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Details for Patent: 8,273,735

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Details for Patent: 8,273,735

Title:Process for preparing benzazepine compounds or salts thereof
Abstract: This invention provides a process for preparing benzazepine compounds of the formula (1): wherein X.sup.1 is a halogen atom, R.sup.1 and R.sup.2 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. ##STR00001##
Inventor(s): Torisawa; Yasuhiro (Tokushima, JP), Abe; Kaoru (Tokushima, JP), Muguruma; Yasuaki (Tokushima, JP), Fujita; Shigekazu (Okazaki, JP), Ogawa; Hidenori (Tokushima, JP), Utsumi; Naoto (Tokushima, JP), Miyake; Masahiro (Tokushima, JP)
Assignee: Otsuka Pharmaceutical Co., Ltd. (Tokyo, JP)
Filing Date:Sep 01, 2006
Application Number:12/064,178
Claims:1. A process for producing a benzazepine compound of the formula (1): ##STR00028## wherein X.sup.1 is a halogen atom, R.sup.1 and R.sup.2 are independently a lower alkyl group, or salts thereof, which comprises reacting a benzazepine compound of the formula (2): ##STR00029## wherein X.sup.1 is as defined above, or a salt thereof with an amide compound of the formula (3): ##STR00030## wherein R.sup.1 and R.sup.2 are as defined above and X.sup.2 is a halogen atom, or a salt thereof in the presence of a carbonylating agent.

2. A process for producing a benzoic acid compound of the formula (4): ##STR00031## wherein R.sup.1 and R.sup.2 are independently a lower alkyl group, or a salt thereof, which comprises reacting an amide compound of the formula (11): ##STR00032## wherein R.sup.1 and R.sup.2 are as defined above, or a salt thereof, with a compound of the formula (19): X.sup.6COCOX.sup.7 (19) wherein X.sup.6 and X.sup.7 are independently a halogen atom.

3. A process for producing a benzoic acid compound of the formula (4): ##STR00033## wherein R.sup.1 and R.sup.2 are independently a lower alkyl group, or a salt thereof, which comprises oxidizing an amide compound of the formula (12): ##STR00034## wherein R.sup.1 and R.sup.2 are as defined above and X.sup.3 is a halogen atom, or a salt thereof.

4. A process for producing a benzoic acid compound of the formula (4): ##STR00035## wherein R.sup.1 and R.sup.2 are independently a lower alkyl group, or a salt thereof, which comprises hydrolyzing an amide compound of the formula (13): ##STR00036## wherein R.sup.1 and R.sup.2 are as defined above and X.sup.3 is a halogen atom, or a salt thereof.

5. A process for producing a benzoic acid compound of the formula (4): ##STR00037## wherein R.sup.1 and R.sup.2 are independently a lower alkyl group, or a salt thereof, which comprises oxidizing an amide compound of the formula (14): ##STR00038## wherein R.sup.1 and R.sup.2 are as defined above, or a salt thereof.

6. A process for producing a 2,3,4,5-tetrahydro-1H-1-benzazepine compound of the formula (10): ##STR00039## wherein X.sup.1 is a halogen atom, R.sup.1 and R.sup.2 are independently a lower alkyl group, or a salt thereof, which comprises reducing a benzazepine compound of the formula (1): ##STR00040## wherein R.sup.1, R.sup.2 and X.sup.1 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).

7. The process according to claim 6, wherein the hydrogenating agent is sodium borohydride which is used in an amount of 0.25 to 1 mole per 1 mole of the compound (1).

8. The process according to claim 7, wherein the hydrogenating agent is used in an amount of 0.25 to 0.5 mole per 1 mole of the compound (1).

9. The process according to claim 1, wherein the benzazepine compound (1) is 7-chloro-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahyd- ro-1H-1-benzazepin-5-one, or a salt thereof.

10. The process according to any one of claims 6, 7 and 8, wherein the 2,3,4,5-tetrahydro-1H-1-benzazepine compound (10) is 7-chloro-5-hydroxy-1-[2-methyl-4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-t- etrahydro-1H-1-benzazepine, or a salt thereof.

11. A benzazepine compound selected from 7-chloro-5-hydroxy-1-{2-methyl-4-[N-(2-methylbenzoyl)-N-(2-methyl-4-(2-me- thylbenzoylamino)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)benzoy- lamino]-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.
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