137982-91-3

Usage

Uses

Used in Pharmaceutical Industry:
7-Chloro-1,2,3,4-tetrahydro-1-(2-methyl-4-nitrobenzoyl)-5H-1-benzazepin-5-one is used as an intermediate in the synthesis of Tolvaptan-d7 (T536652), a labelled version of Tolvaptan (T536650). 7-Chloro-1,2,3,4-tetrahydro-1-(2-methyl-4-nitrobenzoyl)-5H-1-benzazepin-5-one serves as a selective, competitive arginine vasopressin V2 receptor antagonist, which is utilized in the treatment of hyponatremia (low blood sodium levels) associated with various medical conditions such as congestive heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone (SIADH). Its role in the synthesis process is crucial for the development of effective treatments for these conditions.

Upstream product

• 30459-70-2 2-methyl-4-nitrobenzoyl chloride 
• 160129-45-3 7-chloro-1,2,3,4-tetrahydro-5H-benzo[b]azepin-5-one 
• 201230-82-2 carbon monoxide 
• 7149-70-4 2-bromo-5-nitrotoluene 
• 106-47-8 4-chloro-aniline 
• 193686-76-9 7-chloro-1-(4-methylbenzenesulfonyl)-2,3,4,5-tetrahydro-1H-1-benzazepin-5-one 
• 247237-38-3 N-p-toluenesulfonyl-5-chloro-anthranilic acid methyl ester 
• 51282-49-6 methyl 5-chloro-2-nitrobenzoate 
• 1975-51-5 2-methyl-4-nitrobenzoic acid 
• 2516-95-2 5-chloro-2-nitrobenzoic acid 
• 5202-89-1 4-chlorobenzenesulfonyl chloride 
• 247237-43-0 methyl 5-chloro-2-[N-(3-ethoxycarbonyl)propyl-N-p-toluenesulfonyl]aminobenzoate 

Downstream Products

• 137977-97-0 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine 
• 150683-30-0 tolvaptan 
• 137973-76-3 MOP-21826 
• 331947-66-1 (+)-Tolvaptan 

Relevant academic research and scientific papers

IMPROVED METHODS OF PRODUCING SYNTHETIC INTERMEDIATES OF TOLVAPTAN

PROBLEM TO BE SOLVED: To provide improved methods of producing 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine. SOLUTION: The present invention provides methods of producing 7-chloro-1-[2-methyl-4-[(2-methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine and 7-chloro-1-(2-methyl-4-nitrobenzoyl)-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine, which are synthetic intermediates of tolvaptan, by condensing an amino group and a carboxyl group in the presence of magnesium hydroxide. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT

Preparation method of tolvaptan

The invention discloses a preparation method of tolvaptan. According to the preparation method, 7-chloro-1,2,3,4-tetrahydrobenzo[b]azepine-5-one and 4-nitro-2-methyl bromobenzene are taken as the primary raw materials; high purity tolvaptan is obtained after steps of carbonyl inserting reactions, reduction reactions, and acylation reactions, and the yield is high. The preparation method has the advantages that no bromine or tin dichloride is used; the preparation method does not generate a large amount of industrial waste water, and the environment is protected. At the same time, the generation of impurities namely a compound V and a compound VIII is avoided, and the purification becomes easier. No explosive, flammable, and toxic solvent such as chloroform, ether, and the like, is used, the requirements on the protection of workers are lowered, and the safe production is guaranteed. Moreover, the route design is novel, the raw materials are easily available, the operation of the technology is simple and feasible, and a simple and feasible method is provided for the massive industrial production of tolvaptan.

A method of preparing intermediates the request cuts down the Pu Tanzania

The invention relates to a method for preparing a tolvaptan intermediate, namely 7-chlorine-5-oxo-1-(2-methyl-4-nitrobenzene formyl)-1,2,3,4-tetrahydro-benzo-azepine. The tolvaptan intermediate which is a compound as shown in the formula (1) is obtained by 7-chlorine-5-oxo-2,3,4,5-tetrahydro-1H-1-benzo-azepine (2) reacting with 4-nitryl-2-methylbenzene formyl chloride (3). The tolvaptan intermediate prepared by the method has the advantages of high purity, high yield and short reaction time, thereby being suitable for large-scale industrialized production.

Preparation method of high-efficiency low-toxicity pitressin antagonist

The invention provides a preparation method of a high-efficiency low-toxicity pitressin antagonist. Specifically, the invention provides a compound having the formula A shown in the description, and a method for preparing tolvaptan through the compound having the formula A. All groups in the formula are defined in the description. The method has advantages of environmental protection, available raw materials, and high overall yield, and is suitable for industrial preparation of tolvaptan.

Preparation method for cardiovascular disease treatment drug

The invention provides a preparation method for a cardiovascular disease treatment drug. Specifically, the invention provides a compound represented by a formula (IV) shown in the description and a method for preparing Tolvaptan from the compound represented by the formula (IV). The method provided by the invention has the advantages of being environment-friendly, being easy in raw material obtaining and high in total yield, and the like, thereby being applicable to the industrialized preparation of Tolvaptan.

PROCESS FOR PREPARING TOLVAPTAN INTERMEDIATES

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

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

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.

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

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.