137977-97-0Relevant articles and documents
IMPROVED METHODS OF PRODUCING SYNTHETIC INTERMEDIATES OF TOLVAPTAN
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, (2018/04/07)
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
METHOD FOR PURIFYING 1-(4-AMINO-2-METHYLBENZOYL)-7-CHLORO-5-OXO-2,3,4,5-TETRAHYDRO-1H-1-BENZAZEPINE
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Paragraph 0020, (2018/04/06)
PROBLEM TO BE SOLVED: To provide a method for purifying 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine, which is one of the producing intermediates of tolvaptan. SOLUTION: This invention relates to a purification method, comprising the steps of: (a) making a rough 1-(4-amino-2-methylbenzoyl)-7-chloro-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine react with sulfonic acid, to conduct isolation as a sulfonate; (b) recrystallizing the sulfonate obtained at the step (a) from an organic solvent; and (c) making the sulfonate obtained at the step (b) react with a base to conduct desalination, thereby conducting isolation as a free object. SELECTED DRAWING: None COPYRIGHT: (C)2018,JPOandINPIT
Preparation method of tolvaptan
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, (2017/07/22)
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.