JPH02256671A - Benzoxazepine derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula I [A and B are both carbonyl or one of A and B is methylene and the other is carbonyl; R is (substituted) aromatic residue or (substituted) hetero group; X is H, halogen, 1-5C alkyl, 1-5C alkoxy, 7-9C arylalkoxy, OH, NO2 or ester group; n is 2-20] and a salt thereof. EXAMPLE:4-(3-(2-Pyridyl)piperazinyl)propyl)-2,3,4,5-tetrahydro-1,4-ben zoxazepin-5- one. USE:A psychopharmaceutical. Useful for treating diseases taking part in psychoneurosis such as anxiety neurosis, phobia, obsessional neurosis, intake disorder, climacteric disorder, serotonin nervous system such as infant autism. PREPARATION:A compound shown by formula II is reacted with a dihalogenated alkyl shown by formula III (Y is halogen) and a prepared new intermediate shown by formula IV is reacted with a compound shown by formula V to give a compound shown by formula I.

Description

Detailed Description of the Invention [Industrial Field of Application] The present invention relates to the general formula (1) (wherein A and B are both carbonyl groups, or one is a methylene group and the other is a carbonyl group, R represents an optionally substituted aromatic group or heterocyclic group, X is a hydrogen atom, a halogen atom (preferably chlorine, bromine, fluorine),
C, -C6 lower alkyl group (preferably C8 to C8 lower alkyl group), C1 to C6 lower alkoxy group (preferably C3 to C1 lower alkoxy group), C1 to C, arylalkoxy group (preferably phenylalkoxy group), benzoxane represented by a hydroxyl group, a nitro group, or an ester group (preferably a C1-C lower alkyl ester group, where n is an integer of 2 to 10, preferably 2 to 8, more preferably 2 to 5) The present invention relates to zepine derivatives, salts thereof, and psychotropic agents containing them as active ingredients.

The present invention further relates to the general formula (n) (wherein A and B are both carbonyl groups, or one is a methylene group and the other is a carbonyl group, and X is a hydrogen atom, a halogen atom (preferably chlorine, bromine, fluorine), C
, -C, lower alkyl group (preferably C, -C3 lower alkyl group), C+ -Cs lower alkoxy group (preferably c, -Cs lower alkoxy group), C1 to C9 arylalkoxy group (preferably phenylalkoxy group) ,
Hydroxyl group, nitro group or ester group (preferably C5-C
3 lower alkyl ester group), Y represents a halogen atom, and n is an integer of 2 to 10, preferably 2 to 8, more preferably 2 to 5), and salts thereof Regarding. This compound is useful as an intermediate for the synthesis of compounds of general formula (I).

The novel benzoxazepine derivatives represented by the general formula (1) of the present invention and their salts have a strong affinity for serotonin receptors and anti-conflict effects, and are effective in treating anxiety, phobias, etc. It is useful as a therapeutic agent for neuropsychiatric disorders such as obsessive-compulsive disorder, post-traumatic stress disorder, depressive neurosis, and psychosomatic disorders, as well as diseases involving the serotonin nervous system such as eating disorders, menopausal disorders, and childhood autism. .

[Conventional technology]

Conventionally, benzodiazepines, antipsychotics, antidepressants, etc. have been used as treatments for anxiety disorders, phobias, obsessive-compulsive disorders, etc., but there are problems with their effectiveness and side effects. It has become.

In particular, benzodiazepines have been mainly used to treat anxiety disorders, but they cause hypnosis, muscle relaxation, and even dependence, so the development of specific anti-anxiety drugs without these side effects. is desperately needed.

In recent years, various attempts have been made to solve these problems, and among them, drugs with selective affinity for the 5HT and A subtypes of serotonin receptors have the potential to become anxiolytic drugs with fewer side effects. It is believed that there is. In fact, drugs such as buspirone, diaviron, and ibusaviron have been developed or are being developed.

Buspirone [Problem to be Solved by the Invention] Although the above-mentioned buspirone, diepirone, ibusavirone, etc. partially alleviate various side effects compared to conventional benzodiazepine drugs, it is still far from sufficient (
There is a strong desire to develop anti-anxiety drugs with fewer side effects and higher specificity.

In order to develop an excellent anxiolytic drug that does not have the above-mentioned drawbacks, the present inventors need to use a more selective and more potent 5HT+
We believe that it is essential to create a drug that has affinity for the a receptor, and as a result of intensive research, we have found that the compound of the present invention, a novel benzoxazepine derivative, is an extremely potent 5HT IA.
The present invention was completed based on the discovery that it has not only receptor affinity but also an anxiolytic effect based on anti-conflict effect.

[Means to solve the problem]

The present invention provides benzoxazepine derivatives represented by general formula (I), pharmacologically acceptable acid addition salts thereof, and psychotropic agents containing these compounds as active ingredients.

The present invention provides benzoxazepine derivatives represented by general formula (II).

[Specific explanation]

The compound of general formula (I) according to the invention can be produced, for example, as follows.

Person■ Rim■ Person (n) Known Compound (I) More specifically, in the compound represented by the above general formula (1), a compound represented by the following general formula (Ia) in which A is a carbonyl group and B is a methylene group. The compounds mentioned are: G, S, 5idhu+G, Thyagarajan and Kuchi, T, Bhalerao, J.

Chem, Soc, (C), 969 (1966
Compound (III) with the following structure obtained according to the method described in 1.) or a similar method thereof is reacted with, for example, dibromoalkane to obtain compound (IV) with the following structure, and then condensed with a piperazine derivative by a conventional method. It can be synthesized by

Furthermore, in the compound represented by the general formula (1),
The following formula (I) in which A is a methylene group and B is a carbonyl group
Compound (I b) represented by b) is a compound of Kost, A.
N., 5tankevicius, A.; Khim
, Geterotsikt.

5 oed ire, ? (9), 1288
(1971) and similar methods thereto is reacted with dibromoalkane to obtain compound (VT) with the following structure, which is then condensed with a piperazine derivative. It can be synthesized by

Furthermore, in the compound represented by the general formula (1),
The compound represented by the general formula (I c) in which both A and B are carbonyl groups is 8. Cattaneo.

P, Ga1in+berti, M, MelandrtB
Boll, Chim, Farm, +102541 (
It can be synthesized by reacting the compound (■) obtained according to the method described in (1963) and similar methods thereof with dibromobutane to obtain the compound (■) having the following structure, and then condensing it with a piperazine derivative. can.

In the penzoxebine derivative of general formula (I) according to the present invention, R represents an optionally substituted aromatic group and a heterocyclic group, as described above.

Examples of such aromatic groups include 06 to CI+1 aromatic groups, specifically phenyl groups, naphthyl groups, etc.
These aromatic groups include, for example, halogen atoms (chlorine 4, bromine, fluorine, etc.), hydroxyl groups, 01-C4 lower alkyl groups,
C6-C1 lower alkoxy group, arylalkoxy group,
It may be substituted with a nitro group, an amino group, an amide group, a cyano group, an ester group (for example, a C00/C1-C1 lower alkyl group), or the like.

On the other hand, the heterocyclic group is preferably 1 to 3 in the 5 to 7R ring.
Rings containing nitrogen atoms, specifically, pyridine groups, pyrimidinyl groups, pyrazinyl groups, pyridazinyl groups, imidazolyl groups, etc., and these heterocyclic groups may be substituted with the above-mentioned substituents.

Novel benzoxazepine derivatives represented by the general formula (I) of the present invention and pharmacologically acceptable salts thereof (e.g. hydrochloride, nitrate, sulfate, hydrobromide, phosphate,
methanesulfonate, acetate, oxalate, succinate, malonate, tartrate, maleate, fumarate,
Lactate, citrate, etc.) may be administered alone, but may be mixed with other conventional pharmacologically acceptable carriers, excipients, diluents, etc. as necessary or desired. Dosage form (
For example, tablets, capsules, powders, liquids, injections, halved)
It can be administered orally or parenterally. Examples of such diluents or carriers include, for example, polyvinylpyrrolidone, gum arabic, gelatin, sorbitol, cyclodextrin, tragacanth, magnesium stearate, talc, polyethylene glycol, polyvinyl alcohol, silica, milk-tL crystalline cellulose,
Sugar, starch, calcium phosphate, vegetable oil, calcium carboxymethylcellulose, sodium lauryl sulfate,
Examples include water, ethanol, glycerin, mannitol, and syrup.

There are no particular limitations on the concentration of the compound of formula (1) in such pharmaceutical preparations, but it is generally appropriate to range from about 1 to 100% by weight, preferably from about 10 to 100% by weight. Also, there is no particular limitation on the dose, but it is 0.1 to 1000 ■/day/
The dose per person, preferably 1 to 500 mg/day/person, is appropriate, and the administration frequency is usually 1 to 4 times per day.

〔Example〕

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples and Test Examples, but it goes without saying that the scope of the present invention is not limited to these Examples.

First, the method for synthesizing intermediate compound (n) will be explained in Examples 1 to 18, and the method for synthesizing final compound N) will be explained in Examples 19 to 95.

Synthesis of 4-(3-chloropropyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one on a plate 2.3,4,5-tetrahydro-1,4-benzo 1 g of oxazepin-5-one was added to 50 ml of dioxane, 12 ml of dimethyl sulfoxide, and 1 ml of dimethyl sulfoxide. 60% sodium hydride was added thereto, and the mixture was heated and stirred at 110° C. for 1 hour.

After cooling with water, 1.82 ml (3 equivalents) of 1-
Bromo-3-chloropropane was added and stirred at room temperature for 17 hours. Dioxane was distilled off from the resulting reaction solution, ice water was added, and the mixture was extracted with ether.

This ether extract was washed three times with brine and dried over anhydrous magnesium sulfate. Next, this ether solution was concentrated, and the residue was subjected to silica gel column chromatography and developed with hexane-ethyl acetate (6:4) to obtain 1.21 g (yield: 83%) of the title compound.

■1 Synthesis of 4-(3-bromopropyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine 3,5-dione 2.3,4,5-tetrahydro-1,4-benzo 100 μm of oxazepine-3,5-dione was dissolved in 10 μm of dimethylformamide, and after cooling on ice, 0.172 d (1/3
．． 3-Sifronpropane, 27.1■ (1.2 equivalents)
60% sodium hydride was added thereto, and the mixture was stirred for 1 hour under water cooling.

The resulting reaction solution was poured into an aqueous citric acid solution while cooling with water, and extracted with ether. After washing with brine, it was dried over anhydrous magnesium sulfate. The ether solution was concentrated, and the residue was subjected to silica gel column chromatography and developed with hexane-ethyl acetate (8:2) to obtain the title compound (79.8m).
g (yield 47%) was obtained.

Kairi 4-(3-bromopropyl)-7-medoxy 2.3,
4.5-tetrahydro-1,4-benzoxazepine-
Synthesis of 3,5-dione 7-medoxy 2,3.4.5-tetrahydro-1,4
-Dissolve 828 μm of benzoxazepine-3,5-dione in 20 volumes of dimethylformamide, add 1.62 g (2 equivalents) of 1,3-dibromopropane, and after cooling with water,
0.1 (1.5 equivalents) of 60% sodium hydride was added and stirred for 1 hour under water cooling.

Reaction treatment and purification were carried out in the same manner as in Example 2 to obtain 2801 g of the title compound.
(yield 21.3%).

Flood 4-(3-bromopropyl)-8-methyl-2°3.4
．． 5-tetrahydro-1,4-benzoxazepine-3
, 5-Dione 8-Methyl-2,3,4,5-tetrahydro 1.4-Benzoxazepine-3,5-dione 764 μm was dissolved in dimethylformamide 20-1.62 g (2 equivalents) ) of 1,3-dibromopropane was added, and after cooling with water, 240 mg
(1,5 equivalent ff1) of 60% sodium hydride was added and stirred at room temperature for 30 minutes.

Reaction treatment and purification were carried out in the same manner as in Example 2 to obtain 417 mg of the title compound.
(yield 33.4%).

Synthesis of n-de-4-(4-brombutyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one 2.3,4,5-tetrahydro-1,4-benzoxase 2 g of pin-5-one was dissolved in 100 d of dioxane and 10 d of dimethyl sulfoxide, and 736 μ (1.5 equivalents)
60% sodium hydride was added thereto, and the mixture was heated and stirred at 110°C for 30 minutes. After cooling with water, add 4.49 m1C to this reaction solution.
Add 2 equivalents of 1,4-sifurombutane at room temperature.
Stir for hours.

Reaction treatment and purification were carried out in the same manner as in Example 1 to obtain 2.56 g of the title compound.
(yield 70%).

[1 Synthesis of 4-(4-brombutyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-3-one 2.3.4.5-Tetrahydro-1,4-benzoxa Zepin-3-one 5C)O was dissolved in 50d of dioxane and 5d of dimethylsulfoxy, 184 mg (1.5 equivalents) of 60% sodium hydride was added, and the mixture was heated and stirred at room temperature for 30 minutes. Add 1.12d (3 equivalents) of 1,4 to this reaction solution.
-Dibromobutane and 5 volumes of dimethylformamide were added and stirred at room temperature for 3 hours.

Ice water was added to the resulting reaction solution and extracted with ether. The extract was washed with brine and dried over anhydrous magnesium sulfate. After concentrating the ether solution, the residue was purified using silica gel column chromatography using hexane-ethyl acetate (7:
3) to obtain 504 mg of the title compound (yield 55%)
I got it.

Synthesis of 4-(4-brombutyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3°5-dione 2.3,4.5-tetrahydro-1,4- 10 g of benzoxazepine-3,5-dione was dissolved in 100 g of dimethylformamide, and after cooling with water, 20.7 d (1.
4-dibromobutane, 2.71 g (1,2 eq.) of 60
% sodium hydride was added, and the mixture was stirred for 1.5 hours under ice cooling.

After reaction treatment and purification in the same manner as in Example 2, the title compound 10.
3g (yield 58%) was obtained.

Kanku 4-(4-brombutyl)-7-medoxy 2°3.4
．． 5-tetrahydro-1,4-benzoxazepine-3
, 5-dione synthesis 7-medoxy 2,3,4.5-tetrahydro-1,4
-Dissolve 414 ■ of benzoxazepine-3,5-dione in 10 d of dimethylformamide, and after cooling with water, 120 ■
Add (1,5 equivalents) of 60% sodium hydride to 10
After stirring for a minute, 860 μ (2 equivalents) of 1°4-dibromobutane was added and stirred at room temperature for 1 hour.

Reaction treatment and purification were carried out in the same manner as in Example 2 to obtain 345 mg of the title compound.
(yield 50.4%).

8-chloro-4-(4-brombutyl)-2°3.4.
5-tetrahydro-1,4-benzoxazepine-3,
Synthesis of 5-dione 8-chloro-2,3,4,5-tetrahydro-1,4-
1.5 g of benzoxazepine-3,5-dione was dissolved in 40 ml of dimethylformamide, and after cooling with water, 1.30 g (1.5 equivalents) of 1,4-dibromobutane, 340 g (
1.2 equivalents) of 60% sodium hydride was added, and the mixture was stirred for 30 minutes under water cooling.

After reaction treatment and purification in the same manner as in Example 2, the title compound 920
(yield 37%).

Packing 4-(4-brombutyl)-8-methyl-2゜3.4.
5-tetrahydro-1,4-benzoxazepine-3,
Synthesis of 5-dione 8-methyl-2,3,4,5-tetrahydro-1,4-
764 ml of benzoxazepine-3,5-dione was dissolved in 20 ml of dimethylformamide, 1.72 g (2 equivalents) of 1,4-dibromobutane was added, and after cooling with water, 240 ml of benzoxazepine-3,5-dione was dissolved.
(1.5 eq.) of 60% sodium hydride was added and stirred at room temperature for 1.5 hours.

The same reaction treatment and purification as in Example 2 yielded the title compound 880■ (
A yield of 67.5% was obtained.

■Dan8-methoxy-4-(4-brombutyl)-2°3.4
．． 5-tetrahydro-1,4-benzoxazepine-3
,5-dione synthesis 8-methoxy-2,3,4,5-tetrahydro-1,4
- 1 g of benzoxazepine-3,5-dione was dissolved in dimethylformamide 30, and after cooling with water, 1.77 d (3
232 mg (equivalent)
1.2 equivalents) of 60% sodium hydride was added, and the mixture was stirred for 1.5 hours under water cooling.

Reaction treatment and purification were carried out in the same manner as in Example 2 to obtain 1.25 g of the title compound.
(yield 76%).

Pan■ 6-medoxy 4-(4-brombutyl)-23,4,
5-tetrahydro-1,4-benzoxazepine-3,
Synthesis of 5-dione 6-medoxy 2,3,4.5-tetrahydro-1,4
-Dissolve 204 μ of benzoxazepine-3,5-dione in 20 d of dimethylformamide, and after cooling with water, 0.361
m (1,4-dibromobutane per 3,47.4■(
1.2 equivalents) of 60% sodium hydride was added, and the mixture was stirred for 1.5 hours under water cooling.

The reaction treatment and purification were carried out in the same manner as in Example 2 to obtain the title compound 117■
(yield 35%).

Charcoal ■ 6-benzyloxy-4-(4-bromobutyl) 2.3
, 4.5-tetrahydro-1,4-benzoxazepine-3,5-dione, synthesis of 6-benzyloxy-2,3
, 4,5-tetrahydro-1,4-benzoxazepine-3,5-dione 410 μm in dimethylformamide 40 μm
After cooling with water, 0.265 m (1,5 equivalent N) of 1,4-dibromobutane and 69.5 m (1,2 equivalent) of 60% sodium hydride were added, and the mixture was stirred for 1 hour under water cooling. .

Reaction treatment and purification were carried out in the same manner as in Example 2 to obtain 450 mg of the title compound.
(yield 74%).

Packing 7-nitro-4-(4-brombutyl)-2°3.4.
5-tetrahydro-1,4-benzoxazepine-3,
Synthesis of 5-dione 7-nitro-2,3,4,5-tetrahydro-1,4-
56.3 μm of benzoxazepine-3,5-dione was dissolved in dimethylformamide 10, and after cooling on ice, the solution was 0.092 μl.
7d (3 equivalents) of 1,4-dibromobutane, 12.2
(1.2 equivalents) of 60% sodium hydride was added, and the mixture was stirred for 2 hours under water cooling.

The title compound 16.4■ was obtained by reaction treatment and purification in the same manner as in Example 2.
(yield: 18%).

! ■ 7-Medoxycarbonyl-4-(4-brombutyl)
-Synthesis of 2,3,4,5-tetrahydro-1,4benzoxazepine-3,5-dione 7-medoxycarbonyl-2.3.4.5-tetrahydro-1,4-benzoxazepine 125 mg of -3゜5-dione was dissolved in 10 ml of dimethylformamide, and after cooling with water, 0.193 d (
1,4-dibromobutane, 25.3■ (1,
2 equivalents) of 60% sodium hydride was added, and the mixture was stirred for 1 hour under water cooling.

The title compound 124■(
A yield of 63% was obtained.

Synthesis of Punishment 1-(5-bromopentyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione 2.3,4.5-tetrahydro-1,4- 300 μm of benzoxazepine-3,5-dione was dissolved in 3M dimethylformamide, and after cooling with water, 0.693 d (3 equivalents) of 1
, 5-Sifrompengkun, 81.4■ (1,2 equivalents)
60% sodium hydride was added thereto, and the mixture was stirred for 30 minutes under ice cooling.

After reaction treatment and purification in the same manner as in Example 2, the title compound 238
(yield 43%).

KanU 4-(5-brompentyl)-7-medoxy 2.3,
4.5-tetrahydro-1,4-benzoxazepine-
Synthesis of 3,5-dione 7-medoxy2,3,4.5-tetrahydro1,4-
Benzoxazepine-3,5-dione (621) was dissolved in 10-dimethylformamide, 1.38 g (2 equivalents) of 1,5-dibrompenkune was added, and after cooling with water, 180
(1) (1.5 equivalents) of 60% sodium hydride was added, and the mixture was stirred at room temperature for 4 hours.

The title compound 396 was obtained by reaction treatment and purification in the same manner as in Example 2.
(yield 37.1%) was obtained.

Packing 4-(5-bromopentyl)-8-methyl-2°3.4
．． 5-tetrahydro-1,4-benzoxazepine-3
Synthesis of ,5-dione 8-methyl-2,3,4,5-tetrahydro-1,4-
20m of benzoxazepine-3,5-dione 764■
1! of dimethylformamide to yield 2.07 g (2.
(equivalent) of 1,5-dibrombencune was added, and after cooling with water, 2
40 μ (1.5 equivalents) of 60% sodium hydride was added and stirred at room temperature for 30 minutes.

The reaction treatment and purification were carried out in the same manner as in Example 2 to obtain the title compound 680
A yield of 50.0%) was obtained.

Physical data of the compounds obtained in Examples 1 to 18 above are shown in Table 1.

■■ Synthesis of 4-(3-(4-(2-pyridyl)piperazinyl)propyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one 4-(3- (4-(3-chlorophenyl)piperazinyl)propyl) -2,3,4,5-tetrahydro-1
, 4-Benzoxazepin-5-one Compound 289 of Synthesis Example 1 was dissolved in dioxane 30-, and 0
．． 937m (5 equivalents) of 1-(2-pyridyl)piperazine was added and heated to reflux for 17 hours. Next, dioxane was distilled off, diluted sodium chloride solution was added, and the mixture was extracted with methylene chloride.

This extract was washed with saturated brine and then dried over anhydrous magnesium sulfate. Next, this methylene chloride solution was concentrated, and the residue was subjected to column chromatography on silica gel and developed with methylene chloride-methanol (97:3) to obtain the title compound 320.mu. (yield 73%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from ethanol-ether.

300 ml of the compound of Example 1 was dissolved in 30 d of dioxane, and 1
．． 23 g (5 equivalents) of 1-(3-chlorophenyl)piperazine was added and heated under reflux for 17 hours.

The title compound 380 was obtained by reaction treatment and purification in the same manner as in Example 19.
(2) (yield 76%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from ethanol-ether.

Compound of Synthesis Example 2 of Kago 4-(3-(4-(2-pyridyl)piperazinyl)propyl)-2,3,4,5-tetrahydro-1,4-benzogisazepine-3,5-dione Dissolve 50■ in dioxane 10I11,
0.133(5 equivalents) of 1-(2-pyridyl)piperazine was added and stirred at 100°C for 17 hours.

The reaction was carried out in the same manner as in Example 19, and ethyl acetate-hexane (3:1) was added using silica gel column chromatography.
The reaction mixture was developed to obtain 48.0 ml of the title compound (yield 75%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Punishment 4- (3-(4-(2-pyrimidinyl)piperazinyl)propyl)-2,3,4,5-tetrahydro-1,4
-Compound 60 of Synthesis Example 2 of benzoxazepine-3,5-dione was dissolved in dioxane 10Id, and 1
68 μm (5 equivalents) of 1-(2-pyrimidinyl)piperazine was added and stirred at 100°C for 17 hours.

Work-up was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21 to obtain 61.6 mm of the title compound (yield: 80%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

■ Gate 7-Medoxy 4- (3-(2-pyridyl)piperazinyl)propyl) -2,3,4,5-tetrahydro-
Compound 98 of Synthesis Example 3 of 1,4-benzoxazepine-3,5-dione was dissolved in dioxane 1011r1, 147 mg (3 equivalents) of 1-(2-pyridyl)piperazine was added, and the mixture was heated at 100°C. Stirred for 20 hours.

The reaction solution was poured into ice water and extracted with ethyl acetate.

After drying the organic layer over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure. The residue was subjected to silica gel column chromatography and developed with ethyl acetate to obtain the title compound 88.
(yield 71.5%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

■Compound of Synthesis Example 3 of 7-medoxy4-(3-(2-pyrimidinyl)piperazinyl)propyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3°5-dione 98■ in dioxane 10M1,
47 μm (3 equivalents) of 1-(2-pyrimidinyl)piperazine was added and stirred at 100°C for 20 hours.

The title compound 107■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 86.8%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

8-Methyl-4-(3-(2-pyridyl)piperazinyl)propyl)-2,3,4,5-tetrahydro-1,
Compound 125 of Synthesis Example 4 of 4-benzoxazepine-3,5-dione was dissolved in 10 m of dioxane, and 1
96 g (3 equivalents) of 1-(2-pyridyl)piperazine was added and refluxed for 48 hours.

The title compound 113■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 71.7%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

8-Methyl-4-(3-(2-pyrimidinyl)piperazinyl)propyl) -2,3,4,5-tetrahydro-
Compound 125 of Synthesis Example 4 of 1,4-benzoxazepine-3°5-dione was dissolved in 10M1 of dioxane,
196 ml (3 equivalents) of 1-(2-pyrimidinyl)piperazine was added and stirred at 90-100''C for 48 hours.

The title compound 133 was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 84.1%) was obtained. The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Compound 300 of Synthesis Example 5 of 4-(4·-(4-(2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-5-one
was dissolved in dioxane 30d, 0.782r11 (5 equivalents) of 1-(2-pyridyl)piperazine was added, and the mixture was heated under reflux for 2 hours.

Work-up and purification in the same manner as in Example 19 yielded 342 mg of the title compound.
(yield 89.4%).

Kago 4- (4-(4-(2-pyrimidinyl)piperazinyl)butyl) -2,3,4,5-tetrahydro-1,4
-Compound 3 of Synthesis Example 5 of Benzoxazepine-5-one
Dissolve 00■ in 30- dioxane, 825a+g
(5 equivalents) of 1-(2-pyrimidinyl)piperazine was added and heated under reflux for 17 hours.

The title compound 275 was obtained by reaction treatment and purification in the same manner as in Example 19.
(2) (yield 72%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from ethanol-ether.

f! 1B 4- (4-(4-(3-chlorophenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro 1,4
-Dissolve 300 μ of the compound of Synthesis Example 5 of benzoxazepine-5-・one in 30 μm of dioxane, and
86 μm (5 equivalents) of 1-(3-chlorophenyl)piperazine was added, and the mixture was heated under reflux for 4 hours.

Reaction treatment and purification were carried out in the same manner as in Example 19 to obtain 399 g of the title compound.
(yield 96%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from ethanol-ether.

4-(4-(4-(2-methoxyphenyl)piperazinyl)butyl-2,3,4,5-tetrahydro-1,4
- 300 μm of the compound of Synthesis Example 5 of benzoxazepine-5-one was dissolved in 30 m of dioxane, and 0
．． 902d (5 equivalents) of 98% 1-(2-methoxyphenyl)piperazine was added and heated to reflux for 2 hours.

The reaction treatment and purification were carried out in the same manner as in Example 19, and the title compound 387m
g (yield 94%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from ethanol-ether.

Compound 100 of Synthesis Example 6 of 4-(4-(4-(2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepin-3-one
was dissolved in 10d of dioxane, 0.26m (5 equivalents)
1-(2-pyridyl)piperazine was added thereto, and the mixture was heated under reflux for 11 hours.

The title compound 125 was obtained by reaction treatment and purification in the same manner as in Example 19.
(2) (yield 98%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt by a conventional method and then recrystallizing it from methylene chloride-ether.

■I4- (4-(4-(2-pyrimidinyl)piperazinyl)butyl) -2,3,4,5-tetrahydro-1,4
-Compound 1 of Synthesis Example 6 of benzoxazepine-3-one
00■ was dissolved in 10d of dioxane, 275■ (5 equivalents) of 1-(2-pyrimidinyl)piperazine was added, and 1
The mixture was heated under reflux for 7 hours.

The title compound 118 was obtained by reaction treatment and purification in the same manner as in Example 19.
mg (yield 92%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Tetra 4-(4-(4-(3-chlorophenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4
-Dissolve 100 μ of the compound of Synthesis Example 6 of benzoxazepine-3,5-one in 10 rI of dioxane, and dissolve 330 μ (5 equivalents) of 1-(3-chlorophenyl).
Piperazine was added and the mixture was heated under reflux for 11 hours.

The title compound 137 was obtained by reaction treatment and purification in the same manner as in Example 19.
(2) (yield 99%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from ethanol-ether.

■Nail 4- (4-(4-phenylpiperazinyl)butyl)
Compound 156 of Synthesis Example 7 of -2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione
was dissolved in 10 M1 of dioxane, 243 μ (3 equivalents) of phenylpiperazine was added, and the mixture was stirred at 90-100° C. for 12 hours.

The title compound 180■ was obtained by reaction treatment and purification in the same manner as in Example 23
(yield 91.5%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ethyl acetate.

Punishment 4- (4-(4-(2-fluorophenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,
4-benzoxazepine-3,5-dione synthesis example 7 compound 100■ was dissolved in dioxane 10jd,
173 mg (3 equivalents) of 1-(2-fluorophenyl)
Piperazine was added and the mixture was heated under reflux for 5 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain the title compound 126 (yield: 96%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

fi 4- (4-(4-(2-chlorophenyl)piperazinyl)butyl) -2,3,4,5-tetrahydro-1,
Compound 100■ of Synthesis Example 7 of 4-benzoxazepine-3,5-dione was mixed with dioxane 10Ild! 315 μ (5 equivalents) of 1-(2-chlorophenyl) dissolved in
Piperazine was added and the mixture was heated under reflux for 17 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain the title compound 114 (yield: 83%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Punishment 4- (4-(4-(2-methoxyphenyl)piperazinyl)butyl) -2,3,4,5-tetrahydro-1
,, Compound 174 of Synthesis Example 7 of 4-benzoxazepine-1,3-dione was dissolved in dioxane 20, and
, 5 d of 1-(2-methoxyphenyl)piperazine was added, and the mixture was heated under reflux for 6 hours.

The product was worked up in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain the title compound 198 (yield: 84%). In addition, hydrochloride is
It was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Punishment 4- (4-(4-(2-hydroxyphenyl)piperazinyl)butyl) -2,3,4,5-tetrahydro-
1,4-Benzoxazepine-3,5-dione Synthesis Example 7 Compound 100 was dissolved in dioxane 20, and 1
71 cm (3 equivalents) of 1-(2-hydroxyphenyl)piperazine was added and the mixture was heated and stirred at 100°C for 17 hours.

The reaction treatment was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain the title compound 128 (yield: 98%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Cleavage 4-(4-(4-(3-chlorophenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4
- Compound 200atg of Synthesis Example 7 of benzoxazepine-3,5-dione was mixed with dioxane 20rIII/
, and 631 μ (5 equivalents) of 1-(3-chlorophenyl)piperazine was added thereto, followed by heating under reflux for 17 hours.

Reaction treatment was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21.
The title compound 266■ (yield 97%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Dish residue 4- (4-(4-(3-methoxyphenyl)piperazinyl)butyl) -2,3,4,5-tetrahydro-1
, 4-Benzoxazepine-3,5 dione Synthesis Example 7 Compound 68.4 was dissolved in dioxane 10111, and 131 (3 equivalents) of 1-(3-methoxyphenyl)piperazine was added thereto for 12 hours. The mixture was heated and stirred at 'C.

Reaction treatment was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21.
82.1■ (yield: 88%) of the title compound was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Box 4- (4-(4-(3-methylphenyl)piperazinyl)butyl') -2,3,4,5-tetrahydro-1
, 100 μ of the compound of Synthesis Example 7 of 4-benzoxazepine-3,5-dione was dissolved in 20 ae of dioxane,
169 μ (3 equivalents) of 1-(3-methylphenyl) and perazine were added, and the mixture was heated and stirred at 100°C for 10 hours.

Reaction treatment was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21.
The title compound 127■ (yield 97%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

■婬4-(4-(4-(3-trifluoromethylphenyl)
2,3,4゜5-tetrahydro-1,4-benzoxazepine-3,5-dione Compound 100 of Synthesis Example 7 was dissolved in dioxane 10d,
28 μ (3 equivalents) of 1-(3-)lifluoromethylphenyl)piperazine was added, and the mixture was heated and stirred at 100°C for 17 hours.

Reaction treatment was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21.
The title compound 136■ (yield 91%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

4-(4-(4-(4-fluorophenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,
100 μ of the compound of Synthesis Example 7 of 4-benzoxazepine-3,5-dione was dissolved in 10 d of dioxane, and 1
51 cm (3 equivalents) of 1-(4-fluorophenyl) and perazine were added, and the mixture was heated and stirred at 100°C for 17 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain the title compound 122 (yield: 99%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

4-(4-(4-(4-chlorophenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4
-Dissolve 100 μ of the compound of Synthesis Example 7 of benzoxazepine-3,5-dione in dioxane 10-
89+ag (3 equivalents) of 1-(4-chlorophenyl)
Piperazine was added and the mixture was heated under reflux for 15 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain the title compound 113 (yield: 83%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

■Dan4-(4-(4-(4-methoxyphenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1
, 4-Benzoxazepine-3,5-dione Compound 94.1 of Synthesis Example 7 was dissolved in dioxane 10d,
299 ml (5 parts) of 1-(4-methoxyphenyl)piperazine was added, and the mixture was heated under reflux for 6 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain 104 mg (yield: 81%) of the title compound. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

4-(4-(4-(4-acetylphenyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,
100 μ of the compound of Synthesis Example 7 of 4-benzoxazepine-3,5-dione was dissolved in 10-dioxane, and 2
16 ml (3 equivalents) of 94% 4-piperazinoacetophenone was added, and the mixture was heated and stirred at 100°C for 17 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain the title compound 101 (yield: 72%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

4-(4-(4-(2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione Compound 200 of Example 7
Dissolve ■ in 20d dioxane, 0.498m (5
equivalent) of 1-(2-pyridyl)piperazine was added, and 17
The mixture was heated to reflux for an hour.

Reaction treatment was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21.
The title compound 196■ (yield 78%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

4fi 4- (4-(4-(3-chloro-2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-
Compound 156 of Synthesis Example 7 of 1,4-benzoxazepine-3,5-dione was dissolved in dioxane 101d,
295 μ (3 equivalents) of 1-(3-chloro-2-pyridyl)piperazine was added and stirred at 100°C for 24 hours.

The title compound 225■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 98.0%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

■Synthesis of 4-(4-(4-(3-nitro-2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione Compound 156 of Example 7 was dissolved in dioxane 10d,
12+ng (3 equivalents) of 1-(3-nitro-2-pyridyl)piperazine was added and refluxed for 23 hours.

The title compound 210■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 95.5%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Open-cut 4- Synthesis example of (4-(4-(3-cyano-2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-sion Dissolve compound 156K of 7 in dioxane 10td,
282 μ (3 equivalents) of 1-(3-cyano-2-pyridyl)piperazine were added and the mixture was refluxed for 20 hours.

The title compound 190■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 90.6%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Example of synthesis of (4-(4-(3-amino-2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione 94 mg of compound No. 7 was dissolved in dioxane 6-,
0.1 (3 equivalents) of 1-(3-amino-2-pyridyl)piperazine was added and the mixture was refluxed for 48 hours.

The title compound 94■(
A yield of 76.5% was obtained. Note that the hydrochloride was converted into a hydrochloride by a conventional method, and then recrystallized from ethanol-ether.

Charcoal 4-(4-(4-(2-pyrimidinyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4
-Dissolve 500 μ of the compound of Synthesis Example 7 of benzoxazepine-3,5-dione in 50-dioxane,
1.31 g (5 equivalents N) of 1-(2-pyrimidinyl)piperazine was added, and the mixture was heated under reflux for 17 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 2] to obtain the title compound 602 (yield: 95%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

7-medoxy4- (4-(4-(2-pyridyl)piperazinyl)butyl)-2,3,4,5tetrahydro-
100 μ of the compound of Synthesis Example 8 of 1,4-benzoxazepine-3°5-dione was dissolved in 10 m of dioxane, and 1
47 μm (3 equivalents) of 1-(2-pyridyl)piperazine was added and stirred at 90°C for 48 hours.

The title compound 108■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield: 84.8%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

7-Medoxy 4- (4-(4-(3-chloro-2-
pyridyl)piperazinyl)butyl)-2゜3.4.5-
Tetrahydro-1,4-benzoxazepine-3,5-
Compound 137■ of Dione Synthesis Example 8 was dissolved in dioxane 10d, and 2
36■ (3 equivalents) of 1-(3-chloro-2-pyridyl)
Piperazine was added and the mixture was refluxed for 40 hours.

The title compound 209■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 99.1%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Basket 7-Medoxy 4- (4-(4-(3-nitro-2-
pyridyl)piperazinyl)butyl)-2゜3.4.5-
Tetrahydro-1,4-benzoxazepine-3,5-
Compound 137 of Dione Synthesis Example 8 was dissolved in dioxane 10-,
49■ (3 equivalents) of 1-(3-nitro-2-pyridyl)
Piperazine was added and the mixture was refluxed for 40 hours.

The title compound 182■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 96.9%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Opening 7-Medoxie 4- (4-(4-(3-cyano-2-
pyridyl)piperazinyl)butyl)-2゜3.4.5-
Tetrahydro-1,4-benzoxazepine-3,5-
Compound 138■ of Dione Synthesis Example 8 was dissolved in dioxane 10d, and 2
25■ (3 equivalents) of 1-(3-cyano-2-pyridyl)
Piperazine was added and the mixture was refluxed for 40 hours.

The title compound 182■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 98.5%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Punishment 7, -methoxy-4-(4-(4-(3-amino-2-
pyridyl)piperazinyl)butyl)-2゜3.4.5-
Tetrahydro-1,4-benzoxazepine-3,5-
Compound 244 of Dione Synthesis Example 55 was dissolved in 10 d of ethanol,
50 μ of platinum dioxide was added and hydrogenated for 0.5 hour.

The reaction solution was filtered, the filtrate was distilled off under reduced pressure, and the residue was subjected to column chromatography on silica gel, eluting with ethyl acetate to obtain the title compound 179 (yield: 83o4%). Note that the hydrochloride was converted into a hydrochloride by a conventional method, and then recrystallized from ethanol-ether.

7-Medoxy 4-(4-(4-(2-pyrimidinyl)
Piperazinyl)butyl)-2,3,4゜5-tetrahydro-1,4-benzoxazepine 3.5-dione Compound 100 of Synthesis Example 8 was dissolved in dioxane 10d, and 1
47 μ (3 equivalents) of 1-(2-pyrimidinyl)piperazine was added and stirred at 90°C for 48 hours.

The title compound 116■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 90.9%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Sh8-chloro-4-(4-(4-(2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-
Synthesis of 1,4-benzoxazepine-3,5-dione I Dissolve 98.0 ■ of the compound of Example 9 in 10 d of dioxane,
0.132 d (3 equivalents) of 1-(2-pyridyl)piperazine was added, and the mixture was heated and stirred at 100°C for 10 hours.

The reaction treatment was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain 86.8 cm of the title compound (yield: 72%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

8-chloro-1-(4-(4-(3-chloro2-pyridyl)piperazinyl)butyl) -2,3.

4.5-tetrahydro-1,4-benzoxazepine-
Compound 102■ of 3,5-dione synthesis example 9 was dissolved in dioxane 10d, and 5
8.1 mg (1 equivalent) of 1-(3-chloro-2-pyridyl)piperazine and 122 μg (3 equivalent) of potassium carbonate were added, and the mixture was heated under reflux for 2 days.

The reaction treatment was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain the title compound (86.3) (yield: 63%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

1fi1 8-chloro-4-(4-(4-(3-nitro-2-pyridyl)piperazinyl)butyl)-2,3゜4.5-tetrahydro-1,4-benzoxazepine-3,5- Zeon synthesis C! Compound 121 of Example 9 was dissolved in dioxane 15,
18■ (3 equivalents) of 1-(3-nitro-2-pyridyl)
Piperazine was added and the mixture was heated under reflux for 5 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain the title compound 133 (yield: 80%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

! I! 8-chloro-4-(4-(4-(3-cyano-2-pyridyl)piperazinyl)butyl)-2,3゜4.5-tetrahydro-1,4-benzoxazepine-3,5 - Synthesis of dione i 102 mg of the compound of Example 9 was dissolved in dioxane 10,
55.3 mg (1 equivalent) of 1-(3-cyano-2-pyridyl)piperazine and 122 μm (3 equivalent) of potassium carbonate were added, and the mixture was heated under reflux for 2 days.

The reaction treatment was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain 88.2 mm of the title compound (yield: 66%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

8-chloro-4-(4-(4-(3-amino-2-pyridyl)piperazinyl)butyl) -2,3.

4.5-tetrahydro-1,4-benzoxazepine-
Compound 104 of 3,5-dione synthesis example 9 was dissolved in dioxane]0 m2 and 1
60 ■ (3 equivalents) of 1-(3-amino-2-pyridyl)
Piperazine was added and the mixture was heated under reflux for 17 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain the title compound 116 (yield: 87%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Synthesis of 8-chloro-4-(4-(4-(2-pyrimidinyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione Compound ′jj! of Example 9 IJ98.0■ dioxane 10d
139 μ (3 equivalents) of 1-(2-pyrimidinyl)piperazine was added thereto, and the mixture was heated under reflux for 4 hours.

Reaction treatment was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21.
88.9 µ of the title compound (yield 73%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

8-Methyl-4-(4-(4-(2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1
, 4-benzoxazepine-3,5-dione Synthesis Example 10 Compound 130 was dissolved in 10 ml of dioxane, 196 μ (3 parts) of 1-(2-pyridyl)piperazine was added, and the mixture was heated at 90-100"C. The mixture was stirred for 48 hours.

The title compound 149■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 91.2%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Punishment 8-Methyl-4-(4-(4-(3-chloro-2-pyridyl)piperazinyl)butyl)-2,3゜4.5-tetrahydro-1,4-benzoxazepine-3,5- Compound 130 of Dione Synthesis Example 10 was dissolved in dioxane 10d,
236 μ (3 equivalents) of 1-(3-chloro-2-pyridyl)piperazine was added and the mixture was refluxed for 20 hours.

The title compound 172■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 97.1%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

■Shoulder 8-Methyl-4-(4-(4-(3-nitro-2-pyridyl)piperazinyl)butyl)-2,3°4.5-tetrahydro-1,4-benzoxazepine-3,5 -Dissolving compound 130■ of Dione Synthesis Example 10 in dioxane 10d,
249 μ (3 equivalents) of 1-(3-nitro-2-pyridyl)piperazine were added and the mixture was refluxed for 20 hours.

The title compound 197■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 97.5%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

8-Methyl-4-(4-(4-(3-cyano-2-pyridyl)piperazinyl)butyl)-2,3゜4.5-tetrahydro-1,4-benzoxazepine-3,5 -Dissolving compound 130■ of Dione Synthesis Example 10 in dioxane 10d,
225 μm (3 equivalents) of 1-(3-cyano-2-pyridyl)piperazine was added and the mixture was refluxed for 20 hours.

The title compound 207■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 96.2%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

8-Methyl-4-(4-(4-(3-amino-2-pyridyl)piperazinyl)butyl)-2,3゜4.5-tetrahydro-1,4-benzoxazepine-3,5- Compound 249■ of Dione Synthesis Example 67 was subjected to reaction treatment and purification in the same manner as in Example 57 to obtain the title compound 101■ (yield 48.9%).
I got it. In addition, the hydrochloride is converted into hydrochloride by the usual method, and then
It was recrystallized from ethanol-ether.

Synthesis of 8-methyl-4-(4-(4-(2-pyrimidinyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione Example 0 Compound 130 is dissolved in dioxane 10-,
196 ml (3 parts) of 1-(2-pyrimidinyl)piperazine was added and stirred at 90-100°C for 48 hours.

The title compound 155■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 94.7%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Punishment 8-methoxy-4-(4-(4-(2-pyridyl)piperazinyl)butyl) -2,3,4,5tetrahydro-
Compound 106■ of Synthesis Example 11 of 1,4-benzoxazepine-3°5-dione was dissolved in dioxane 10d,
0.144d (3 equivalents) of 1-(2-pyridyl)piperazine was added and heated under reflux for 5 hours.

The reaction treatment was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain 81.8 cm of the title compound (yield: 62%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Punishment 8-methoxy-4-(4-(4-(2-pyrimidinyl)
(piperazinyl)butyl)-2,3,4°5-tetrahydro-1,4-benzoxazepine-3,5-dione Compound 200 of Synthesis Example 11 was dissolved in dioxane 20d,
288 .mu. (3 equivalents) of 1-(2-pyrimidinyl)piperazine was added and the mixture was heated under reflux for 5 hours.

The reaction treatment was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain the title compound 141 (yield: 57%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

■ Mutual 6-medoxy 4- (4-(4-(2-pyridyl)piperazinyl)butyl)-2,3,4,5tetrahydro-
Compound 55 of Synthesis Example 12 of 1,4-benzoxazepine-3°5-dione was dissolved in dioxane 10, and
．． 0749m (3 equivalents) of 1-(2-pyridyl)piperazine was added and heated to reflux for 7 hours.

Reaction treatment was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21.
64.8 µ of the title compound (yield 95%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Synthesis example 12 of 6-medoxy 4-(4-(4-(2-pyrimidinyl)piperazinyl)butyl)-2,3,4°5-tetrahydro-1,4-benzoxazepine-3,5-dione Compound 60.8μ was dissolved in 10-dioxane, 87.4μ (3 equivalents) of 1-(2-pyrimidinyl)piperazine was added, and the mixture was heated under reflux for 7 hours.

Reaction treatment was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21.
61.0 .mu. (yield: 81%) of the title compound was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

■ Kawara 6-benzyloxy-4-(4-(4-(2-pyridyl)piperazinyl)butyl) -2, 3, 4.

5-tetrahydro-1,4-benzoxazepine 3.5
The title compound 21 was obtained by developing with ethyl acetate using the -dione synthesis graph.
0■ (yield 77%) was obtained. In addition, the maleate salt was made into a maleate salt by a conventional method.

Punishment 6-benzyloxy-4-(4-(4-(2-pyrimidinyl)piperazinyl)butyl) -2,3.

4.5-tetrahydro-1,4-benzoxazepine-
Compound 229 of 3,5-dione synthesis example 13 was dissolved in dioxane 20d,
0.255FJ! (3 equivalents) of 1-(2-pyridyl)
Piperazine was added and the mixture was heated under reflux for 7 hours. Next, dioxane was distilled off, diluted sodium chloride solution was added, and the mixture was extracted with methylene chloride.

This extract was washed with saturated saline and dried over anhydrous magnesium sulfate.Then, the methylene chloride solution was concentrated, and the residue was purified by silica gel column chromatography.Compound 206 of Example 13
■ Dioxane 20! Dissolved in nIl, 242 mg (3
Add 7 equivalents of 1-(2-pyrimidinyl)piperazine.
The mixture was heated to reflux for an hour. The reaction was carried out and purified in the same manner as in Example 75 to obtain the title compound 195 (yield: 79%). In addition, the maleate salt was made into a maleate salt by a usual method.

Synthesis of 6-hydroxy-4-(4-(4-(2-pyridyl)piperazinyl)butyl)-2,3,4,5-titrahydro1,4-benzoxazepine-3,5-dione 10% palladium - Carbon 20.5 ■ Ethyl acetate 5
d was added, the reaction vessel was purged with hydrogen, and the mixture was stirred at room temperature for 30 minutes. Compound 205 of Example 75 dissolved in 5-ethyl acetate was added, and the mixture was stirred at room temperature for 11 hours.

The reaction solution was filtered, the filtrate was evaporated, and the residue was purified using silica gel columnography with hexane-ethyl acetate (1:
2), the title compound 140.mu. (yield: 83%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Synthesis of 6-hydroxy-4-(4-(4-(2-pyrimidinyl)piperazinyl)butyl)-2,3,4°5-tetrahydro-1,4-benzoxazepine-3,5-dione 10 After adding 5 d of ethyl acetate to 23.6 mg of % palladium-carbon and purging the reaction vessel with hydrogen, stirring at room temperature for 30 minutes, 236 mg of the compound of Example 76 dissolved in 5 d of ethyl acetate was added, and the mixture was stirred at room temperature for 17 hours.

The reaction treatment and purification were carried out in the same manner as in Example 77, and the title compound 160
(yield 83%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Open 7-nitro-4-(4-(4-(2-pyridyl)piperazinyl)butyl)-2,3,4,5-tetrahydro-1
, 4-benzoxazepine-3,5-dione Compound 7.2 of Synthesis Example 14 was dissolved in dioxane 3d, and 0
．． 00937 (3 equivalents) of 1-(2-pyridyl)piperazine was added, and the mixture was heated under reflux for 2 hours.

The reaction was carried out in the same manner as in Example 19 and purified in the same manner as in Example 21 to obtain 2.7 mg (yield: 30%) of the title compound. Incidentally, the maleate salt was obtained by converting it into a maleate salt by a conventional method and then recrystallizing it from methylene chloride-ether.

■Synthesis of 7-nitro-4-(4-(4-(2-pyrimidinyl)piperazinyl)butyl)-2,3,4,5tetrahydro-1,4-benzoxazepine=3.5-dione Compound 8.2 of Example 14 was dissolved in dioxane 3-
1.3 (3 equivalents) of 1-(2-pyrimidinyl)piperazine was added and heated under reflux for 4 hours.

The reaction was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain 5.5 cm of the title compound (yield: 54%). Incidentally, the maleate salt was obtained by converting it into a maleate salt by a conventional method and then recrystallizing it from methylene chloride-ether.

Packing 7-Medoxycarbonyl-4-(4-(4-(2-pyridyl)piperazinyl)butyl)-2゜3.4.5-tetrahydro-1,4-benzoxazepine-3,5-dione Compound 60 of Synthesis Example 15 was mixed with dioxane 10In1. 0.0751-(3 equivalents) of 1-(2-pyridyl) dissolved in
Piperazine was added and the mixture was heated under reflux for 8 hours.

The reaction was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain 63.4 cm of the title compound (yield: 87%). Incidentally, the citrate salt was obtained by converting it into citrate salt by a conventional method and then recrystallizing it from methylene chloride-ether.

Kansaku 7-Medoxycarbonyl-4- (4-(4-(2-pyrimidinyl)piperazinyl)butyl) = 2.3, 4.5
-tetrahydro-1,4-benzoxazepine-3,5
- Compound 60 of Dione Synthesis Example 15 was dissolved in Dioxacari Od, and 79
．． 3 mg (3 equivalents) of 1-(2-pyrimidinyl)piperazine was added and the mixture was heated under reflux for 6 hours.

The reaction was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain 53.1■ (yield: 72%) of the title compound. Incidentally, the maleate salt was obtained by converting it into a maleate salt by a conventional method and then recrystallizing it from methylene chloride-ether.

■Synthesis of Village 4- (4-(4-(4-methoxy-2-pyrimidinyl)piperazinyl)butyl)-2,3,4°5-tetrahydro-1,4-benzoxazepine-3,5-dione Compound 326 of Example 7 was dissolved in 20 ml of dioxane,
580 μ (3 equivalents) of a mixture of 1-(4-methoxy-2-pyrimidinyl)piperazine and 1-(2-methoxy-4-pyrimidinyl)piperazine (4:1) was added and the mixture was refluxed for 15 hours.

The title compound 271■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 70.4%). Note that the hydrochloride was converted into a hydrochloride by a conventional method, and then recrystallized from ethanol-ether.

Synthesis of carbon U 4-(4-(4-(2-methoxy-4-pyrimidinyl)piperazinyl)butyl)-2,3,4°5-tetrahydro-1,4-benzoxazepine-3,5-dione From the reaction and purification of Example 83, the title compound 36■ (yield 8.4
%) was obtained. Note that the hydrochloride was converted into a hydrochloride by a conventional method, and then recrystallized from ethanol-ether.

±na4- (4-(4-(2-pyrazinyl)piperazinyl)
butyl) -2,3,4,5-tetrahydro-1,4-
Compound 326 of benzoxazepine-3,5-dione synthesis example 7 was dissolved in dioxane 20d, and 4
Add 92■ (3 equivalents) of 1-pyrazinylpiperazine,
It was refluxed for 20 hours.

The reaction treatment was carried out in the same manner as in Example 23, and the title compound 270 was purified.
(2) (yield 68.3%) was obtained. Note that the hydrochloride was converted into a hydrochloride by a conventional method, and then recrystallized from ethanol-ether.

Counterfeit dish 4- (4-(4-(6-chloro-2-pyrazinyl)piperazinyl)butyl), -2,3,4,5-tetrahydro-1,4-benzoxazepine-3°5-dione Compound 163■ of Synthesis Example 7 was dissolved in dioxane 10d, and 2
98 ■ (1-(6-chloro-2-pyrazinyl) per 3
Piperazine was added and refluxed for 18 hours.

The title compound 194■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 92.8%). Note that the hydrochloride was converted into a hydrochloride by a conventional method, and then recrystallized from ethanol-ether.

■Nail 4- (4-(4-(6-medoxy 2-pyrazinyl)
Compound 130 of Synthesis Example 7 of 2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione (piperazinyl)butyl) was dissolved in dioxane 10d, and 2
32 μm (3 equivalents) of 1-(6-medoxy-2-pyrazinyl)piperazine was added and stirred at 100°C for 20 hours.

The title compound 158■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 92.8%). The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from ethanol-ether.

Compound 70 of Synthesis Example 16 of Baku4-(5-(4-(2-pyridyl)piperazinyl)pentyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine-3,5-dione Dissolve ■ in 10d of dioxane,
．． 167d (5 parts) of 1-(2-pyridyl)piperazine was added, and the mixture was heated and stirred at 100°C for 6 hours.

Reaction treatment was carried out in the same manner as in Example 19, and purification was carried out in the same manner as in Example 21.
79.4 ml of the title compound (yield 91%) was obtained. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

■4- (5-(4-(2-pyrimidinyl)piperazinyl)pentyl) -2,3,4,5-tetrahydro-1,
Compound 70 of Synthesis Example 16 of 4-benzoxazepine-3,5-dione was dissolved in 10 ml of dioxane,
176 µ (5 equivalents) of 1-(2-pyrimidinyl)piperazine was added, and the mixture was heated and stirred at 100°C for 6 hours.

The reaction treatment was carried out in the same manner as in Example 19, and the product was purified in the same manner as in Example 21 to obtain 69.2■ (yield: 79%) of the title compound. The hydrochloride salt was obtained by converting it into a hydrochloride salt using a conventional method and then recrystallizing it from methylene chloride-ether.

Box 7-Medoxy 4- (5-(4-(2-pyridyl)piperazinyl)pentyl)-2,3,4,5=tetrahydro-1,4-benzoxazepine-3,5-dione Synthesis Example 17 Dissolve compound 106■ in dioxane 10d,
147 μm (3 equivalents) of 1-(2-pyridyl)piperazine was added and stirred at 90-100"C for 24 hours.

The title compound 106■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 80.7%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Compound of Synthesis Example 17 of 7-medoxy4-(5-(4-(2-pyrimidinyl)piperazinyl)pentyl)-2,3,4°5-tetrahydro-1,4-benzoxazepine 3.5-dione Dissolve 106■ in dioxane 10d,
147 μm (3 equivalents) of 1-(2-pyrimidinyl)piperazine was added and stirred at 90-100'C for 24 hours.

The title compound 106■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 80.5%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

8-Methyl-4-(5-(4-(2-pyridyl)piperazinyl)pentyl)-2,3,4,5-tetrahydro-
Compound 136■ of Synthesis Example 18 of 1,4-benzoxazepine-3°5-dione was dissolved in dioxa 710d,
200 μ (3 equivalents) of 1-(2-pyridyl)piperazine was added and stirred at 90-ioo'c for 24 hours.

The title compound 154■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield 91.7%). The hydrochloride was converted into a hydrochloride using a conventional method, and then recrystallized from methylene chloride-ether.

Synthesis example of 8-methyl-4-(5-(4-(2-pyrimidinyl)piperazinyl)pentyl)-2,3,4゜5-tetrahydro-1,4-benzoxazepine-3,5-dione 13,611 g of the compound No. 18 was dissolved in dioxane IO-, 200 ml of 1-(2-pyrimidinyl)piperazine was added, and the mixture was stirred at 90-100°C for 24 hours.

The title compound 140■ was obtained by reaction treatment and purification in the same manner as in Example 23.
(yield: 83.1%). The hydrochloride was converted into a hydrochloride by a conventional method and then recrystallized from methylene chloride-ether.

Others 4- (4-(4-(3-acetylamino-2-pyridyl)piperazin-1-ylcobutyl)-2゜3.4.5
-tetrahydro-1,4-benzoxazepine-3,5
Compound 340 (0.8 mM) of -dione synthesis example 69 was dissolved in 10 d of methylene chloride, pyridine 252 (3.3 mM, 4 equivalents) and acetic anhydride 163 mg (1.6 mM, 2 equivalents) were added, and the mixture was heated at room temperature. The mixture was stirred for 3 hours. The solvent was distilled off, ethyl acetate was added, washed with water, and the organic layer was dissolved in magnesium sulfate (anhydrous).
The mixture was dried by filtration, and the solvent was distilled off. The residue was purified using silica gel column chromatography, eluting with ethyl acetate.
102 mg (yield 28%) of the title compound was obtained.

Physical data of the compounds obtained in Examples 19 to 94 are shown in Table 2.

-Koshi1na4- (4-(4-(13-methoxy-2-pyridyl)
Synthesis of (piperazinyl)butyl-2,3,4,5-tetrahydrobenzoxazepine-3,5-dione H, J = 7.9Hz), 6.14 (d, I H
, J=7.9Hz), 7.09 (d, IH.

J=8.2Hz), 7.24(m, I It),
7.39 (t, I H, J = 7.91 (z).

7.5Hm, I H), 8.16(dd, I
H, J = 2.0Hz, 7.9Hz) I R (cm-
'): 2940. 2820. 1710.
1650. 1590°1460.1300,1230
,1150.1120°1040.990,910,7
90,730m, p: 171-174 °C
163 mg of the compound of Example 2 were dissolved in 10 ml of di-sec-xane, 135 mg (1,4 eq.) of 1-(6-medoxy-2-pyridyl)piperazine, 207 mg (3 eq.)
of potassium carbonate was added, and the mixture was refluxed for 16 hours. Treated and purified as in Example 23], 72+++g (81.0%
) was obtained. The hydrochloride was converted into a hydrochloride by a conventional method and recrystallized from ethanol-ether.

'II-N M RT M S CDCf 3)
δ: 1.53 to 1.76 (m, 4 II), 2.4
3 (L, 211.J=7.311z), 2.54
(t, 4 If.

J=4.611z), 3.52 (L, 41f, J
=4.611z), 3.86 (s, 3It).

4.02 (L, 211.J=7.311z), 4.
75 (s, 211), 6.06 (d, 1 [Action/Effects]) The compound of the present invention exhibits strong affinity for serotonin receptors and also exhibits anti-conflict effects, and is effective against anxiety, phobia, It is useful as a therapeutic agent for neuropsychiatric disorders such as obsessive-compulsive neurosis, post-traumatic stress disorder, and depressive neurosis, as well as diseases involving the serotonin nervous system such as eating disorders, menopausal disorders, and childhood autism. Explain the pharmacological test results.

l To serotonin (experimental method) S, T, Perouka (J, Neuroche+++
, 47.529-540 (1986)).

50% in the cerebral cortex removed from Wistar male rats.
Add mM Tris-HCl (pH 7,7) buffer,
Homogenization was performed using a Polytron (Polytron@). This homogenate was heated at 40.000 G to 1
After centrifugation for 0 minutes, the same buffer solution was added to the resulting precipitate for homogenization, and the mixture was incubated at 37°C for 30 minutes. This suspension was again centrifuged at 40,000 G for 10 minutes, the same buffer was added to the resulting precipitate, homogenized, and further centrifuged at 40,00 G for 10 minutes. 50mM Tris-HCji was added to the final precipitate obtained.
! (10mpargyline, 4mMCaCl
z, 0.1% ascorbic acid) (pH 7,4) 1N
It was homogenized by adding street solution and used for binding experiments. The ('H)8-OH Kano AT used in the binding experiment was 0.4 nM, the protein amount was 0.4-0.6 mg/ml, and the total amount was 1 d.
I did it. After incubation for 30 minutes at 25°C, the mixture was filtered using a Whatman GF/B filter and the filter was washed three times with the same buffer 5d. Scintillation cocktail was added to this filter, and measurement was performed using a liquid scintillation counter.

(Test Results) All the compounds of the present invention have strong affinities on the order of μm or less. Substituents on the benzene ring, substituents on the heterocyclic ring,
Among a group of compounds with different types such as the number of carbon atoms in their side chains, the receptor binding abilities of representative compounds are as shown in Table 3, and all had strong affinities on the order of nM.

table hand Continued Supplementary Positive book (spontaneous) 6.15 2.62 2.31 1.41 2.48 2.77 3.75 4.91 5.02 1.78 4.10 1.55 4.75 4.26 4.16 March 20, 1990

Claims (1)

[Claims] 1. General formula (I): ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, A and B are both carbonyl groups, or one is a methylene group and the other is a carbonyl group. group, R represents an optionally substituted aromatic group or heterocyclic group, X is a hydrogen atom, a halogen atom, a C_1 to C_5 lower alkyl group,
A benzoxazepine derivative represented by C_1 to C_5 lower alkoxy group, C_7 to C_9 arylalkoxy group, hydroxyl group, nitro group or ester group, where n is an integer of 2 to 10, and salts thereof. 2. General formula (II): ▲There are mathematical formulas, chemical formulas, tables, etc.▼(II) (In the formula, A and B are both carbonyl groups, or one is a methylene group and the other is a carbonyl group, and X is Hydrogen atom, halogen atom, C_1 to C_5 lower alkyl group, C
_1 to C_5 lower alkoxy group, C_7 to C_9 arylalkoxy group, hydroxyl group, nitro group or ester group, Y represents a halogen atom, and n is an integer of 2 to 10); The salts. 3. A psychotropic agent containing the compound according to claim 1 as an active ingredient. 4. A therapeutic agent for diseases involving the serotonin nervous system, which contains the compound according to claim 1 as an active ingredient.