7-chloro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one -Drug Synthesis Database

【结构式】

【分子编号】33004

【品名】7-chloro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one

【CA登记号】

【分子式】C₁₀H₁₀ClNO

【分子量】195.64824

【元素组成】C 61.39% H 5.15% Cl 18.12% N 7.16% O 8.18%

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：(IX)

5-Chloro-2-nitrobenzoic acid (I) was converted into methyl ester (II) using dimethyl sulfate and K2CO3 in acetone. The nitro group of (II) was then reduced with SnCl2 to afford aniline (III), which was protected as the p-toluenesulfonamide (IV) with tosyl chloride in pyridine. Alkylation of (IV) with ethyl 4-bromobutyrate (V) yielded diester (VI). Subsequent Dieckmann cyclization of (VI) in the presence of potassium tert-butoxide provided benzazepinone (VIIa-b) as a mixture of ethyl and methyl esters, which was decarboxylated to (VIII) by heating with HCl in AcOH. Deprotection of the tosyl group of (VIII) was carried out in hot polyphosphoric acid. The resulting benzazepinone (IX) was condensed with 2-methyl-4-nitrobenzoyl chloride (X) to give amide (XI). After reduction of the nitro group of (XI) to the corresponding aniline (XII), condensation with 2-methylbenzoyl chloride (XIII) provided diamide (XIV). Finally, ketone reduction in (XIV) by means of NaBH4 led to the target compound.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Silvestre, J.S.; Castañer, J.; Bayes, M.; Tolvaptan. Drugs Fut 2002, 27, 4, 350.
【2】 Kondo, K.; Yamashita, H.; Ogawa, H.; et al.; 7-Chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-41061): A potent, orally active nonpeptide arginine vasopressin V2 receptor antagonist. Bioorg Med Chem 1999, 7, 8, 1743.
【3】 Yabuuchi, Y.; Kora, S.; Tanaka, M.; Miyamoto, H.; Komatsu, H.; Kondo, K.; Yamashita, H.; Tominaga, M.; Ogawa, H.; Nakaya, K. (Otsuka Pharmaceutical Co., Ltd.); Benzoheterocyclic cpds. US 5985869 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VIIa)	33001	methyl 7-chloro-1-[(4-methylphenyl)sulfonyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate		C₁₉H₁₈ClNO₅S	详情	详情
(VIIb)	33002	ethyl 7-chloro-1-[(4-methylphenyl)sulfonyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine-4-carboxylate		C₂₀H₂₀ClNO₅S	详情	详情
(I)	32996	5-chloro-2-nitrobenzoic acid	2516-95-2	C₇H₄ClNO₄	详情	详情
(II)	32997	methyl 5-chloro-2-nitrobenzoate	51282-49-6	C₈H₆ClNO₄	详情	详情
(III)	32998	methyl 2-amino-5-chlorobenzoate	5202-89-1	C₈H₈ClNO₂	详情	详情
(IV)	32999	methyl 5-chloro-2-[[(4-methylphenyl)sulfonyl]amino]benzoate		C₁₅H₁₄ClNO₄S	详情	详情
(V)	11263	ethyl 4-bromobutanoate; Ethyl 4-bromobutyrate	2969-81-5	C₆H₁₁BrO₂	详情	详情
(VI)	33000	methyl 5-chloro-2-[(4-ethoxy-4-oxobutyl)[(4-methylphenyl)sulfonyl]amino]benzoate		C₂₁H₂₄ClNO₆S	详情	详情
(VIII)	33003	7-chloro-1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₆ClNO₃S	详情	详情
(IX)	33004	7-chloro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₀H₁₀ClNO	详情	详情
(X)	33005	2-methyl-4-nitrobenzoyl chloride		C₈H₆ClNO₃	详情	详情
(XI)	33006	7-chloro-1-(2-methyl-4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₈H₁₅ClN₂O₄	详情	详情
(XII)	33007	1-(4-amino-2-methylbenzoyl)-7-chloro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₈H₁₇ClN₂O₂	详情	详情
(XIII)	14770	2-methylbenzoyl chloride; o-Toluoyl chloride	933-88-0	C₈H₇ClO	详情	详情
(XIV)	33008	N-[4-[(7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methylbenzamide		C₂₆H₂₃ClN₂O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

参考文献中间体

合成目标

【1】 Kondo K, Ogawa H, Yamashita H, et al.1999.7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoyl-amino) benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine (OPC-41061): A potent, orally active nonpeptide arginine vasopressin V2 receptor antagonist. Bioorg Med Chem, 7: 1743～1754.

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)	32996	5-chloro-2-nitrobenzoic acid	2516-95-2	C₇H₄ClNO₄	详情	详情
(II)	32999	methyl 5-chloro-2-[[(4-methylphenyl)sulfonyl]amino]benzoate		C₁₅H₁₄ClNO₄S	详情	详情
(III)	33000	methyl 5-chloro-2-[(4-ethoxy-4-oxobutyl)[(4-methylphenyl)sulfonyl]amino]benzoate		C₂₁H₂₄ClNO₆S	详情	详情
(IV)	33003	7-chloro-1-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₇H₁₆ClNO₃S	详情	详情
(V)	33004	7-chloro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₀H₁₀ClNO	详情	详情
(VI)	33006	7-chloro-1-(2-methyl-4-nitrobenzoyl)-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₈H₁₅ClN₂O₄	详情	详情
(VII)	33007	1-(4-amino-2-methylbenzoyl)-7-chloro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one		C₁₈H₁₇ClN₂O₂	详情	详情
(VIII)	33008	N-[4-[(7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methylbenzamide		C₂₆H₂₃ClN₂O₃	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】 Torisawa Y, Furuta T, Nishi T, et al.2007.Aminocarbonylation route to Tolvaptan. Bioorg Med Chem Lett, 17: 6455～6458.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	33004	7-chloro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-one	C₁₀H₁₀ClNO	详情	详情
(II)	67460	N-(4-bromo-3-methylphenyl)-2-methylbenzamide	C₁₅H₁₄BrNO	详情	详情
(III)	33008	N-[4-[(7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]-3-methylphenyl]-2-methylbenzamide	C₂₆H₂₃ClN₂O₃	详情	详情

Extended Information