KR840006253A - Method for preparing fused aromatic oxazine and its sulfur homologue - Google Patents

Abstract

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Description

Fused Aromatic Oxazepine and Sulfur Homologs thereof and Method for Preparing the Same

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Claims (182)

(a) halogenating the compound of formula (IVb) to form a compound of formula (III) or a free base thereof, (b) fusing the resulting compound to generate a compound of formula (IIa), and (c ) Reacting the resulting halogen compound with a compound of the general formula ZH, wherein Z is as defined below, wherein the aromatic or heterocyclic oxazepine tothiazepine of the general formula (I) And methods of preparing pharmaceutically acceptable salts thereof. Wherein A represents an aromatic ring selected from the group consisting of benzene, naphthalene and pyridine, which share two carbon atoms with the oxazepine or thiazepine moiety at any one of the four positions, and optionally any of the halo Is substituted with one or two Y groups selected from the group consisting of lower alkyl, lower alkoxy, nitro and trifluoromethyl; B and E are oxygen or sulfur, may be the same or different and R is hydrogen, lower alkyl, cycloalkyl and phenyl-lower alkyl, wherein phenyl is selected from halo, lower alkyl, lower alkoxy, nitro and trifluoromethyl May be optionally substituted with one or two groups), n is 1,2 or 3, and Z is -NR ¹ R ² , 1H-pyrazol-1-yl or 1H-imidazole-1 -Work; R ¹ and R ² are optionally substituted with one or two groups selected from hydrogen, lower alkyl, cycloalkyl and phenyl-lower alkyl, wherein phenyl is selected from halo, lower alkyl, lower alkoxy, nitro, trifluoromethyl and cyano Or R ¹ and R ² together with adjacent nitrogen atoms are 1-pyrrolidinyl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin-1 -Yl, 1-piperidinyl, 4-substituted piperidin-1-yl, 4-morpholinyl, 1-piperazinyl, 4-substituted piperazin-1-yl and 1,2,3, Can form a heterocycle moiety selected from 6-tetrahydropyridin-1-yl, provided that if R is hydrogen, Z cannot be a primary or secondary amine, and if n is 3, Z is 1H-pyrazole -1-yl, 1H-imidazol-1-yl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin-1-yl or 1,2,3,6-tetrahydropyridine- not a 1-1, R ³ is hydrogen or an acid neutralizing ion, X is Bovine or bromine, provided that in the general formulas (IVb) and (III) A is any one of four positions, selected by one or two Y groups selected from halo, lower alkyl, lower alkoxy, nitro and trifluoromethyl Substituted aromatic, selected from benzene, naphthalene and pyridine, wherein R is lower alkyl, cycloalkyl and phenyl-lower alkyl (wherein phenyl is halo, lower alkyl, lower) Which may be optionally substituted with one or two groups selected from alkoxy, nitro and trifluoromethyl), n is 1 or 2. The method of claim 1 further comprising the step of reacting the compound produced in step (b) with a sulfiding agent to obtain azepinthione of formula (IIb). Wherein A is one or two selected from the group consisting of halo, lower alkyl, lower alkoxy, nitro and trifluoromethyl, which share two carbon atoms with the oxazepine or thiazepine moiety at any one of the four positions Y represents an aromatic ring selected from the group consisting of benzene, naphthalene and pyridine, optionally substituted with Y, wherein E is oxygen or sulfur and may be the same or different, and R is lower alkyl, cycloalkyl and phenyl-lower alkyl (of which , Phenyl may be optionally substituted with one or two groups selected from halo, lower alkyl, lower alkoxy, nitro and trifluoromethyl), n is 1 or 2 and X is chlorine or bromine . The compound of claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or a pharmaceutical thereof. Salts that are acceptable. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (4-morpholino) ethyl] -1,4-benzoxazepin-5 (4H) -one Or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the prepared compound is 4-benzyl-2,3-dihydro-2- [2- (4-morpholino) ethyl] -1,4-benzoxazepin-5 (4H) -one Or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 4-benzyl-2,3-dihydro-2- [2- (methylamino) ethyl] -1,4-benzoxazepin-5 (4H) -one or a pharmaceutical thereof. Salts that are acceptable. The compound according to claim 2, wherein the compound prepared is 2- [2- (methylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -thione or a pharmaceutical thereof. Salts that are acceptable. The compound of claim 2, wherein the compound prepared is 4-benzyl-2- [2- (dimethylamino) ethyl] -2,3-dihydro-1,4-benzoxazepin-5 (4H) -one or a pharmaceutical thereof. Salts that are acceptable. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (4-morpholino) ethyl] -1,4-benzoxazepin-5 (4H) -thione Or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2 is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylnaphth [2,3-f] [1,4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2 is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2 is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 4-benzyl-2,3-dihydro-2- [2- (4-morpholino) ethyl] 1,4-benzoxazepin-5 (4H) -thione or It is a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is -2,3-dihydro-4-methyl-2- [2- (methylamino) ethyl] 1,4-benzoxazepin-5 (4H) -one or a pharmaceutical thereof. Salts that are acceptable. The compound prepared according to claim 2, wherein the compound prepared is 2,3-dihydro-2- [2- (4-hydroxy-4-phenyl) piperidinylethyl] -4-methyl-1,4-benzoxazepine- 5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is -2,3-dihydro-4-methyl-2- [1- (4-fetyl-1,2,2,3,6-tetrahydro) pyridinyl) ethyl] -1,4-benzoxazepine-5 (4H) -thione or a pharmaceutically acceptable salt thereof. 3. The compound of claim 2, wherein the compound prepared is 8-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H). -Thione or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the prepared compound is 8-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H)- Thion or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 7-bromo-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H). -Thione or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylnaphth [2,1-f] [1,4] oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [4,3-f] [1,4] -oxazepine- 5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylnaphth [2,3-f] [1,4] -oxazepine- 5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 7-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-oxazepin-5 (4H) -one Or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] oxazepine-5 (4H) -thione metiodide. The compound prepared according to claim 2, wherein the compound prepared is 7-chloro-2- (2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H)- Thion or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylnaphth [21-f] [1,4] oxazepine-5 (4H ) -Thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepin-5 (4H). -One or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 7-bromo-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H). -Thione or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -thiazepine- 5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -thiazepine- 5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,4-f] [1,4] -oxazepine- 5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,4-f] [1,4] -oxazepine- 5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 1 wherein the compound prepared is 2- (3-aminopropyl) -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H ) -One or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (4-morpholinyl) ethyl] -pyrido [3,2-f] [1,4] Oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (1-pyrrolidinyl) ethyl] -pyrido [3,2-f] [1,4] Oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dibutylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine -5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (1-piperidinyl) ethyl] -pyrido [3,2-f] [1,4] Oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (methyl (phenylmethyl) amino] ethyl] pyrido [3,2-f] [1,4] Oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (methylphenylamino) ethyl] -pyrido [3,2-f] [1,4] -oxazepine -5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2- [2- (2,5-dimethyl-1-pyrrolidinyl) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (2-methyl-1-pyrrolidinyl) ethyl] -pyrido [3,2-f] [ 1,4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (1H-pyrazol-1-yl) ethyl] pyrido [3,2-f] [1, 4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-2- [2- (1H-imidazol-1-yl) ethyl] -4-methylpyrido [3,2-f] [1, 4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -4-ethyl-2,3-dihydropyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the prepared compound is 2,3-dihydro-4-ethyl-2- [2- (1-pyrrolidinyl) ethyl] pyrido [3,2-f] [1,4]- Oxazin-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2,3-dihydro-4-ethyl-2- [2- (4-morpholinyl) ethyl] pyrido [3,2-f] [1,4]- Oxazepine-5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dibutylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine -5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2- [2- (diethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine -5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- (1-pyrrolidinyl) ethyl] -pyrido [3,2-f] [1,4] Oxazepine-5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-2- [2- (1H-imidazol-1-yl) ethyl] -4-methylpyrido [3,2-f] [1, 4] -oxazepine-5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -4-ethyl-2,3-dihydropyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 2,3-dihydro-4-methyl-2- [2- [methyl (phenylmethyl) amino] ethyl] pyrido [3,2-f] [1,4] Oxazepine-5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2,3-dihydro-2- [2- (methylamino) ethyl] -4-methylpyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 7-chloro-2,3-dihydro-4-methyl-2- [2- (1-pyrrolidinyl) ethyl] pyrido [3,2-f] [1 , 4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 7-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] Oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-phenylmethylpyrido [3,2-f] [1,4] -oxazepine -5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [2- (dimethylamino) ethyl] -2,3-dihydropyrido [3,2-f] [1,4] -oxazepine-5 (4H) -One or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 2, wherein the compound prepared is 2- [3- (dimethylamino) propyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine -5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound prepared according to claim 1, wherein the compound prepared is 2- [3- (dimethylamino) propyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -thione or a pharmaceutically acceptable salt thereof. The compound of claim 2, wherein the compound prepared is 7-chloro-2- [2- (diethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4 ] -Oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. (a) halogenating the compound of general formula (IVb) to form an acid halide or a free base thereof, and (b) fusion of the resulting compound, A process for preparing aromatic or heterocyclic oxazepines and acid addition salts thereof. Wherein A represents an aromatic or heterocyclic ring selected from the group consisting of benzene, naphthalene and pyridine, which share two carbon atoms with the oxazepine or thiazepine moiety at any one of the four positions, Is optionally substituted with one or two Y groups selected from the group consisting of halo, lower alkyl, lower alkoxy, nitro and trifluoromethyl, provided that in general formulas (IVb) and (III) the two carbon atoms of A Or is not bound to a thiazine ring, B and E are oxygen or sulfur, and may be the same or different, and R is lower alkyl, cycloalkyl and phenyl-lower alkyl, wherein phenyl is halo, lower alkyl, lower alkoxy, nitro And optionally substituted with one or two groups selected from trifluoromethyl), M is 1 or 2, and X is In cattle, a bromine, or cyano, with the proviso that formula (III) is a chlorine or bromine, R ³ is hydrogen or an acid neutralizing ion. 63. The method of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or acid addition salt. 63. The method of claim 62, wherein the compound prepared is 4-benzyl-2- (2-chloroethyl) -2,3-dihydro-1,4-benzoxazepin-5 (4H) -one or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylnaphth [2,3-f] [1,4] -oxazepine-5 (4H ) -One or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H ) -One or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 8-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or acid moiety. How to be salted. 63. The compound of claim 62, wherein the compound prepared is 7-bromo-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or Acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 7-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or acid moiety. How to be salted. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylnaphth [2,1f] [1,4] -oxazepine-5 (4H)- Warm or acid addition salts. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-8-methoxy-4-methyl-1,4-benzoxazepin-5 (4H) -one or Acid addition salt. 63. The method of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H ) -Thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylnaphth [2,3-f] [1,4] -oxazepine-5 (4H ) -Thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 8-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -thione or acid moiety. How to be salted. 63. The compound of claim 62, wherein the compound prepared is 7-bromo-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-oxazepine-5 (4H) -thione or acid moiety. How to be salted. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylnaphth- [2,1-f] [1,4] -oxazepine-5 ( 4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylnaphth- [4,3-f] [1,4] -oxazepine-5 ( 4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 7-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -thione or acid moiety. How to be salted. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido- [4,3-f] [1,4] -oxazepine-5 ( 4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepin-5 (4H) -thione or Acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido- [3,2-f] [1,4] -thiazepine-5 ( 4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido- [3,2-f] [1,4] -thiazepine-5 ( 4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido- [3,4-f] [1,4] -oxazepine-5 ( 4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido- [3,4-f] [1,4] -oxazepine-5 ( 4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2,3,4,5-tetrahydro-4-methyl-5-oxopyrido- [3,2-f] [1,4] -oxazepine-2-propane Nitrile or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -4-ethyl-2,3-dihydropyrido- [3,2-f] [1,4] -oxazepine-5 ( 4H) -one or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -4-ethyl-2,3-dihydropyrido- [3,2-f] [1,4] -oxazepine-5 ( 4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 7-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido- [3,2-f] [1,4] -oxa Zepin-5 (4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 7-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido- [3,4-f] [1,4] -oxa Zepin-5 (4H) -thione or acid addition salt. 63. The compound of claim 62, wherein the compound prepared is 2- (2-chloroethyl) -4-cyclohexyl-2,3-dihydro-pyrido [3,2-f] [1,4] -oxazepine-5 (4H) -thione or acid addition salt. A compound selected from the group of formula (I) and a pharmaceutically acceptable salt thereof. Wherein A represents an aromatic ring selected from the group consisting of benzene, naphthalene and pyridine, which share two carbon atoms with the oxazepine or thiazepine moiety at any one of the four positions, and optionally any of the halo Is substituted with one or two Y groups selected from the group consisting of lower alkyl, lower alkoxy, nitro and trifluoromethyl; B and E are oxygen or sulfur, can be the same or different, and R is hydrogen, loweralkyl, cycloalkyl and phenyl-loweralkyl (where phenyl is halo, loweralkyl, loweralkoxy, nitro and trifluoromethyl Optionally substituted with one or two groups selected), n is 1,2 or 3, and Z is -NR ¹ R ² , 1H-pyrazol-1-yl or 1H-imidazole- 1-day; R ¹ and R ² are optionally substituted with one or two groups selected from hydrogen, lower alkyl, cycloalkyl and phenyl-lower alkyl, wherein phenyl is selected from halo, lower alkyl, lower alkoxy, nitro, trifluoromethyl and cyano Or R ¹ and R ² together with adjacent nitrogen atoms are 1-pyrrolidinyl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin-1 -Yl, 1-piperidinyl, 4-substituted piperidin-1-yl, 4-morpholinyl, 1-piperazinyl, 4-substituted piperazin-1-yl and 1,2,3, Or heterocycle moiety selected from 6-tetrahydropyridin-1-yl, provided that when R is hydrogen, Z cannot be a primary or secondary amine, and if n is 3, Z is 1H-pyrazole -1-yl, 1H-imidazol-1-yl, 2,5-dimethylpyrrolidin-1-yl, 2-methylpyrrolidin-1-yl or 1,2,3,6-tetrahydropyridine- It is not one-day. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or a pharmaceutically acceptable thereof. Salts. 92. The method of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (4-morpholino) ethyl] -1,4-benzoxazepin-5 (4H) -one or a pharmaceutical thereof Compounds that are acceptable salts. 92. The method of claim 92, wherein 4-benzyl-2,3-dihydro-2- [2- (4-morpholino) ethyl] -1,4-benzoxazepin-5 (4H) -one or a pharmaceutical thereof Compounds that are acceptable salts. 92. The compound of claim 92, wherein 4-benzyl-2,3-dihydro-2- [2- (4-methylamino) ethyl] -1,4-benzoxazepin-5 (4H) -one or a pharmaceutically thereof Compounds that are acceptable salts. 95. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -thione or a pharmaceutically acceptable thereof Salts. 93. The compound of claim 92, wherein 4-benzyl-2- [2- (dimethylamino) ethyl] -2,3-dihydro-1,4-benzoxazepin-5 (4H) -one or a pharmaceutically acceptable thereof. Salts. 92. The compound of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (4-morpholino) ethyl] 1,4-benzoxazepin-5 (4H) -thione or pharmaceutically thereof Compounds that are acceptable salts. 95. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylnaphth [2,3, -f] [1,4] -oxazepine-5 (4H ) -Thione or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [2,3, -f] [1,4] -oxazepine-5 (4H ) -One or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [2,3, -f] [1,4] -oxazepine-5 (4H ) -Thione or a pharmaceutically acceptable salt thereof. 93. The method of claim 92, wherein 4-benzyl-2,3-dihydro-2- [2- (4-morpholino) ethyl] -1,4-benzoxazepine-5 (4H) -thione or a pharmaceutical thereof Compounds that are acceptable salts. 93. The compound of claim 92, which is 2.3-dihydro-4-methyl-2- [2- (methylamino) ethyl] -1,4-benzoxazepin-5 (4H) -one or a pharmaceutically acceptable salt thereof. . 92. The method of claim 92, wherein 2,3-dihydro-2- [2- (4-hydroxy-4-phenyl) piperidinylethyl] -4-methyl-1,4-benzoxazepin-5 (4H) -One or a pharmaceutically acceptable salt thereof. 92. The compound of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (4-phenyl-1,2,3,6-tetrahydro) pyridinyl] ethyl] -1,4-benzoxa Zepin-5 (4H) -thione or a pharmaceutically acceptable salt thereof. 95. The compound of claim 92, wherein 8-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -thione or a pharmaceutical thereof Compound which is a permissible salt. 92. The method of claim 92, wherein 8-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or a pharmaceutical thereof Compound which is a permissible salt. 93. The compound of claim 92, wherein 7-bromo-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepine-5 (4H) -thione or thereof A compound that is a pharmaceutically acceptable salt. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylnaphth [2,1-f] [1,4] -oxazepine-5 (4H) -One or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylnaphth [4,3-f] [1,4] -oxazepine-5 (4H) -Thione or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylnaphth [2,3-f] [1,4] -oxazepine-5 (4H) -Thione or a pharmaceutically acceptable salt thereof. 95. The compound of claim 92, wherein 7-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or a pharmaceutical thereof Compound which is a permissible salt. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -Thione metiodyne compound. 95. The compound of claim 92, wherein 7-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or a pharmaceutical thereof Compound which is a permissible salt. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylnaphth [2,1-f] [1,4] -oxazepine-5 (4H) -Thione or a pharmaceutically acceptable salt thereof. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepin-5 (4H) -one or its A compound that is a pharmaceutically acceptable salt. 93. The compound of claim 92, wherein 7-bromo-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methyl-1,4-benzoxazepine-5 (4H) -thione or thereof A compound that is a pharmaceutically acceptable salt. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -thiazepine-5 (4H) -One or a pharmaceutically acceptable salt thereof. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -thiazepine-5 (4H) -Thione or a pharmaceutically acceptable salt thereof. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -One or a pharmaceutically acceptable salt thereof. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -Thione or a pharmaceutically acceptable salt thereof. 92. The compound of claim 92, wherein 2- (3-aminopropyl) -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazin-5 (4H) -one or Compounds which are pharmaceutically acceptable salts thereof. 92. The composition of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (4-morpholinyl) ethyl] -pyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -one or a pharmaceutically acceptable salt thereof. 92. The compound of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (1-pyrrolidinyl) ethyl] -pyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -one or a pharmaceutically acceptable salt thereof. 92. The compound of claim 92, wherein 2- [2- (dibutylamino) ethyl] 2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazinpin-5 (4H) -One or a pharmaceutically acceptable salt thereof. 93. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -One or a pharmaceutically acceptable salt thereof. 93. The compound of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (1-piperidinyl) ethyl] pyrido [3,2-f] [1,4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. 92. The composition of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- [methyl (methylmethyl) amino] ethyl] pyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -one or a pharmaceutically acceptable salt thereof. 92. The method of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (methylphenylamino) ethyl] pyrido [3,2-f] [1,4] -oxazepine-5 (4H) -One or a pharmaceutically acceptable salt thereof. 93. The compound of claim 92 wherein 2- [2- (2,5-dimethyl-1-pyrrolidinyl) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4 ] -Oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. 92. The method of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (2-methyl-1-pyrrolidinyl) ethyl] pyrido [3,2-f] [1,4]- Oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. 92. The compound of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (1H-pyrazol-1-yl) ethyl] pyrido [3,2-f] [1,4] -oxa Zepin-5 (4H) -one or a pharmaceutically acceptable salt thereof. 92. The compound of claim 92, wherein 2,3-dihydro-2- [2- (1H-imidazol-1-yl) ethyl] -4-methylpyrido [3,2-f] [1,4] -oxa Zepin-5 (4H) -one or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -4-ethyl-2,3-dihydro-4-pyrido [3,2-f] [1,4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. 92. The compound of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (1-pyrrolidinyl-ethyl] pyrido [3,2-f] [1,4] -oxazepine-5 (4H) -one or a pharmaceutically acceptable salt thereof. 92. The compound of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (4-morpholinyl-ethyl] pyrido [3,2-f] [1,4] -oxazepine-5 (4H) -thione or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (dibutylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H ) -Thione or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (diethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H ) -Thione or a pharmaceutically acceptable salt thereof. 93. The compound of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (1-pyrrolidinyl) ethyl] pyrido [3,2-f] [1,4] -oxazepine-5 (4H) -thione or a pharmaceutically acceptable salt thereof. 92. The compound of claim 92, wherein 2,3-dihydro-2- [2- (1H-imidazol-1-yl) ethyl] -4-methylpyrido [3,2-f] [1,4] -oxa Zepin-5 (4H) -thione or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -4-ethyl-2,3-dihydropyrido [3,2-f] [1,4] -oxazepine-5 (4H) -Thione or a pharmaceutically acceptable salt thereof. 92. The composition of claim 92, wherein 2,3-dihydro-4-methyl-2- [2- (methyl (phenylmethyl) amino] ethyl] pyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -thione or a pharmaceutically acceptable salt thereof. 92. The method of claim 92, wherein 2,3-dihydro-2- [2- (methylamino) ethyl] -4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -Thione or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 7-chloro-2,3-dihydro-4-methyl-2- [2-(-1pyrrolidino) ethyl] -pyrido [3,2-f] [1,4] An oxazin-5 (4H) -one or a pharmaceutically acceptable salt thereof. 95. The compound of claim 92, wherein 7-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -one or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-phenylmethylpyrido [3,2-f] [1,4] -oxazepine-5 (4H ) -One or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [2- (dimethylamino) ethyl] -2,3-dihydropyrido [3,2-f] [1,4] -oxazin-5 (4H) -one or its A compound that is a pharmaceutically acceptable salt. 94. The compound of claim 92, wherein 2- [3- (dimethylamino) propyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -One or a pharmaceutically acceptable salt thereof. 94. The compound of claim 92, wherein 2- [3- (dimethylamino) propyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -Thione or a pharmaceutically acceptable salt thereof. 95. The compound of claim 92, wherein 7-chloro-2- [2- (dimethylamino) ethyl] -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine- 5 (4H) -one or a pharmaceutically acceptable salt thereof. The compound of formula (II) and acid addition salts thereof. Wherein A represents an aromatic or heterocyclic ring selected from the group consisting of benzene, naphthalene and pyridine, which share two carbon atoms with the oxazepine or thiazepine moiety at any one of the four positions Some are optionally substituted with one or two Y groups selected from the group consisting of halo, lower alkyl, lower alkoxy, nitro and trifluoromethyl; B and E are oxygen or sulfur and may be the same or different; R consists of lower alkyl, cycloalkyl and phenyl-lower alkyl, wherein phenyl may be optionally substituted with one or two groups selected from the group consisting of halo, lower alkyl, lower alkoxy, nitro and trifluoromethyl Selected from the group, n is 1 or 2; X is chlorine, bromine or cyano. 152. The compound of claim 152, which is 2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or an acid addition salt thereof. 152. The compound of claim 152, which is 4-benzyl-2- (2-chloroethyl) -2,3-dihydro-1,4-benzoxazepin-5 (4H) -one or an acid addition salt thereof. 153. The 2- (2-chloroethyl) -2,3-dihydro-4-methylnaphth- [2,3-f] [1,4] -oxazin-5 (4H) -one according to claim 152. Or acid addition salts thereof. 152. The 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido- [3,2-f] [1,4] -oxazin-5 (4H) -one according to claim 152. Or acid addition salts thereof. 152. The compound of claim 152, which is 8-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or an acid addition salt thereof. . 152. The compound of claim 152, which is 7-bromo-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or an acid addition salt thereof. compound. 152. The compound of claim 152, which is 7-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -one or an acid addition salt thereof. . 152. The compound of claim 152, wherein 2- (2-chloroethyl) -2,3-dihydro-4-methylnaphth [2,1-f] [1,4] -oxazin-5 (4H) -one or Its acid addition salt. 152. The compound of claim 152 which is 2- (2-chloroethyl) -2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepin-5 (4H) -one or an acid addition salt thereof. compound. 152. The compound of claim 152, which is 2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepine-5 (4H) -thione or an acid addition salt thereof. 152. The compound of claim 152, wherein 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] -oxazepine-5 (4H) -thione or Its acid addition salt. 152. The compound of claim 152, wherein 2- (2-chloroethyl) -2,3-dihydro-4-methylnaphth [2,3-f] [1,4] -oxazepine-5 (4H) -thione or Its acid addition salt. 152. The compound of claim 152, which is 8-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepin-5 (4H) -thione or an acid addition salt thereof. . 152. The compound according to claim 152, which is 7-bromo-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepine-5 (4H) -thione or an acid addition salt thereof. compound. 152. The compound of claim 152, wherein 2- (2-chloroethyl) -2,3-dihydro-4-methylnaphth [2,1-f] [1,4] -oxazepine-5 (4H) -thione or Its acid addition salt. 152. The 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [4,3-f] [1,4] oxazepine-5 (4H) -thione or the same thereof. Hydrochloride or acid addition salt. 152. The compound of claim 152, which is 7-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methyl-1,4-benzoxazepine-5 (4H) -thione or an acid addition salt thereof. . 152. The 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [4,3-f] [1,4] oxazepine-5 (4H) -thione or the same thereof. Acid addition salts. 152. The compound according to claim 152, which is 2- (2-chloroethyl) -2,3-dihydro-7-methoxy-4-methyl-1,4-benzoxazepine-5 (4H) -thione or an acid addition salt thereof. compound. 152. The compound of claim 152, wherein 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [4,3-f] [1,4] thiazepin-5 (4H) -one or Acid addition salts. 152. The compound of claim 152, wherein 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] thiazepine-5 (4H) -thione or Acid addition salts. 152. The compound of claim 152, wherein 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [3,4-f] [1,4] oxazepin-5 (4H) -one or its Acid addition salts. 152. The compound of claim 152, wherein 2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [3,4-f] [1,4] oxazepin-5 (4H) -one or its Acid addition salts. 152. The compound according to claim 152, which is 2,3,4,5-tetrahydro-4-methyl-5-oxopyrido [3,2-f] [1,4] oxazepine-2-propanenitrile or an acid addition salt thereof. compound. 152. The compound of claim 152, wherein 2- (2-chloroethyl) -4-ethyl-2,3-dihydropyrido [3,2-f] [1,4] oxazepin-5 (4H) -one or its Acid addition salts. 152. The compound of claim 152, wherein 2- (2-chloroethyl) -4-ethyl-2,3-dihydropyrido [3,2-f] [1,4] oxazepin-5 (4H) -one or its Acid addition salts. 152. The method of claim 152, wherein 7-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] oxazepine-5 (4H) -One or an acid addition salt thereof. 152. The method of claim 152, wherein 7-chloro-2- (2-chloroethyl) -2,3-dihydro-4-methylpyrido [3,2-f] [1,4] oxazepine-5 (4H) -Thione or an acid addition salt thereof. 152. The 2- (chloroethyl) -4-cyclohexyl-2,3-dihydropyrido [3,2-f] [1,4] oxazepin-5 (4H) -one or its acid moiety according to claim 152. Compound that is soluble. 63. The method of claim 62, further comprising the step of reacting the compound produced in step (b) with a sulfiding agent to obtain an oxazetpinion or thiazepinthione of formula (IIb). Wherein A, E, R, X, Y and n are as defined in claim 62. ※ Note: The disclosure is based on the initial application.