Process for preparing benzazepine compounds or salts thereof
AssigneeOtsuka Pharmaceutical Co., Ltd.
InventorsYasuhiro Torisawa, Kaoru Abe, Yasuaki Muguruma, Shigekazu Fujita, Hidenori Ogawa, Naoto Utsumi, Masahiro Miyake
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Abstract
This invention provides a process for preparing benzazepine compounds of the formula (1): wherein X1 is a halogen atom, R1 and R2 are 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.
Claims11
A process for producing a benzazepine compound of the formula (1):
- wherein X1 is a halogen atom, R1 and R2 are independently a lower alkyl group, or salts thereof, which comprises reacting a benzazepine compound of the formula (2):
- wherein X1 is as defined above, or a salt thereof with an amide compound of the formula (3):
- wherein R1 and R2 are as defined above and X2 is a halogen atom, or a salt thereof in the presence of a carbonylating agent.
A process for producing a benzoic acid compound of the formula (4):
- wherein R1 and R2 are independently a lower alkyl group, or a salt thereof, which comprises reacting an amide compound of the formula (11):
- wherein R1 and R2 are as defined above, or a salt thereof, with a compound of the formula (19):
- X6COCOX7 (19)
- wherein X6 and X7 are independently a halogen atom.
A process for producing a benzoic acid compound of the formula (4):
- wherein R1 and R2 are independently a lower alkyl group, or a salt thereof, which comprises oxidizing an amide compound of the formula (12):
- wherein R1 and R2 are as defined above and X3 is a halogen atom, or a salt thereof.
A process for producing a benzoic acid compound of the formula (4):
- wherein R1 and R2 are independently a lower alkyl group, or a salt thereof, which comprises hydrolyzing an amide compound of the formula (13):
- wherein R1 and R2 are as defined above and X3 is a halogen atom, or a salt thereof.
A process for producing a benzoic acid compound of the formula (4):
- wherein R1 and R2 are independently a lower alkyl group, or a salt thereof, which comprises oxidizing an amide compound of the formula (14):
- wherein R1 and R2 are as defined above, or a salt thereof.
A process for producing a 2,3,4,5-tetrahydro-1H-1-benzazepine compound of the formula (10):
- wherein X1 is a halogen atom, R1 and R2 are independently a lower alkyl group, or a salt thereof, which comprises reducing a benzazepine compound of the formula (1):
- wherein R1, R2 and X1 are as defined above, or a salt thereof in the presence of a hydrogenating agent selected from the group consisting of lithium aluminum hydride, sodium borohydride, zinc borohydride, and diborane in an amount of 0.25 to 1 mole per 1 mole of the compound (1).
A benzazepine compound selected from 7-chloro-5-hydroxy-1-{2-methyl-4-[N-(2-methylbenzoyl)-N-(2-methyl-4-(2-methylbenzoylamino)benzoylamino]benzoyl}-2,3,4,5-tetrahydro-1H-1-benzazepine (Compound A) or a salt thereof, 7-chloro-5-hydroxy-1-{2-methyl-4-[2-methyl-4-(2-methylbenzoylamino)benzoylamino]-benzoyl}-2,3,4,5-tetrahydro-1H-1-benzazepine (Compound B) or a salt thereof, 7-chloro-5-[2-methyl-4-(2-methylbenzoylamino)benzoyloxy]-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3-dihydro-1H-1-benzazepine (Compound C) or a salt thereof, or 7-chloro-5-[2-methyl-4-(2-methylbenzoylamino)benzoyloxy]-1-[2-methyl-4-(2-methylbenzoyl-amino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine (Compound D) or a salt thereof.
Dependencies are inferred from the claim text.