro-benzoyl) derivative (XIV), which is reduced with H2 and Raney-Ni in MeOH to the corres-ponding 6-(4-aminobenzoyl) compound (XV). Finally, this compound is condensed with biphenyl-2-carbonyl chloride (XVI) [ obtained by treatment of biphenyl-2-carboxylic acid (V) with oxalyl chloride in CH2Cl2/DMF] by means of pyridine in acetonitrile and treated with 4N HCl.

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】 Yamazaki, A.; Tanaka, A.; Tsunoda, T. (Yamanouchi Pharmaceutical Co., Ltd.); Novel preparation method of condensed benzazepine derivs.. JP 1996198879 .

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)	18505	[1,1'-biphenyl]-2-carboxylic acid	947-84-2	C₁₃H₁₀O₂	详情	详情
(VIII)	15866	ethanimidamide		C₂H₆N₂	详情	详情
(IX)	14763	1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₇NO₃S	详情	详情
(X)	41815	4-bromo-1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₆BrNO₃S	详情	详情
(XI)	41816	2-methyl-6-[(4-methylphenyl)sulfonyl]-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine		C₁₉H₁₉N₃O₂S	详情	详情
(XII)	41817	2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine	318237-73-9	C₁₂H₁₃N₃	详情	详情
(XIII)	18119	4-nitrobenzoic acid; p-nitrobenzoic acid	62-23-7	C₇H₅NO₄	详情	详情
(XIV)	41818	[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl](4-nitrophenyl)methanone		C₁₉H₁₆N₄O₃	详情	详情
(XV)	41819	(4-aminophenyl)[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl]methanone		C₁₉H₁₈N₄O	详情	详情
(XVI)	18506	[1,1'-biphenyl]-2-carbonyl chloride		C₁₃H₉ClO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

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

合成路线3

该中间体在本合成路线中的序号：(X)

参考文献中间体

合成目标

【1】 Tsunoda T, Tanaka A, et al.2004.Anew synthetic route to YM087, an argirune asopressin antagonist.Heterocycles, 63: 1113---1122

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）	14763	1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₇NO₃S	详情	详情
(I)	11161	methyl 2-aminobenzoate; Methyl anthranilate	134-20-3	C₈H₉NO₂	详情	详情
(II)	66212	methyl 2-(4-methylphenylsulfonamido)benzoate		C₁₅H₁₅NO₄S	详情	详情
(III)	66213	methyl 2-(N-(3-cyanopropyl)-4-methylphenylsulfonamido)benzoate		C₁₉H₂₀N₂O₄S	详情	详情
(IV)	66214	4-ethynyl-1-tosyl-3,4-dihydro-1H-benzo[b]azepin-5(2H)-one		C₁₉H₁₇N₂O₃S	详情	详情
(VI)	41815	4-bromo-1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₆BrNO₃S	详情	详情
(VII)	41816	2-methyl-6-[(4-methylphenyl)sulfonyl]-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine		C₁₉H₁₉N₃O₂S	详情	详情
(VIII)	41817	2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine	318237-73-9	C₁₂H₁₃N₃	详情	详情
(IX)	41818	[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl](4-nitrophenyl)methanone		C₁₉H₁₆N₄O₃	详情	详情
(X)	41819	(4-aminophenyl)[2-methyl-4,5-dihydroimidazo[4,5-d][1]benzazepin-6(1H)-yl]methanone		C₁₉H₁₈N₄O	详情	详情
(XII)	18941	p-nitrobenzoyl chloride; 4-nitrobenzoyl chloride	122-04-3	C₇H₄ClNO₃	详情	详情

Extended Information