160129-45-3Relevant academic research and scientific papers
Halogenated method of aromatic compound
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Paragraph 0062-0065, (2021/11/10)
The invention belongs to the field of organic synthesis, and particularly relates to synthesis of aromatic halogens, in particular to arylamine. The invention discloses a synthesis method of a corresponding ortho-halogenated product from aromatic compounds such as carbazole and phenol. The method comprises the following steps: adding a metal sulfonate salt catalyst, aromatic amine, carbazole, phenol and other hydrogen - heteroatom-containing aromatic compound reaction substrates, a halogenation reagent and a reaction solvent at a specific reaction temperature. After the drying agent is dried, the yield of the reaction product and the nuclear magnetic characterization determining structure are determined by column chromatography. The reaction product yield is determined by gas chromatography. By adopting the method, under the cheap metal salt catalyst, a plurality of ortho-substituted brominated and chloro products can be obtained with moderate to excellent yield.
Modular Entry to Functionalized Tetrahydrobenzo[ b]azepines via the Palladium/Norbornene Cooperative Catalysis Enabled by a C7-Modified Norbornene
Dong, Guangbin,Liu, Xin,Wang, Jianchun
supporting information, p. 9991 - 10004 (2021/07/19)
Tetrahydrobenzo[b]azepines (THBAs) are commonly found in many bioactive compounds; however, the modular preparation of functionalized THBAs remains challenging to date. Here, we report a straightforward method to synthesize THBAs directly from simple aryl iodides via palladium/norbornene (Pd/NBE) cooperative catalysis. Capitalizing on an olefin-tethered electrophilic amine reagent, an ortho amination followed by 7-exo-trig Heck cyclization furnishes the seven-membered heterocycle. To overcome the difficulty with ortho-unsubstituted aryl iodide substrates, we discovered a unique C7-bromo-substituted NBE (N1) to offer the desired reactivity and selectivity. In addition to THBAs, synthesis of other benzo-seven-membered ring compounds can also be promoted by N1. Combined experimental and computational studies show that the C7-bromo group in N1 plays an important and versatile role in this catalysis, including promoting β-carbon elimination, suppressing benzocyclobutene formation, and stabilizing reaction intermediates. The mechanistic insights gained could guide future catalyst design. The synthetic utility has been demonstrated in a streamlined synthesis of tolvaptan and forming diverse pharmaceutically relevant THBA derivatives. Finally, a complementary and general catalytic condition to access C6-substituted THBAs from ortho-substituted aryl iodides has also been developed.
Preparation method of 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzo[b]azepine
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, (2016/10/10)
The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of a key intermediate, namely, 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzo[b]azepine, of Tolvaptan. The synthetic method comprises four steps of A, the synthesis of 5-chloro-2-(di-allyl amino)-benzaldehyde, B, the synthesis of 1-allyl-7-chloro-2,3,4,5-tetrahydro-1H-2,5-epoxy benzo[b]azepine, C, the synthesis of 1-allyl-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzo[b]azepine, and D, the synthesis of 7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzo[b]azepine. According to the process route, the key intermediate of Tolvaptan is synthesized through four reactions of substitution, cyclization, ring-opening and deprotection, the synthetic steps are less, the operation is easy and convenient, the equipment requirement is low, the yield in each step is relatively high, column chromatography separation is not needed in the four reactions, and the synthetic method has the advantages that the technology is simple, the industrial scale production is facilitated, and the cost is low.
A the request cuts down the Pu Tanzania intermediate and its preparation method
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Paragraph 0065; 0066, (2019/02/02)
The invention discloses a 7-chloro-5-oxo-2, 3, 4, 5-tetrahydro-1H-1-benzoazepine carboxylic ester compound, its preparation method, and a method of utilizing the compound to prepare another tolvaptan intermediate 7-chloro-5-oxo-2, 3, 4, 5-tetrahydro-1H-1-benzoazepine. The 7-chloro-5-oxo-2, 3, 4, 5-tetrahydro-1H-1-benzoazepine prepared by the method provided in the invention has a high yield, and can be prepared by a one-pot process, thus greatly simplifying the reaction operation. Also, the used materials and reagents are cheap and commercially available, the reaction is mild and environment-friendly, so that the method is suitable for large-scale production.
A Cascade of acid-promoted c-o bond cleavage and redox reactions: From oxa-bridged benzazepines to benzazepinones
Zhang, Yuewei,Yang, Fengzhi,Zheng, Lianyou,Dang, Qun,Bai, Xu
, p. 6041 - 6043 (2015/01/09)
A sequence of C-O bond cleavage and redox reactions in oxa-bridged azepines was realized under acid promoted conditions. This protocol provides an atom-economical and straightforward approach to access benzo[b]azepin-5(2H)-ones in high yields. The formal synthesis of tolvaptan was achieved by exploiting this new transformation.
PROCESS FOR PREPARING TOLVAPTAN INTERMEDIATES
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Paragraph 0056; 0057, (2013/07/31)
The present invention provides a novel process for the preparation of 7-chloro-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one. The present invention also provides an improved process for the preparation of 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine. The present invention further provides an improved process for the preparation of 7-chloro-1-[2-methyl-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine.
PROCESS FOR PREPARING TOLVAPTAN INTERMEDIATES
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Page/Page column 8, (2012/04/23)
The present invention provides a novel process for the preparation of 7-chloro-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one. The present invention also provides an improved process for the preparation of 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine. The present invention further provides an improved process for the preparation of 7-chloro-1-[2-methyl-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine.
Efficient and promising asymmetric preparation of enantiopure tolvaptan via transfer hydrogenation with robust catalysts
Yin, Lu,Zheng, Yourou,Jia, Xian,Li, Xingshu,Chan, Albert S.C.
scheme or table, p. 2390 - 2393 (2010/12/25)
Enantiopure tolvaptan, the first and only oral vasopressin antagonist for hyponatremia has been prepared by using an asymmetric transfer hydrogenation as a key step with HCOOH-Et3N or HCOONa-H2O as the hydrogen donor in open air. Good chemical yields with up to 99% enantioselectivity were obtained with a 1000:1 of S/C in an HCOONa-H2O system. The air and water stable catalysts provide a very promising prospect for industrial application.
PROCESS FOR PREPARING BENZAZEPINE COMPOUNDS OR SALTS THEREOF
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Page/Page column 28, (2008/06/13)
This invention provides a process for preparing benzazepine compounds of the formula (1): wherein X1is a halogen atom, R1and R2are a lower alkyl group, or salts thereof as well as intermediate benzoic acid compounds in high yield and high purity on industrial scale, which are useful as an intermediate for preparing a pharmaceutically active 2,3,4,5-tetrahydro-1H-1-benzazepine compound having vasopressin antagonistic activity.
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
Kondo, Kazumi,Ogawa, Hidenori,Yamashita, Hiroshi,Miyamoto, Hisashi,Tanaka, Michinori,Nakaya, Kenji,Kitano, Kazuyoshi,Yamamura, Yoshitaka,Nakamura, Shigeki,Onogawa, Toshiyuki,Mori, Toyoki,Tominaga, Michiaki
, p. 1743 - 1754 (2007/10/03)
We previously reported a series of benzazepine derivatives as orally active nonpeptide arginine vasopressin (AVP) V2 receptor antagonists. After the lead structure OPC-31260 was structurally evaluated and optimized, the introduction of the 7-Cl moiety on the benzazepine and 2-CH3 on the aminobenzoyl moiety enhanced its oral activity. The new AVP-V2 selective antagonist OPC-41061 was determined to be a potent and orally active agent. Copyright (C) 1999 Elsevier Science Ltd.
