FI64582C - FOERFARANDE FOR FRAMSTAELLNING AV FOER BEHANDLING AV AGITATIONSTILLSTAOND LAEMPLIGA 1,2,3,4,5,10-HEXAHYDRO-DIBENSO- (3,4: 6,7) CYCLOHEPTA (1,2-D) AZEPINER OCH ANALOGER MED -O- - S- ELLER -NR3- I 10-STAELLNINGEN - Google Patents

Description

I- -.— - · Ι Γβ1 NOTICE OF PUBLICATION ^ Λ _ UTLÄGCNINGSSKRI FT 64 5 8 2 ^ —y— '(51) Kv.ik.?int.ci.C 07 D 223/32, 487/04, 491/044 , 495/04 FINLAND I - FINLAND (21) Pttenttlhikemu * - Patentansttknlng 771651 (22) H »Kemi * pllvS —Aniöknlnpdag 24.05.77 ^) (23) AlkupUvft - Glltlghetsdag 24.05.77 (41) Has become public - Bllv't off 27 11 77

Patent and Registration Office »(44) Date of issue of the publication. -

Patent- och registerstyrelsen Ansökan utlagd och utl.skrlften ptibllcerad 31.0o.oj (32) (33) (31) Requested priority - Begird priority 26.05.76

Swiss-Swiss (CH) 6650/76 (71) Ciba-Geigy AG, Klybeckstrasse 141, CH-4002 Basel, Swiss-Swiss (CH) (72) Hans Balttner, Riehen, Angelo Stomi, Rheinfelden, Swiss-Swiss (CH) (74) Cy Jalo Ant-Wuorinen Ab (54) Method for treating boiling conditions with suitable 1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclhepta (1,2-d) for the preparation of azepines and analogues containing the group -O-, -S- or -NR_- in the 10-position - For the preparation of fractions of the group consisting of 1,2,3,4,5,10-hexahydro-dibenzo (3,4: The present invention relates to a process for the preparation of novel azatetracycles with acidic pharmacological properties and their acid addition salts of the following formula: 6,7) is? 1 Cl - 0Q> wherein hydrogen is lower alkyl of up to 6 carbon atoms, cycloalkyl lower alkyl of up to 10 carbon atoms, lower alkenyl of up to 8 carbon atoms.

2 64582 lower alkynyl of up to 4 carbon atoms, lower lower alkylamino of up to 10 carbon atoms, hydroxy-lower alkyl of up to 8 carbon atoms, lower alkoxy-lower alkyl of up to 10 carbon atoms; , and R 2 represents hydrogen, chlorine, bromine, lower alkyl of up to 3 carbon atoms, hydroxy, lower alkoxy of up to 3 carbon atoms, lower alkylthio of up to 3 carbon atoms, or cyano, X represents epoxy, epithio, methylene, or a divalent residue having the structure \ /

OF

'(Ia) R 3 wherein represents hydrogen or lower alkyl having up to 4 carbon atoms, and for the preparation of their acid addition salts.

Acid addition salts of the compounds of formula I are especially pharmaceutically acceptable acid addition salts.

As cycloalkyl lower alkyl, the residue R 1 preferably contains 4 to 8 carbon atoms. Cycloalkyl-lower alkyl is thus e.g. cyclopropylmethyl, cyclobutylmethyl and especially cyclopentylmethyl, cyclohexylmethyl, further e.g. cyclopropylethyl, cyclobutylethyl, cyclopentylethyl, cyclohexylethyl.

As lower alkenyl, the residue R 1 preferably contains 3-4 carbon atoms, and especially 3 carbon atoms. Lower alkenyl is e.g. allyl or 2-methallyl.

The lower alkynyl is a residue R 1, especially propargyl.

In the radical R 1, this being a lower dialkylamino lower alkyl, the nitrogen atom is separated by at least two carbon atoms from the ring nitrogen atom. This residue contains in particular 4 to 6 carbon atoms. Lower alkyl radicals in this substituent are preferably straight-chain. The whole residue is, for example, diethylaminobutyl, propyl or ethyl, dimethylaminobutyl, ethyl and especially dimethylaminopropyl.

3,64582 When the residue is hydroxy-lower alkyl, the hydroxyl group is separated by at least two carbon atoms and a ring nitrogen atom.

This residue contains 2-8 and preferably 2-6 carbon atoms. Hydroxy lower alkyl, which may be straight-chain or branched, is, for example, 1-methyl-2-hydroxyethyl, 2-hydroxypropyl, 1- or 2-methyl-2-hydroxypropyl, and in particular 2-hydroxyethyl and 3- hydroxypropyl.

When the residue is lower alkoxy lower alkyl, the oxygen atom is separated by at least two carbon atoms from the ring nitrogen atom. This residue preferably contains 3 to 6 carbon atoms. This lower alkoxy lower alkyl is e.g. 2-methoxypropyl, 2- or 3-ethoxypropyl, 2- or 3-propoxypropyl, 3-isopropoxypropyl and in particular 2-methoxy or 2-ethoxyethyl and in particular 3-methoxypropyl .

When the residue R 1 is alkanoyloxy lower alkyl, the oxygen atom is separated from the ring nitrogen atom by at least two carbon atoms. This residue preferably contains 4 to 11 carbon atoms. This residue is, for example, 2-formyloxy-ethyl, 2-acetyloxy-ethyl, 2-propionyloxy-ethyl, 2-acetyloxy-propyl, 2-methyl-3-acetyloxy-propyl or 2- or 3-propionyloxy-propyl and in particular 3 -acetyloxypropyl and 3-octanoyloxypropyl.

In the lower alkylthio lower alkyl residue R 1, the sulfur atom is separated by at least two carbon atoms from the ring nitrogen atom. This residue preferably contains 3 to 6 carbon atoms. Such lower alkylthioalkylalkyl is especially methylthioethyl or 3-methylthiopropyl.

Rj is lower alkyl having up to 3 carbon atoms, e.g. ethyl, propyl, isopropyl, especially methyl, and lower alkoxy having up to 3 carbon atoms, e.g. ethoxy, propoxy, isopropoxy, especially methoxy, and lower alkylthio having up to 3 carbon atoms, e.g. ethylthio, propylthio, isopropyl , especially methylthio.

When X denotes a divalent residue with structure \ /

OF

'(Ia) R 3 is R 1 hydrogen or lower alkyl having up to 4 carbon atoms, such as propyl, butyl, isobutyl and above all methyl or ethyl.

From our patent publications 50,629, 50,982 and 50,983 FI, compounds are known which contain a pyrrolidine ring (5-ring) instead of an azepine ring (7-ring) and which have, for example, a central nervous system suppressing effect. On the other hand, DE-A-25 03 407 discloses compounds which contain a piperidine ring, i.e. a 6-ring, and which thus represent a technique closer to the compounds of the present invention than the above-mentioned 5-ring compounds. However, the properties of the compounds known from the DE application are opposite to those of the invention, so that the closest prior art is likely to lead away from the invention, and the depressant effect of the azepine compounds of the invention is very surprising compared to this publication.

Salts of the compounds of the formula I are preferably acid addition salts, in particular pharmaceutically acceptable acid addition salts, e.g. -hydroxyethanesulfonic acid, acetic acid, malic acid, tartaric acid, citric acid, lactic acid, oxalic acid, succinic acid, fumaric acid, maleic acid, benzoic acid, salicylic acid, phenylacetic acid, mandelic acid or embonic acid.

The novel azatetracycles of the general formula I and their acid addition salts have valuable pharmacological properties, e.g. acting on the central nervous system. They are characterized primarily by central nervous system depressant, accelerator-relieving (amphetamine-antagonistic) effects, which can be demonstrated by pharmacological experiments. Thus, they have an anti-acceleration effect in the rat amphetamine antagonist test (Niemegeers and Janssen, Arz-neimittelforsch,. Bd. 24, p. 45 (1974)) at a dose of 0.1-25 mg / kg i-p. it is per os. The cataleptic effect is relatively small compared to the amphetamine antagonist effect. The novel azatetracycles of general formula I and their pharmaceutically acceptable acid addition salts can thus be used as sedatives, antipsychotics and accelerators to treat acceleration conditions.

5,64582

Pharmacological action

Amphetamine antagonistic effect in the rat

Yhdiste_____j. p.-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) -3-azepine methanesulfonate 0.7 3-methyl-2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7} -oxepino (4,5-diazepine hydrochloride 0.55 3-ethyl-2,3,4, 5-Tetrahydro-1H-dibenzo- (3,4: 6,7) -cyclohepta (1,2-d) azepine methanesulfonate 1,4-methyl-1,2,3,4,5,10-hexahydro- Dibenzo (b, f} -azepino (4,5-d) azepine methanesulfonate 0,7 3-Methyl-2,3,4,5-tetrahydro-1H-dibenzo (3,4: 6,7) -cyclohepta (1,2-d) Azepine methanesulfonate hemihydrate 0.6 3-Methyl-7-chloro-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4 .5-d) azepine hydrochloride 0.16 3-cyclopentylmethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thienpino (4,5-d) azepine methanesulfonate 1, 3- (2,3,4,5-Tetrahydro-1H-dibenzo (2,3: 6,7) thiepino- (4,5-d) azepin-3-yl) propanol methanesulfonate 1,2 3 -methyl 7-cyano-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine methanesulfonate 0.18 3,10-dimethyl- 1,2,3,4,5,10-hexahydro-dibenzo (b, f) Azepino (4,5-d) azepine methanesulfonate 0.7 7-chloro-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) oxepino (4,5-d) azepine hydrochloride 0.08 3-Cyclopentylmethyl-7-cyano-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5- d) azepine methanesulfonate 0.75

The invention relates in particular to compounds of the formula I in which R 1 represents lower alkyl, e.g. methyl or ethyl, or cyclopentylmethyl, and R 2 represents chlorine, methyl, methoxy or cyano, and is in particular in the 7-position, X represents epoxy, epithio or methylene or a bivalent residue with a structure of \ /? (Ia) R 3 wherein R 1 represents hydrogen, methyl or ethyl, such as 3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine 1,3-methyl-6,64582 2,3,4,5-tetrahydro-1H-dibenzo (3,2: 6,7) oxepino (4,5-d) azepine, 3-methyl ”7-cyano-2,3 , 4,5-tetrahydro-1H-dibenzo (3,2: 6,7) thiepino (4,5-d) -azepine, 3-methyl-1,2,3,4,5,10-hexahydro-dibenzo ( 3,4: 6,7) cyclohepta (1,2-d) azepine or 3- (2,3,4,5-tetrahydro-1H-dibenzo (3,2: 6,7) -thiepine (4, 5-d) azepin-3-yl) -propanol, as well as its salts, in particular its acid addition salts, in particular pharmaceutically acceptable acid addition salts.

The compounds of the formula I are prepared in a manner known per se. Thus, for example, they are obtained by reacting a reactive diester of diethanol with the formula ethanol

E-CH- CH - E

i 4 \ £ CH0 CH,

A i | II

wherein E represents an acid residue of a strong inorganic or organic acid is reacted with a compound of formula? N 111 X \

Ά H

As the reactive diester of the diethanol of the formula II, esters of strong inorganic acids can be used, such as, for example, bis-hydrochloric acid, bis-hydroiodic acid ester or, in particular, bis-bromohydric acid ester or hydrobromic hydrochloric acid ester. In addition, diesters of strong organic acids, e.g. sulfonic acids such as methanesulfonic acid, benzenesulfonic acid, p-chloro or p-bromo-benzenesulfonic acid or p-toluenesulfonic acid, can also be used. These diesters of the compounds of formula II are preferably reacted in a suitable inert solvent at a reaction temperature of 20-130 ° C. As the inert solvent, for example, hydrocarbons such as benzene or toluene, halogenated hydrocarbons such as chloroform, lower alcohols such as ethanol and especially methanol, ethereal liquids such as ether or dioxane, and lower alkanones, especially acetone, methyl ethyl ketone or the like can be used. benzene-methanol.

When one molar equivalent of the diester of diethanol of formula II is reacted with one molar equivalent of the free base of formula III, two molar equivalents of acid are cleaved, preferably bound to an acid scavenger. Alkali carbonates, such as potassium carbonate, e.g. alkali metal hydroxides, such as sodium hydroxide or potassium hydroxide, or an excess of a base of formula III, in addition to tertiary organic bases, such as pyridine and in particular triethylamine-ethyl-N-isopropyl or N-isethylamine, can be used as acid-binding agents. .

The starting materials used directly, i.e. the reactive diesters of formula II, can be prepared from diethanolols by esterification or replacement of the hydroxy groups with halogen according to conventional methods. Diethanolols, in turn, can be prepared from the corresponding methyl acetic acid esters by reduction with lithium aluminum hydride. Diacetic acid methyl esters can be prepared from the corresponding diacetonitriles with methanol and two molar equivalents of water by introducing hydrogen chloride into the mixture. Diacetonitriles, in turn, can be obtained from the corresponding bis- (bromomethyl) compounds with sodium cyanide.

According to another method, compounds of formula I having a group having the same meaning as the group R 1 alkanoyloxy lower alkyl are obtained by reducing a compound of formula * 1 ° 2 N \ / Ql

IV

A I | wherein at least one of the symbols and Q2 represents an oxygen atom, the other optionally 2 hydrogen atoms.

The reduction is preferably carried out with a complex hydride such as lithium aluminum hydride or diborane or aluminum hydride. The solvent used is preferably an ethereal liquid such as diethyl ether, tetrahydrofuran, dioxane, ethylene glycol dimethyl ether or diethylene glycol dimethyl ether. The reaction temperature is preferably about 0 to 100 ° C, or the boiling point of the reaction intermediate used. Diborane can be prepared either separately and introduced into the mixture, or formed in situ from sodium borohydride and boron trifluoride etherate. In addition, an activator such as aluminum chloride can be used for the reaction of lithium aluminum hydride.

The N-substituted lactam and imide compounds of the starting materials of formula IV can be prepared by substituting the corresponding non-N-substituted compounds of formula IV.

This N-substitution can be carried out by methods known per se, e.g. of the formula R 1 - with a reactive ester of the corresponding hydroxy compound according to OH, having the same meaning as above, with the exception of hydrogen.

Non-N-substituted imides of formula IV can be prepared from the corresponding diacetonitriles by forming an azepine ring with hydrogen bromide followed by treatment with water and dimethylformamide. From these imides, the corresponding lactams can be prepared by partial reduction with a complex hydride in an ethereal solvent such as diethyl ether or tetrahydrofuran.

After the reactions according to the invention, a number of further reactions can be carried out, if desired, by which the compounds of the formula I are converted into other compounds of the formula I.

If desired, a compound of formula I in which the residue R 1 represents hydrogen can be converted into a compound in which the residue R 1 represents something else.

Thus, for example, an N substitution can be performed on either the formula R * V-OH

IV

with the corresponding reactive ester of an alcohol in which R 1 is the same as R 1 in formula I, with the exception of hydrogen, or by reacting with the corresponding aldehydes or ketones under reducing conditions.

The reaction of compounds of formula I, wherein R 4 is hydrogen, with a reactive ester of a hydroxy compound of formula R-OH is preferably carried out in a solvent at a reaction temperature of 20 to 130 ° C, for example at the boiling point of the solvent.

As the reactive esters, e.g. halides, such as chlorides or bromides, in addition to sulfonic acid esters, such as o- or p-toluenesulfonic acid methyl esters, ethyl esters, or sulfuric acid esters, such as, for example, dimethyl or diethyl sulfate, can be used. Alkali metal carbonates, such as potassium carbonate, or alkali hydroxides, such as sodium hydroxide, or tertiary organic bases, such as e.g.

9,64582 pyridine or N-ethyldiisopropylamine. Suitable solvents are those which are inert under the reaction conditions, for example hydrocarbons, such as benzene or toluene, in addition to alkanols, such as, for example, methanol or ethanol, or alkanols, such as acetone or methyl ethyl ketone.

IV

Aldehydes and ketones corresponding to alcohols of the formula - OH are, for example, lower aliphatic aldehydes or ketones, lower free, esterified or etherified hydroxyoxoalkanes.

The reaction product obtained in the reaction of these aldehydes and ketones with said compounds of formula I can be reduced in the same step or afterwards.

Aldehydes, e.g. formaldehyde or acetaldehyde, or ketones, e.g. acetone, are reacted with, for example, said compounds of formula I in an inert solvent, to about 30-100 ° C and simultaneously and thereafter the reaction mixture is hydrogenated with hydrogen in the presence of a catalyst. Suitable solvents are, for example, alkanols, such as methanol or ethanol, and suitable catalysts are noble metal catalysts, such as palladium-carbon or alloy backbone catalysts, such as Raney nickel.

Instead of hydrogen, other reducing agents, e.g. formic acid, can also be used for the reductive alkylation in the presence of a catalyst. In the mold of this alternative procedure, said compounds of the formula I are heated in the soil with formic acid and aldehydes or ketones of said type, in particular formaldehyde, preferably without solvent.

However, the N-substitution with alkyl can also take place by first acylating the resulting compound in which the residue R1 represents hydrogen and then reducing the carbonyl group. This reduction is preferably performed with a complex hydride such as lithium aluminum hydride or diborane. As the solvent, an ethereal liquid such as diethyl ester, tetrahydrofuran, dioxane, ethylene glycol triethyl ether or diethylene glycol dimethyl ether is preferably used. The reaction temperature is preferably about 0 to 100 ° C, or is the boiling point of the reduction medium used. Diborane can be prepared either separately and derived from the reaction mixture, or also in situ from sodium borohydride and boron trifluoride etherate.

In addition, a compound of formula I in which the residue R 1 is a hydroxy-lower alkyl group may, if desired, be acylated to a compound in which the residue R 1 is an alkanoyloxy-lower alkyl group.

10 64582

The acylation can be carried out, for example, with a carboxylic acid anhydride or a corresponding carbonyl halide, at a reaction temperature of about 20 to 100 ° C. Since the condensation takes place while the acid is cleaved, it is expedient to add an acid-binding substance, e.g. a tertiary organic base, such as pyridine, to the reaction mixture. The additional tertiary organic base can also be used as a solvent. In addition, a hydrocarbon, e.g. benzene or toluene, or a halogenated hydrocarbon, e.g. chloroform, can be used as the solvent.

In addition, a compound of formula I in which the residue R 1 represents a phenyl-lower alkyl group may, if desired, be hydrogenated to a compound of formula I in which the residue represents hydrogen.

The hydrogenation may be carried out in the presence of conventional hydrogenation catalysts, for example noble metal catalysts such as palladium on carbon or platinum oxide, or rhodium catalysts such as rhodium carbon or rhodium alumina or alloy catalysts such as Raney nickel in an inert organic solvent such as Raney nickel. in dioxane, at room temperature and normal pressure or at a moderately elevated temperature up to about 100 ° C and / or at elevated pressure, up to about 100 bar.

In addition, a compound of formula I wherein X represents a divalent radical having the structure

OF

R 3 and wherein R 1 represents hydrogen are converted to another compound of formula I in which the residue R 1 represents lower alkyl.

This reaction is preferably carried out by reacting said process product with a reactive lower alkyl ester in the presence of solvents and basic condensing agents.

As the reactive ester, for example, halides such as chlorides or bromides can be used, in addition to sulfonic acid esters such as o- or p-toluenesulfonic acid methyl esters or ethyl ester, or sulfuric acid ester such as dimethyl or diethyl sulfate. Alkali metal alkanoates such as potassium tert-butylate or similar amides such as sodium amide or metal hydrides such as sodium or lithium hydride can be used as basic condensing agents.

64582

Suitable solvents are those which are inert under the reaction conditions, for example hydrocarbons, such as benzene or toluene, in addition to ether-like liquids, e.g. tetrahydrofuran, dioxane, ethylene glycol dimethyl ether, or amides, such as phosphoric acid-hexamethyltriamide triamide.

However, this reaction can also be carried out by first acylating the above compound and then reducing the carbonyl group.

This reduction is preferably carried out with the aid of a hydride. The hydride used is preferably diborane in an ethereal reaction medium such as tetrahydrofuran, dioxane, ethylene glycol dimethyl ether or diethylene glycol dimethyl ether. The reaction temperature is preferably -20 to + 80 ° C, more preferably between 0 and room temperature. The required diborane is prepared, for example, from boron trifluoride etherate and sodium borohydride either separately, e.g. in a solvent used for reduction, and used as a solution or formed in, for example, diethylene glycol dimethyl ether and introduced into the reaction mixture as a gas, or formed in situ.

Depending on the process conditions and starting materials, the final products are possibly obtained in free form or in the form of their salts, which can be converted into each other or into other salts in the usual way. Thus, the free compounds of formula I are formed from the acid addition salts obtained, e.g. by treatment with bases or basic ion exchangers, while the free bases of formula I are converted into acid addition salts, e.g. by reactions with organic or inorganic acids, especially to form.

Salts of the new compounds can also be used for purification purposes, e.g. by converting the free compounds to their salts, isolating these and possibly purifying them and converting them back to the free compounds. Since the new compounds in free form and in the form of their salts are very similar, in the above and in the following, the free compounds are to be understood simultaneously and expediently to mean the corresponding salts.

The invention also relates to those embodiments of the process which proceed from the intermediate compound at any stage of the process and perform the missing process steps or discontinue the process at any stage or form the starting material under reaction conditions or optionally use the reaction component in the form of a salt.

In order to carry out the process according to the invention, it is expedient to use such starting materials from which the groups of end products specifically mentioned at the beginning and in particular the end products described or preferred are obtained.

The novel compounds can be used, for example, in the form of pharmaceutical preparations containing an effective amount of the active ingredient, optionally together with inorganic or organic, solid or liquid, pharmaceutically acceptable carriers suitable for enteral, e.g. oral or parenteral, administration. Thus tablets or gelatin capsules are used which contain the active ingredient together with diluents, e.g. lactose, dextrose, sucrose, mannitol, sorbitol, cellulose and / or glycine and lubricating agents, e.g. diatomaceous earth, talc, steric acid or its salts, such as magnesium or calcium. with stearate and / or polyethylene glycol; tablets also contain binders, e.g. magnesium aluminum silicate, starches such as corn, wheat, rice or arrowroot starch, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and / or polyvinylpyrrolidone, and, if desired, disintegrant, such as sodium alginate and / or effervescent mixtures or an adsorbent, a colorant, a flavor and a sweetener. The novel pharmacologically active compounds can also be used in the form of injectable preparations, e.g. intravenously injectable preparations or infusion solutions. Such solutions are preferably isotonic, aqueous solutions or suspensions, which are prepared before use, e.g. from lyophilized preparations containing the active ingredient alone or in combination with a carrier, e.g. mannitol. The pharmaceutical preparations can be sterilized and / or contain auxiliaries, e.g. preservatives, stabilizers, wetting and / or emulsifiers, solubilizers, salts for regulating the osmotic pressure and / or buffers. These pharmaceutical preparations may, if desired, contain other pharmacologically valuable substances and are prepared in a manner known per se, e.g. by conventional mixing, granulating, granulating, dissolving or lyophilizing methods, and contain from about 0.1 to 100%, in particular from about 1 to about 50 %, and lyophilizates up to 100% of active ingredient. The dosage depends on the mode of use, the species, the age and the individual condition. The daily doses of the free bases or their pharmaceutically acceptable salts are about 0.1 to 10 mg / kg for warm-blooded patients in general, and about 0.01 g to about 0.5 g for warm-blooded animals weighing about 70 kg.

The following examples illustrate the invention; temperatures are given in degrees Celsius.

. A) 3-Ethyl-1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) -Example 1: cyclohepta (1,2-d) azepine

To a solution of 21.8 g (0.05 mol) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5H-dibenzo (a, d) cycloheptene in 200 ml of abs. ethanol, 35 ml (2.6 g; 0.06 mol) of a 7.4% solution of ethanol in ethylamine and 15.5 g (0.125 mol) of diisopropylethylamine are added and the reaction mixture is refluxed for 18 hours.

The reaction mixture is then evaporated in a water-jet vacuum, the residue is dissolved in 300 ml of methylene chloride and this solution is washed successively with 100 ml of 2N sodium hydroxide and water each time. The methylene chloride solution is evaporated in a water-jet vacuum to about 50 ml and 15 ml of 4N ethereal hydrogen chloride solution are added to give 3-ethyl-1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (l , 2-d) azepine hydrochloride, m.p. 296-200 °, crystallizes.

? 2H5 γ "νί

Melting point of methanesulfonate: 220-221 °.

The starting material can be prepared as follows from Example 5: 27 g (0.1 mol) of 5H-dibenzo (a, d) cycloheptene-10,11-diacetonitrile, 400 ml of methanol, 3.8 ml of water and dry clo-obtained. .

hydrogen / 5H-dibenzo [a, dicycloheptene-10,11-diacetic acid dimethyl ester, m.p. 104-106 ° (from hexane); 33.6 g (0.1 mol) of 5H-dibenzo (a, d) cycloheptene-10,11-diacetic acid dimethyl ester and 7.6 g (0.2 mol) of lithium aluminum are obtained,.

hydride in 1 liter of absolute diethyl ether / 5H-dibenzo [a, d] -cycloheptene-10,11-diethanol, m.p. 154-156 ° (from acetone).

To a solution of 28.0 g (0.10 moles) of 5H-dibenzo (a, d) cycloheptene-10,11-diethanol in 120 ml of pyridine is added dropwise at a reaction temperature of 14,64582 -5 ° 16.8 ml ( 25.2 g, 0.22 mol) of methanesulfonic acid chloride. It is then stirred for 30 minutes at 0 ° and then for 1 hour at 15-25 °. The reaction mixture is shaken with 600 ml of methylene chloride in a separatory funnel successively with 400 ml of 5N hydrochloric acid and ice water each time. The methylene chloride solution is separated, dried over magnesium sulfate and evaporated in a water-jet vacuum. The residue is 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5H-1-dibenzo (a, d) cycloheptene as a colorless thick-flowing oil.

In a similar manner can be prepared: B) 3-methyl-1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) -azepine methanesulfonate, m.p. p. 189-191 °, starting from 21.8 g (0.05 mol) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5H-dibenzo (a, d) cycloheptane, 30 ml (1.9 g; 0.06 mol) from 63% ethanolic methylamine solution and 15.5 g (0.125 mol) of diisopropylethylamine.

C) 3-Benzyl-1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine hydrochloride, m.p. 265-270 °, starting from 21.8 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5H-dibenzo (a, d) cycloheptene, from 6.2 g (0.06 moles) benzylamine and 15.5 g (0.125 moles) diisopropylethylamine.

Example 2: 1 / 2'3'4 · 5,1O-hexahydro-dibenzo (3,4: 6,7) cyclohepta - '(1,2-d) azepine

Suspension of 19.4 g (0.05 mol) of 3-benzyl-1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine hydrochloride and 2 g of 5% palladium on carbon in 900 ml of methanol are hydrogenated at normal pressure and 40-50 ° until 770 ml of hydrogen have been absorbed.

The catalyst is then sucked off and the filtrate is evaporated in a water-jet vacuum.

The remaining crude 1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine hydrochloride of the residue is recrystallized from ethanol, m.p. 295-300 °.

To liberate the base, the hydrochloride is suspended in 250 ml of methylene chloride and shaken with 100 ml of concentrated ammonia solution. The methylene chloride solution is separated and evaporated until crystallization begins. Hexane is then added, whereupon 1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine crystallizes, m.p. 190-191 °.

To convert it to the methanesulfonate, the free base is dissolved in methylene chloride, a theoretical amount of methanesulfonic acid and 1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) -! the azepine methanesulfonate is mixed with ether, m.p. 269-271 °.

15 64582 3- (Cyclopentylmethyl) -1,2,3,4,5,1O-hexahydro-di-Example 3: Benzo (3,4: 6,7) cyclohepta [1,2-d] azepine

To a solution of 43.6 g (0.1 mol) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5H-dibenzo (a, d) cycloheptane in 400 ml of absolute ethanol is added 11 .9 g (0.12 mol) of (aminomethyl) -cyclopentane and 32.3 g (0.25 mol) of diisopropylethylamine and the reaction mixture are refluxed for 20 hours. The reaction mixture is then evaporated in a water-jet vacuum, the residue is dissolved in 150 ml of methylene chloride and 500 ml of pentane and this solution is washed successively with 200 ml of 2N sodium hydroxide and water each time. 200 ml of 2N hydrochloric acid are then added to the organic phase, whereupon the hydrochloride separates as a granule. The crystals are filtered off with suction and the hydrochloride is suspended in 300 ml of methylene chloride and the mixture is shaken with 100 ml of concentrated ammonia solution. The methylene chloride solution is separated and evaporated until crystallization begins. Hexane is then added to give 3- (cyclopentylmethyl) -1,2,3,4,5,10-hexahydro-dibenzo (3,4-6,7) cyclohepta- (1,2-d) azepine, m.p. . 141-142 °, crystallizes. To convert it to methanesulfonate, the base is dissolved in methylene chloride, a theoretical amount of methanesulfonic acid is added and 3- (cyclopentyl-methyl) -1,2,3,4,5,10-hexahydro-dibenzo (3,4; 6,7) cyclohepta (1 , 2-d) - azepine methanesulfonate with ether, m.p. 248-249 °.

. 3-methyl-l, 2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) -

Example 4: glyphiohepta (1,2-d) azepine 26 to 1 g (0.1 mol) of 1,2,3,4,5,10-hexahydro-dibenzo (3,4; 6,7) cyclohepta ( 1,2-d) Azepine (prepared according to Example 2) is added under the same ice-cooling 92 g (2 moles) of formic acid and 20 g (0.2 moles) of 30% formaldehyde and stirred for 1 hour at 95-100 °. It is then poured into ice water and made alkaline with 10η sodium hydroxide. The separated base is dissolved in methylene chloride and the methylene chloride solution is evaporated until crystallization begins. Hexane is then added to crystallize 3-methyl-1,2,3,4,5,10-hexahydro-dibenzo (3,4; 6,7) cyclohepta (1,2-d) azepine, m.p. 144-146 °. To convert the base to the methanesulfonate, it is dissolved in methylene chloride, a theoretical amount of methanesulfonic acid and 3-methyl-1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine methanesulfonate are added. precipitated with ether, m.p. 189-191 °.

'6 64582 3-Benzyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -Example 5: thiepino (4,5-d) azepine

To a solution of 4.56 g (0.01 mol) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) thiepine in 50 ml of absolute ethanol is added 1.3 g (0.012 mol) of benzylamine and 3.25 g (0.025 mol) of diisopropylethylamine and the reaction mixture are refluxed for 18 hours. After cooling, crystals separate in the ice bath, which are sucked off and washed with a small amount of isopropanol and pentane. The filtrate is 3-benzyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) -azepine, m.p. 149-150 °.

i

V

CH, a ^

To convert the base to the hydrochloride, 3.0 g of base are dissolved in 100 ml of acetone and 2.2 ml of a 4N solution of hydrogen chloride in ether and enough ether are added with stirring until the solution becomes slightly cloudy. 3-Benzyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine hydrochloride is allowed to crystallize, m.p. 241-242 °.

The starting material can be prepared as follows: 58 g (0.2 mol) of dibenzo (b, f) thiepine-10,11-diacetonitrile are suspended with stirring in 800 ml of methanol and 7.5 ml of water and cooled in an ice bath to 0-5 °. C. Dry hydrogen chloride is then introduced within one hour to form a clear solution. The temperature is maintained at 5-20 ° during the addition. The reaction mixture is then further stirred for 1 hour at room temperature, then for 4 hours while refluxing and then completely evaporated to dryness on a rotary evaporator. The residue is dissolved in ether, the ether solution is washed with water and 2N sodium hydroxide solution and, after drying over sodium sulphate, it is evaporated off completely.

17 64582 The oily residue is dissolved in methanol and cooled to 0 °, whereby dibenzo (b, f) thiepine-10,11-diacetic acid methyl ester crystallizes, which, after suction filtration and drying at 50 ° under reduced pressure, melts at 84-86 °.

To a suspension of 7.6 g (0.2 moles) of lithium aluminum hydride in 400 ml of absolute diethyl ether is added dropwise, with stirring and protection from moisture and under a nitrogen atmosphere, within one hour, a solution of 35.4 g (0.1 moles) of dibenzo (b, f) thiepine-10,11-diacetic acid dimethyl ester in 1 liter of absolute diethyl ether and then the reaction mixture is refluxed for 6 hours under reflux. After cooling, 130 ml of water are added dropwise to the 0-5 ° reaction mixture, followed by separation of the organic phase; washed with water and, after drying, evaporated over sodium sulfate to a small volume to give dibenzo (b, f) thiepine-10,11-diethanol, m.p. 131-133 °, crystallizes.

15 g (0.5 mol) of dibenzo (b, f) thiepine-10,11-diethanol are dissolved in 60 ml of pyridine at room temperature and, while stirring in an ice-sodium chloride bath, 8.4 ml (12 ml) are added dropwise at a reaction temperature of -5 °. , 6 g; 0.11 moles) of methanesulfonic acid chloride. The reaction mixture is then stirred for 30 minutes at 0 ° and then for 1 hour at 15-25 °. It is then shaken together with 500 ml of methylene chloride in a separatory funnel successively with 400 ml of 2N hydrochloric acid and water each time. The methylene chloride solution is separated, dried over magnesium sulfate and evaporated in a water-jet vacuum. The residue gives 10,11-bis- (2- (methylsulphonyloxy) ethyl) dibenzo (b, f) thiepine, m.p. 107-108 °.

Example 6: 3- (2-Phenylethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine

According to Example 5, the following can be prepared: from 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo b, f-thiepine, from 7.3 g (0.06 moles) of 2-phenylethylamine and 16.25 g (0.125 moles) of diisopropylethylamine in absolute ethanol 3- (2-phenylethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2 , 3: 6,7) thiepino (4,5-d) azepine, m.p. 96-99 ° (from acetonitrile); methanesulfonate m.p. 161-164 ° (from absolute ethanol).

Example 7: 7-Methoxy-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7) thiepino (4,5-d) azepine

According to Example 5, the following can be prepared: 64582 18 24.2 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-methoxy-dibenzo (b, f) thiepine, 1.85 g (0.06 mol) of methylamine and 16.25 g (0.125 mol) of diisopropylethylamine in absolute ethanol 7-methoxy-3-methyl-2,3,4,5-tetrahydro-1H -dibenzo (2,3: 6,7) thiepino (4,5-d) azepine, m.p. 108-112 ° (from acetone); hydrochloride m.p. 220-224 ° (abs. Ethanol).

The starting material can be prepared as follows: from 42.3 g (0.1 moles) of 2-methoxy-10,11-bis- (bromomethyl) dibenzo (b, f) thiepine and from 11.8 g (0.24 moles) sodium cyanide in 500 ml of acetonitrile 2-methoxy-dibenzo (b, f) thiepine-10,11-diacetonitrile, m.p. 198-200 ° (from acetonitrile); 31.8 g (0.1 mol) of 2-methoxy-dibenzo (b, f) thiepine-10,11-diacetonitrile, 400 ml of methanol, 3.8 ml of water and dry hydrogen chloride 2-methoxy-dibenzo (b, f) thiepine-10,11-diethylacid-ρο-dimethyl ester, m.p. 96-98 ° (from toluene); 38.5 g (0.1 mol) of 2-methoxy-dibenzo (b, f) thiepine-10,11-diacetic acid dimethyl ester and 7.6 g (0.2 mol) of lithium aluminum hydride per liter of abs . diethyl ether 2-methoxy-dibenzo (b, f) thiepine-10,11-diethanol, m.p. 116-119 ° (from ethyl acetate / hexane); 32.8 g (0.2 mol) of 2-methoxy-dibenzo (b, f) thiepine-10,11-diethanol, 25.2 g (0.22 mol) of methanesulphonic acid chloride in 120 ml of pyridine 10.11- bis- (2- (methylsulfonyloxy) -ethyl) -2-methoxy-dibenzo (b, f) thiepine, crude product.

Example 8: 7-Methylthio-3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine

According to Example 5, 25.0 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-methylthio-dibenzo (b, f) thiepine, 6.0 g can be prepared. (0.06 moles) of (aminomethyl) cyclopentane and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 7-methylthio-3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) -azepine, crude; methanesulfonate m.p. 206-209 ° (abs. From ethanol).

The starting material can be prepared as follows: from 44.2 g (0.1 mol) of 2-methylthio-10,11-bis- (bromomethyl) dibenzo (b, f) thiepine and from 11.8 g (0.24 mol) moles) of sodium cyanide in 500 ml of acetonitrile 2-methylthio-dibenzo (b, f) thiepine-10,11-19} 64582 diacetonitrile, m.p. 204-206 ° (from ethyl acetate); 33.4 g (0.1 mol) of 2-methylthio-dibenzo (b, f) thiepine-10.11-diacetonitrile, 400 ml of methanol, 3.8 ml of water and dry hydrogen chloride 2-methylthio-dibenzo (b, f) thiepine-10,11-diethyl acid dimethyl ester, m.p. 85-86 ° (from pentane); 40.0 g (0.1 mol) of 2-methylthio-dibenzo (b, f) thiepine-10.11-diacetic acid dimethyl ester and 7.6 g (0.2 mol) of lithium aluminum hydride in 1 liter of absolute diethyl ether 2-methylthio -dibenzo (b, f) thiepine-10,11-diethanol, m.p. 58-60 ° (from diethyl ether); 34.5 g (0.1 mol) of 2-methylthio-dibenzo (b, f) thiepine-10.11-diethanol, 25.2 g (0.22 mol) of methanesulphonic acid chloride in 120 ml of pyridine 10.11- bis- (2- (methylsulfonyloxy) ethyl) -2-methylthio-dibenzo (b, f) thiepine, crude product.

Example 9: 3,7-Dimethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine

According to Example 5, the following can be prepared: from 23.4 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-methyl-dibenzo (b, f) thiepine, 1.85 g (0.06 moles) of methylamine and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 3,7-dimethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine, crude; hydrochloride m.p. 265-268 ° (abs. From ethanol).

The starting material can be prepared as follows: from 41.0 g (0.1 mol) of 2-methyl-10,11-bis- (bromomethyl) -dibenzo (b, f) thiepine and 11.8 g (0.24 mol) sodium cyanide in 500 ml of acetonitrile 2-methyl-dibenzo (b, f) thiepine-10,11-diacetonitrile, m.p. 198-200 ° (from acetonitrile)? 30.2 g (0.1 mol) of 2-methyl-dibenzo (b, f) thiepine-10,11-diacetonitrile, 400 ml of methanol, 3.8 ml of water and dry hydrogen chloride 2-methyl-dibenzo ( b, f) thiepine-10,11-diethyl acid dimethyl ester, m.p. 76-77 ° (from methanol); 36.9 g (0.1 mol) of 2-methyl-dibenzo (b, f) thiepine-10,11-diacetic acid dimethyl ester and 7.6 g (0.2 mol) of lithium aluminum hydride per liter of absolute diethyl ether 2-methyl-dibenzo (b, f) thiepine-10,11-diethanol, m.p. 126-129 ° (from acetonitrile); 31.2 g (0.01 mol) of 2-methyl-dibenzo (b, f) thiepine-20 64 5 82 10,11-diethanol, 25.2 g (0.22 mol) of methanesulphloride in 120 ml of pyridine 10,11-Bis- (2- (methylsulfonyloxy) -ethyl) -2-methyl-dibenzo (b, f) thiepine, crude product.

Example 10: 7-Bromo-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7) thiepino (4,5-d) azepine

According to Example 5, 26.7 g (0.05 mol) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-bromo-dibenzo (b, f) thiepine can be prepared from 1.85 g (0.06 moles) methylamine and 16.25 g (0.125 moles) diisopropylethylamine abs. in ethanol 7-bromo-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine, crude; hydrochloride din sul.p. 280 ° (decomposes) (abs. From ethanol).

The starting material can be prepared as follows: from 47.5 g (0.1 mol) of 2-bromo-10,11-bis- (bromomethyl) -di-benzo (b, f) thiepine and 11.8 g (0 , 24 moles) of sodium cyanide in 500 ml of acetonitrile 2-bromo-dibenzo (b, f) thiepine-10,11-di-acetonitrile, m.p. 200-204 ° (from acetonitrile); 36.7 g (0.1 mol) of 2-bromo-dibenzo (b, f) thiepine-10,11-diacetonitrile, 400 ml of methanol, 3.8 ml of water and dry hydrogen chloride 2-bromo-dibenzo ( b, f) thiepine-10,11-diacetic acid dimethyl ester, m.p. 90-93 ° (abs. Ethanol); 43.4 g (0.1 mol) of 2-bromo-dibenzo (b, f) thiepine-10,11-diacetic acid dimethyl ester and 7.6 g (0.2 mol) of lithium aluminum hydride per liter of abs . diethyl ether 2-bromo-dibenzo- (b, f) thiepine-10,11-diethanol, m.p. 166-169 ° (from diethyl ether); 37.7 g (0.1 mol) of 2-bromo-dibenzo (b, f) thiepine-10,11-diethanol and 25.2 g (0.22 mol) of methanesulphonic acid chloride in 120 ml of pyridine 10.11- bis- (2- (methylsulfonyloxy) -ethyl) -2-bromo-dibenzo (b, f) thiepine, m.p. 94-96 ° (from benzene ether).

21 64582

Example 11: 3-Methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -oxepino (4,5-d) azepine

According to Example 5, 21.9 g (0.05 mol) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) oxepine can be prepared from 1.85 g (0 .06 moles) of methylamine and 16.25 g (0.125 moles) of diisopropylethylamine 3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) oxepino (4,5-d) -azepine, m.p. 147-149 ° (from acetonitrile); hydrochloride m.p. 282-285 ° (abs. From ethanol); The starting material can be prepared as follows: from 38 g (0.1 mol) of 10,11-bis- (bromomethyl) dibenzo (b, f) -oxepine and from 11.8 g (0.24 mol) ) sodium cyanide in 500 ml acetonitrile dibenzo (b, f) oxepine-10,11-diacetonitrile, m.p. 176-178 ° (from methanol); 27.2 g (0.1 mol) of dibenzo (b, f) oxepine-10,11-diacetonitrile, 400 ml of methanol, 3.8 ml of water and dry hydrogen chloride dibenzo (b, f) oxepine 10,11-Diacetic acid dimethyl ester, m.p. 65-67 ° (from pentane); 33.8 g (0.1 mol) of dibenzo (b, f) oxepine-10,11-diethylacetic acid dimethyl ester and 7.6 g (0.2 mol) of lithium aluminum hydride per liter of abs. diethyl ether dibenzo (b, f) oxepine-10,11-diethanol, m.p. 138-140 ° (from acetone); 28.2 g of dibenzo (b, f) oxepine-10,11-diethanol and 25.2 g (0.22 mol) of methanesulphonic acid chloride in 120 ml of pyridine 10,11-bis- (2- (methylsulfonyloxy)) -ethyl) dibenzo (b, f) oxepine, m.p. 112-114 ° (from methylene chloride).

Example 12: 3-Isopropyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -oxepino (4,5-d) azepine

According to Example 5, the following can be prepared: 22,64582 from 21.9 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) oxepine, from 3.5 g (0 .06 moles) of isopropylamine and 16.25 g (0.125 moles) of diisopropylethylamine 3-isopropyl-2,3,4,5-tetrahydro-1H-dibenzo (2.3: 6.7 ) oxepino- (4,5-d) azepine, m.p. 125-128 ° (from acetonitrile); maleate sul.p. 175-177 ° (from acetone).

Example 13: 3-Methyl-10-ethyl-1,2,3,4,5,10-hexahydro-dibenzo- (b, f) azepino (4,5-d) azepine

According to Example 5, the following can be prepared: from 23.3 g (0.05 moles) of 10-11, bis- (2- (methylsulfonyloxy) ethyl) -5-ethyl-5H-dibenzo (b, f) azepine, 1.85 g (0.006 moles) methylamine and 16.25 g (0.125 moles) diisopropylethylamine 3-methyl-10-ethyl-1,2,3,4,5,10-hexahydro-dibenzo- (b, f) azepine (4,5-d) azepine, m.p. 99-100 ° (from toluene); branched sul.p. 180-183 ° (abs. Ethanol); CH

I J

m = 2H5 The starting material can be prepared as follows: from 42.1 g (0.1 mol) of 5-acetyl-10,11-bis- (bromomethyl) -5H-dibenzo (b, f) azepine and 11.8 g: (0.24 mol) of sodium cyanide in 500 ml of acetonitrile 5-acetyl-5H-dibenzo (b, f) azepine-10,11-diacetonitrile, m.p. 183-184 ° (from benzene); 31.3 g (0.1 mol) of 5-acetyl-5H-dibenzo (b, f) azepine-10.11-diacetonitrile, 400 ml of methanol, 3.8 ml of water and dry hydrogen chloride 5-acetyl-5H- dibenzo (b, f) azepine-10,11-diacetic acid dimethyl ester, m.p. 123-124 ° (from toluene); 37.9 g (0.1 mol) of 5-acetyl-5H-dibenzo (b, f) azepine-10.11-diacetic acid dimethyl ester and 7.6 g of lithium aluminum hydride in 150 ml of abs. tetrahydrofuran 5-ethyl-5H-dibenzo- (b, f) azepine-10,11-diethanol, m.p. 102-105 ° (from ether); 23 6 4 5 8 2 30.9 g (0.1 mol) of 5-ethyl-5H-dibenzo (b, f) azepine-10.11-diethanol and 25.2 g (0.22 mol) of methanesulphonic acid chloride 120 in ml of pyridine 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5-ethyl-5H-dibenzo (b, f) azepine, m.p. 140-143 ° (from to-lene).

Example 14: 3-Allyl-10-ethyl-1,2,3,4,5,10-hexahydro-dibenzo- (b, f) azepino (4,5-d) azepine

According to Example 5, the following can be prepared: from 23.3 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5-ethyl-5H-dibenzo (b, f) azepine, 3, 4 g (0.06 mol) of allylamine and 16.25 g (0.125 mol) of diisopropylethylamine 3-allyl-10-ethyl-1,2,3,4,5,10-hexahydro -dibenzo (b, f) -azepino (4,5-d) azepine, m.p. 100-101 ° (from hexane); hydrochloride sul.p. 245-248 ° (abs. From ethanol / acetone).

Example 15: 3-Methyl-1,2,3,4,5,10-hexahydro-dibenzo (b, f) azepino (4,5-d) azepine

According to Example 5, 21.9 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5H-dibenzo (b, f) azepine can be prepared from 1.85 g (0 .06 moles) methylamine and 16.25 g (0.125 moles) of diisopropylethylamine 3-methyl-1,2,3,4,5,10-hexahydro-dibenzo (b, f) azepino (4,5-d) -azepine, m.p. 121-124 ° (from methanol); methanesulfonate m.p. 263-266 ° (abs. From ethanol / acetone).

The starting material can be prepared as follows: from 37.9 g (0.1 mol) of 5-acetyl-5H-dibenzo (b, f) azepine-10.11-diacetic acid dimethyl ester and 7.6 g of lithium aluminum hydride per liter of abs. diethyl ether 5H-dibenzo (b, f) azepine-10,11-diethanol, m.p. 180-182 ° (from acetone); 28.1 g (0.1 mol) of 5H-dibenzo (b, f) azepine-10,11-diethanol and 25.2 g (0.22 mol) of methanesulphonic acid chloride in 120 ml of pyridine 10.11- bis- (2- (methylsulfonyloxy) ethyl) -5H-dibenzo (b, f) azepine m.p. 140-142 ° (from toluene).

Example 16: 3- (Cyclopentylmethyl) -1,2,3,4,5,10-hexahydro-dibenzo (b, f) azepino [4,5-d] azepine

According to Example 5, 21.9 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5H-dibenzo (b, f) azepine can be prepared from 6.0 g (0 .06 moles) of (aminomethyl) -cyclopentane and 16.25 g (0.125 moles) of diisopropyl-24 6 4 5 8 2 li-ethylamine 3- (cyclopentylmethyl) -1,2,3,4,5 , 10-hexahydro-dibenzo (b, f) azepino (4,5-d) azepine, m.p. 72-75 ° (from pentane); methanesulfonate m.p. 271-274 ° (from methanol).

Example 17: 7-Hydroxy-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7) -thiepino (4,5-d) azepine

A mixture of 16.2 g (0.05 mol) of 7-methoxy-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine ( prepared according to Example 7) and 40 ml of 48% aqueous hydrobromic acid, refluxed for 2 hours with stirring and then cooled to 20 °. The precipitated hydrobromide of 7-hydroxy-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine is filtered off and dissolved in 160 ml of 60% aqueous methanol. The solution is made phenophthalein alkaline by adding a concentrated aqueous ammonia solution to give the free 7-hydroxy-3-64582 methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5- d) my azepine crystallizes. After recrystallization, the product melts at 216-218 ° from acetonitrile.

To convert the base to the methanesulfonate, 9.3 g (0.03 moles) of the base are dissolved in 380 ml of acetone and 2.8 g (0.03 moles) of methanesulfonic acid are added to the solution with stirring, whereby 7-hydroxy-3-methyl-2,3, 4,5-Tetrahydro-1H-dibenzo (2,3: 6,7) thiepino- (4,5-d) azepine methanesulfonate crystallizes, m.p. 282-286 °.

_. . 10-Cyano-3-methyl-2,3,4,5-tetrahydro-1F-dibenzoic acid

Example 18 = (2> 3.6 j7) tiepii0 (4,5-d) azepine

A mixture of 18.6 g (0.05 mol) of 7-bromo-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5- d) azepine (prepared according to Example 10) and 10.7 g (0.12 mol) of copper I-cyanide in 20 ml of dimethylformamide are heated under nitrogen for 22 hours with stirring to 180 °. It is then cooled to 30 [deg.] C., diluted with 100 ml of methylene chloride and treated with 50 ml of 50% aqueous ethylenediamine solution. The organic phase is then dissolved, washed with water and, after drying, evaporated over sodium sulfate. The crystalline residue, 7-cyano-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine, melts after recrystallization from hexane / acetic acid ethyl ester. at 154-157 °.

To convert the base to methanesulfate, 9.6 g (0.03 moles) of base are dissolved in 50 ml of acetone, and 2.88 g (0.03 moles) of methanesulfonic acid are added to this solution with stirring under Saimaa to give 7-cyano-3-methyl-2,3 , 4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) -azepine methanesulfonate crystallizes, m.p. 247-250 °.

3- (3-Octanoyloxypropyl) -2,3,4,5-tetrahydro-1H-Example 19: dibenzo (2,3: 6,7) thiepino (4,5-d) azepine

To a solution of 16.9 g (0.05 moles) of 2,3,4,5-tetrahydro-1H-β, (prepared according to Example 32) dibenzo (2,3: 6,7) , 5-d Jazepine-3-propanol / 50 ml abs.

pyridine, 12.2 g (0.07 mol) of octanoyl chloride are added over 15 minutes with stirring, keeping the temperature between 0 and 5 °. It is then stirred for a further 20 hours at room temperature. The reaction mixture is then poured into ice water and extracted with ether. The organic phase is separated, washed with water and, after drying over sodium sulphate, evaporated to dryness to give 3- (3-octanoyloxypropyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) as an oily residue. ) thiepino (4,5-d) azepine.

21.5 g of crude base are dissolved in 150 ml of acetone and a solution of 4.2 g (0.047 mol) of anhydrous oxalic acid 26 64582 in 22 ml of abs. alcohol, whereby 3- (3-octanoyloxypropyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine oxalate crystallizes, which after recrystallization ethanol melts at 157-162 °.

In the same way can be prepared. silicon B) 3- (3-Acetoxypropyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) acetone / 16.9 g: of (0.05 mol) 2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine-3-propanol in 50 ml of abs. pyridine and 5.9 g (0.075 mol) of acetyl chloride 3- (3-ethoxypropyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) Melting point of the oxalate 156-160 ° (from ethanol).

is 3-ethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino-Example (4,5-d) azepine in 75 ml of a 7.4% solution of ethylamino abs . in ethanol (corresponding to 0.012 mol), 3.25 g (0.025 mol) of diisopropylethylamine, 50 ml of abs. ethanol and 4.5 g (0.01 mol) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) thiepine (prepared according to Example 5) and the mixture is heated in a sealed tube for 20 hours 85-90 ° C. After cooling, the reaction mixture is rinsed with 250 ml of methylene chloride into a separatory funnel and shaken successively with 50 ml of 2N sodium hydroxide and water each time. The methylene chloride solution is evaporated in a water-jet vacuum and the crude 3-ethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine is converted into the hydrochloride as follows: 3.1 g of residue, which is a brown viscous oil, is dissolved in 25 ml of methylene chloride and 3 ml of 4N ethereal hydrogen chloride solution are added. 3-Ethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine hydrochloride is mixed with ether, filtered off with suction and recrystallized from m.p. 271 °, decomposed once from ethanol-ether; / melting point of methanesulronate 212-

Ai jO

3-Methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) road Example 21: stack (4,5-d) azepine

To a suspension of 14.6 g (0.38 moles) of lithium aluminum hydride in 1 liter of absolute diethyl ether is added, under stirring under a nitrogen atmosphere, a suspension of 32.1 g (0.1 moles) of 3-methyl-1 over 20 minutes. 5-Dihydro-2H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine-2,4 (3H) -dione in 500 ml of abs. diethyl ether, keeping the temperature at 20-30 °. The reaction mixture is then refluxed for a further 15 hours and then cooled to 0-5 °. Carefully add 75 ml of acetic acid diethyl ester dropwise, followed by 150 ml of water to decompose the excess lithium aluminum hydride. The organic phase is then separated and extracted several times with 5% methanesulfonic acid. The acidic extracts are made alkali with phenolphthalein with concentrated ammonia, whereby the crude 3-methyl-2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7) thiepino (4,5-d) azepine separates as an oil. The crude base is extracted with ether, the organic phase is separated off, washed with water and, after complete drying, evaporated over sodium sulphate. The residue is dissolved in 50 ml of petroleum ether and cooled to 0 °, whereupon a pure base with a melting point of 83-86 ° crystallizes. Melting point of methanesulfonate: 256-258 °.

The starting material, 3-methyl-1,5-dihydro-2H-dibenzo (2,3: 6,7) thiepino- (4,5-d) azepine-2,4 (3H) -dione, can be prepared as follows:

To a solution of 30.7 g (0.1 mol) of 1,5-dihydro-2H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine-2,4 (3H) dione (prepared according to Example 22) and 16.6 g (0.12 mol) of methyl iodide in 1 liter of methylene chloride are added with stirring under a nitrogen atmosphere over 30 minutes a solution of 28.5 g (0.11 mol) of tetrabutylammonium hydroxide in 45 ml: in water, increasing the temperature from 20 to 25 °. The reaction mixture is then stirred for a further 5 hours at room temperature and then 250 ml of water are added. The organic phase is separated, washed with water and, after drying over sodium sulphate, evaporated to dryness. The crystalline residue is stirred with 50 ml of abs. ethanol, filtered off with suction and washed with absolute ethanol. The product, 3-methyl-1,5-dihydro-2H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine-2,4 (3H) -dione, melts after drying 216- 222 ° C.

Example 22 · 2'3 · 4 · 5-Tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) - 'azepine In an ice-cooled solution of 4 g (0.03 mol) ) aluminum chloride in 100 ml of abs. diethyl ether, a suspension of 1.14 g (0.03 moles) of lithium aluminum hydride in 75 ml of abs is slowly added under stirring under a nitrogen atmosphere with stirring and protection from moisture. diethyl ether so that the reaction temperature does not exceed 5 °. A suspension of 2.93 g (0.01 mol) of 1,3,4,5-tetrahydro-2H-dibenzo (2,3: 6,7) thiepino 4,5-d-azepine-2-ol onia in 50 ml abs. diethyl ether and the mixture is refluxed for 24 hours. After cooling to 0-5 °, the excess aluminum hydride is decomposed by careful dropwise addition of 10 ml of water. The organic phase is then separated, washed twice with 30 ml of water each time, dried over sodium sulphate and evaporated. The residue is 2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) to 28,64582 thiepino (4,5-d) azepine which, after recrystallization, melts at 142-143 ° of methanol. . Melting point of methanesulfonate 305-307 °.

The starting material, 1,3,4,5-tetrahydro-2H-dibenzo (2,3: 6,7) thiepino (4,5-d) -azepin-2-one, can be prepared as follows: 198 g) 0.5 moles) 10,11-bis- (bromomethyl) -dibenzo (b, f) thienine is dissolved in 2.5 liters of acetonitrile under a nitrogen atom at 50 ° with stirring. To this solution is added dropwise within 10 minutes a solution of 59 g of sodium cyanide in 180 ml of distilled water, maintaining the internal temperature while cooling to 50 °. The reaction mixture is then stirred for a further 30 minutes at this temperature and then poured into 1.5 liters of ice water, whereby dibenzo (b, f) thiepine-10,11-diacetonitrile crystallizes. The gray crystals are filtered off with suction, washed with water and then with acetonitrile and finally dried in vacuo at 60 °, m.p. 205-207 °.

145 g (0.05 mol) of dibenzo (b, f) thiepine-10,11-diacetonitrile are dissolved in 2.75 ml of methylene chloride while stirring. Dry hydrogen bromide is introduced into this solution under ice-cooling at 5-7 ° for 30 minutes, after which time yellow crystals separate from the reaction mixture. The addition of hydrogen bromide is then stopped and stirred for another 30 minutes at 5-7 °. The reaction mixture is then distilled off about half of the solvent in vacuo, the remaining crystalline porridge is filtered off with suction, washed thoroughly with methylene chloride and the slightly yellowish crystals are dried under reduced pressure at 60 °. The 2-amino-4-bromo-1H-dibenzo- (2,3: 6,7) thiepino (4,5-d) azepine hydrobromide thus obtained is further treated as a crude product.

To 90 g (0.2 moles) of 2-amino-4-bromo-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine hydrobromide, 1.5 liters of dimethylformamide and 1 .3 liters of water are boiled while stirring under a nitrogen atmosphere for 2 hours at reflux. The reaction mixture is then diluted at 90-100 ° with 800 ml of water and then cooled with ice to 5 ° to give 1,5-dihydro-2H-dibenzo (2,3: 6,7) thiepino (4,5-d ) azepine-2,4 (3H) -dione crystallizes, which is filtered off with suction and washed thoroughly with water and acetone. After drying at 100 ° under reduced pressure, the crude product melts at 253-256 °.

To a suspension of 22.8 g (0.6 moles) of lithium aluminum hydride in 3.5 liters of abs. diethyl ether and 350 ml of absolute tetrahydrofuran, a suspension of 61.4 g (0.2 mol) of 1.5-29,64582 dihydro-2H-dibenzo (2.3: 6.7) is added under stirring under a nitrogen atmosphere over a period of 30 minutes. thiepino (4,5-d) azepine-2,4 (3H) -dione in 200 ml abs. diethyl ether, keeping the temperature at 20-30 °. The reaction mixture is then refluxed for a further 24 hours and then cooled to 0-5 °. The excess lithium aluminum hydride is decomposed by careful dropwise addition of 150 ml of ethyl acetate and then 300 ml of water. The organic phase is separated, washed first with 2N hydrochloric acid and then repeatedly with water, dried over sodium sulfate and evaporated completely. The residue gives 1,3,4,5-tetrahydro-2H-dibenzo (2,3: 6,7) thiepino- (4,5-d) azepin-2-one, m.p. 195-198 °.

Example 23 · 3-Methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) dipino (4,5-d) azepine 8.38 g (0.03 mol) 2,3,4,5-Tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine is dissolved in 6 ml of 85% formic acid at 40-50 ° with stirring. . To this solution is first added 2.4 ml of a 35% formaldehyde solution and then stirred for 12 hours at an internal temperature of 95-100 °. The reaction mixture is then cooled to 20 °, diluted with 100 ml of water and basified with phenolphthalein with concentrated ammonia to give crude 3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4 .5-d) azepine is isolated as an oil. This crude base is extracted with ether, the organic phase is separated, washed twice with water and, after drying, completely evaporated over sodium sulfate. The base is converted into the methanesulphonate as follows: 8.4 g of crude base are dissolved in 40 ml of acetone and 2.6 g of methanesulphonic acid are carefully added to give 3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7 ) thiepino (4,5-d) azepine methanesulfonate crystallizes, which, after recrystallization, abs. ethanol melts at 256-258 °.

„. ... 3-ethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7)

Example 1 24: stack (4,5-d) azepine 8.38 g (0.03 mol) of 2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) ) is dissolved in 80 ml of 50% acetic acid with stirring. To this solution is added in one portion 8.16 g (0.08 moles) of acetic anhydride and allowed to stand for 12 hours at room temperature. The reaction mixture is then evaporated on a fully rotary evaporator, the residue is dissolved in ether, the ether solution is washed once with hydrochloric acid, once with 2N sodium hydroxide and twice with water. After drying over sodium sulfate, the ether solution is completely evaporated to leave 3-acetyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine as a yellow oil.

30 64582 9.4 g of crude acetyl compound are dissolved in 150 ml of absolute diethyl ether and this solution is added dropwise within one hour to a suspension of 1.6 g (0.042 mol) of lithium aluminum hydride in 50 ml of abs. diethyl ether, whereupon the reaction mixture begins to boil. It is then boiled for a further 6 hours under reflux. After cooling to 0-5 °, 40 ml of water are added to the reaction mixture and the organic phase is separated; washed with water and, after drying, evaporated completely with sodium sulphate. the oily residue is dissolved in 10 ml of acetone and cooled to -10 ° to give 3-ethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d ) azepine crystallizes, m.p. 106-107 °. The methanesulfonate is prepared according to Example 18; mp 212-214 ° (abs. From ethanol).

Example 25:

According to Example 21, the following compounds can be prepared using suitable starting materials: A) 3- (3- (dimethylamino) propyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-Diazepine from 39.3 g (0.1 mol) of 3- (3- (dimethylamino) propyl) -1,5-dihydro-2H-dibenzo (2,3: 6,7) thiepino ( 4,5-d) azepine-2,4 (3H) -dione and 14.6 g (0.38 moles) of lithium aluminum hydride in absolute diethyl ether 3- (3- (dimethylamino) propyl) -2.3 , 4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine as a crude product, dihydrochloride melting point 285-289 ° (dec.).

The starting material can be prepared as follows:

To a suspension of 30.7 g (0.1 mol) of 1,5-dihydro-2H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine-2,4 (3H) dione in 14.6 g (0.12 moles) of freshly distilled 3- (dimethylamino) propyl chloride and 31,64582 600 ml of abs. toluene, is added dropwise with stirring and refluxing under nitrogen for 2 hours a suspension of 2.3 g (0.1 mol) of lithium aluminum hydride in 6.9 ml of abs. toluene. The reaction mixture is then refluxed for 20 hours and cooled to room temperature. Add 100 ml of water, separate the organic phase and extract this three times with 50 ml of 10% methanesulphonic acid each time. The acidic extracts are made alkali with phenolphthalein with concentrated ammonia to give 3- (3- (dimethylamino) propyl) -1,5-dihydro-2H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine-2, 4 (3H) -Dione separates as crystals which, after recrystallization from ether / pentane, melts at 102-103 °.

The methanesulfonate is prepared as follows: 30 g of base (0.076 mol) are dissolved in 75 ml of acetone and 7.3 g of methanesulfonic acid (0.076 mol) are carefully added to give 3- (3- (dimethylamino) propyl) -1,5-dihydro -2H-Dibenzo- (2,3: 6,7) thiepino (4,5-d) azepine-2,4 (3H) -dione methanesulfonate crystallizes, which, after recrystallization from methanol, melts at 270-275 ° with decomposition.

B) 3- (3- (Dimethylamino) propyl) -1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine 37.4 g (0.1 mol) of 3- (3- (dimethylamino) propyl) -5,10-32 6 4 5 8 2 dihydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d ) azepine-2,4 (3H) -dione and 14.6 g (0.38 moles) of lithium aluminum hydride abs. in diethyl ether 3- (3- (dimethylamino) propyl) -1,2,3,4,5,10-hexahydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine, m.p. .p. 80-82 ° (from pentane); dihydrochloride m.p. about 315 ° (decomp.).

The starting material can be prepared as follows: from 28.9 g (0.1 mol) of 5,1O-dihydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine-2,4 (1H, 3H) -dione, 14.6 g (0.12 moles) of 3- (dimethylamino) propyl chloride and 2.3 g (0.1 moles) of lithium amide 3- (3- (dimethylamino) propyl ) -5,10-dihydro-dibenzo- (3,4: 6,7) cyclohepta (1,2-d) azepine-2,4 (1H, 3H) -dione, m.p. 113-115 ° (from hexane); hydrochloride m.p. 265-168 ° (from ethanol).

5,1O-Dihydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine-2,4- (1H, 3H) -dione is prepared by the following steps: From 189 g (0.5 moles) 10,11-bis- (bromomethyl) -5H-dibenzo- (a, d) cycloheptane (DOS 2 125 654) in 2.5 liters of acetonitrile and 59 g (1.2 moles) of sodium cyanide 5H-dibenzo (a , d) cyclohepten-10,11-diacetonitrile, m.p. 217-220 ° (from acetonitrile); 135 g (0.5 mol) of 5H-dibenzo (a, d) cyclohepten-10,11-diacetonitrile in 2.75 liters of methylene chloride with dry hydrogen bromide 2-amino-4-bromo-1,1O-dihydro-dibenzo ( 3,4: 6,7) cyclohepta (1,2-d) -azepine hydrobromide, crude; 86.5 g (0.2 mol) of 2-amino-4-bromo-1,1O-dihydro-dibenzo (3,4: 6,7) cyclohepta (1,2-d) azepine hydrobromide, 1, 5 liters of dimethylformamide and 1.3 liters of water 5,10-dihydro-dibenzo- (3,4: 6,7) cyclohepta (1,2-d) azepine-2,4 (1H, 3H) -dione, m.p. . 265-268 ° (from acetone).

Example 26: 3-Butyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine

According to Example 5, using the corresponding starting materials, the following can be prepared: from 22.7 g (0.5 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) thiepine, 4.4 g: (0.06 moles) of n-butylamine and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 3-butyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine, m.p. 107-108 ° (from acetone); methanesulfonate m.p. 218-220 ° (abs. From ethanol).

33 6 4 5 8 2

Example 27; 3-allyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -tiepino (4,5-d) azepine

According to Example 5, using the corresponding starting materials, the following can be prepared: from 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) thiepine, 3.4 g: (0.06 moles) of allylamine and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 3-allyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine as a crude product; methanesulfonate m.p. 225-227 ° (abs. Ethanol).

Example 28; 3-Propynyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine

According to Example 5, using the corresponding starting materials, the following can be prepared: from 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) thiepine, 3.3 g: (0.06 moles) of propargylamine and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 3-propynyl-2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7) thiepino (4,5-d) azepine as a crude product; methanesulfonate m.p. 218-221 ° (abs. From ethanol).

Example 29; 3- (sykJopentyylimetyyli) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) road surfaces (4,5-d) azepine

According to Example 5, using the corresponding starting materials, 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) thiepine, 6.0 g ( 0.06 moles) of (aminomethyl) cyclopentane and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine m.p. 113-115 ° (abs. From ethanol); methanesulfonate m.p. 248-252 ° (abs. From ethanol).

Example 30: 3- (Cyclohexylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine

According to Example 5, using the corresponding starting materials, the following can be prepared: 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo b, f-thiepine, 6.7 g (0, 06 moles) of (aroinomethyl) cyclohexane and 16.5 g (0.125 moles) of diisopropylethylamine abs. in ethanol 3- (cyclohexylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine, m.p. 113-115 ° (from acetone); methanesulfonate m.p. 256-258 ° (abs. Ethanol-34 64582 list).

Example 31: 1,2,4,5-Tetrahydro-3H-dibenzo (2,3: 6,7) thiepino (4,5-d) -azepine-3-ethanol

According to Example 5, using the corresponding starting materials, the following can be prepared: from 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) -ethyl) -dibenzo b, f-thiepine, from 3.7 g (0, 06 moles) of ethanolamine and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 1,2,4,5-tetrahydro-3H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine-3-ethanol, m.p. 157-159 ° (from acetone); methanesulfonate m.p. 194-198 ° (abs. From ethanol).

Example 32; 1,2,4,5-tetrahydro-3H-dibenzo (2,3: 6,7) road surfaces (4,5-d) azepine-3-propanol

According to Example 5, using the corresponding starting materials, the following can be prepared: 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo b, f-thiepine, 4.5 g (0, 06 moles) of 3-aminopropanol and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 1,2,4,5-tetrahydro-3H-dibenzo (2,3: 6,7) thiepino- (4,5-d) azepine-3-propanol, m.p. 120-132 ° (from acetone); methanesulfonate m.p. 181-183 ° (abs. From ethanol).

Example 33; 3- (3-methoxypropyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) road surfaces (4,5-d) azepine

According to Example 5, using the corresponding starting materials, the following can be prepared: 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo b, f-thiepine, 5.4 g (0, 06 moles) of 3-methoxypropylamine and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 3- (3-methoxypropyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine as a crude product, methanesulfonate m.p. 213-216 ° (abs. From ethanol).

Example 34; 3- (3- (methylthio) propyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine

According to Example 5, using the corresponding starting materials, the following can be prepared: 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) thiepine, 6.3 g ( 0.06 moles) of 3- (methylthio) propylamine and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 3- (3- (methylthio) propyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine as crude 64582; methanesulfonate m.p. 212-214 ° (abs. From ethanol).

Example 35: 3- (2- (Methylthio) ethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine

According to Example 5, using the corresponding starting materials, the following can be prepared: from 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) thiepine, 5.5 g: (0.06 moles) of 2- (methylthio) ethylamine and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 3- (2- (methylthio) ethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine, m.p. . 91-92 ° (from pentane); methanesulfonate m.p. 218-220 ° (abs. From ethanol).

Example 36: 7-Chloro-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine

According to Example 5, using the corresponding starting materials, the following can be prepared: from 24.5 g (0.05 mol) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-chloro-dibenzo (b, f) thiepine, 1 .85 g (0.06 mol) of methylamine and 16.25 g (0.125 mol) of diisopropylethylamine in methanol 7-chloro-3-methyl-2,3,4,5-tetrahydro-1H -dibenzo (2,3: 6,7) thiepino (4,5-d) azepine as a crude product; hydrochloride m.p. 266-268 ° (abs. From ethanol).

According to Example 5, the starting material can be prepared as follows: from 43.1 g (0.1 mol) of 2-chloro-10,11-bis- (bromomethyl) -dibenzo (b, f) thiepine and 11.8 g g of sodium cyanide in 500 ml of acetonitrile 2-chloro-dibenzo (b, f) thiepine-10,11-diacetonitrile, m.p. 207-210 ° (from chloroform); 32.3 g (0.1 mol) of 2-chloro-dibenzo (b, f) thiepine-10,11-diacetonitrile, 400 ml of methanol, 3.8 ml of water and dry hydrogen chloride 2-chloro-dibenzo (b, f) thiepine-10,11-diethylacetic acid dimethyl ester, m.p. 111-113 ° (methanol); 38.9 g (0.1 mol) of 2-chloro-dibenzo (b, f) thiepine-10,11-diacetic acid dimethyl ester and 7.6 g (0.2 mol) of lithium aluminum hydride per liter of abs . diethyl ether 2-chloro-dibenzo- (b, f) thiepine-10,11-diethanol, m.p. 152-154 ° (from ethyl acetate); and 33.3 g (0.1 mol) of 2-chloro-dibenzo (b, f) thiepine-10,11-diethanol, 25.2 g (0.22 mol) of methanesulphonic acid chloride 36 64582 in 120 ml of pyridine, 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-chloro-dibenzo (b, f) thiepine, m.p. 118-120 ° (from diethyl ether).

Example 37; 7-chloro-3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) road surfaces (4,5-d) azepine

According to Example 5, using the corresponding starting materials, the following can be prepared: from 24.5 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-chloro-dibenzo (b, f) thiepine, 6.7 g (0.06 moles) of (aminomethyl) cyclopentane and 16.25 g (0.125 moles) of diisopropylethylamine abs. in ethanol 7-chloro-3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine, m.p. . 123-126 ° (from acetone); methanesulfonate m.p. 195-198 ° (abs. Ethanol).

Example 38: a) 3- (Cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -oxepino (4,5-d) azepine

To a solution of 21.9 g (0.05 mol) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenzo (b, f) oxepine in 250 ml of abs. ethanol, 6 g (0.06 mol) of aminomethylcyclopentane and 16.25 g (0.125 mol) of diisopropylethylamine are added and the reaction mixture is refluxed for 18 hours. After cooling, the ice bath separates crystals which are filtered off with suction and washed with a small amount of isopropanol and pentane. The filtration residue is 3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -oxepino (4,5-d) azepine, m.p. 99-101 °. Methanesulfonate m.p. 280 °, decomp.

In a similar manner, the following can be prepared: b) 1,2,4,5-Tetrahydro-3H-dibenz (2,3: 6,7) oxepino (4,5-d) azepine-3-propanol from 21.9 g (0 .05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) dibenz (b, f) oxepine, 4.5 g (0.06 moles) of 3-aminopropanol and 16.25 g of (0.125 moles) diisopropylethylamine abs. in ethanol 1,2,4,5-tetrahydro-3H-dibenz (2,3: 6,7) oxepino- (4,5-d) azepine-3-propanol, m.p. 59-61 ° (from pentane); methanesulfonate m.p. 188-192 ° (abs. From ethanol).

Example 39: 3,10-Dimethyl-1,2,3,4,5,10-hexahydro-dibenz (b, f) -azepino (4,5-d) azepine 27.6 g (0.1 mol) of 3-methyl -1,2,3,4,5,10-hexahydro-dibenz-64582 37 (b, f) Azepino (4,5-d) azepine is dissolved in a mixture of 130 ml of hexametapol and 130 ml of abs. toluene, while stirring. To this solution is added dropwise over 15 minutes a suspension of 7.8 g (0.2 moles) of sodium amide in 24 ml of abs. toluene, and the temperature is maintained at 18-20 ° with slight cooling; at the same time, a stream of dry nitrogen gas is passed through the reaction solution to remove the ammonia formed. At the end of the dropwise addition, stir for a further 30 minutes and then add dropwise a solution of 14.2 g (0.1 mol) of methyl iodide in 100 ml of abs. toluene for 15 minutes, maintaining the temperature at 18-20 ° with ice cooling. The reaction mixture is then stirred for a further 1 to 5 minutes and then slowly poured into a mixture of 2 liters of water and 400 ml of toluene. The organic phase is separated and the aqueous phase is extracted with toluene. The combined organic solutions are washed with water and, after drying over potassium carbonate, completely evaporated in vacuo. The crystalline residue, 3,10-dimethyl-1,2,3,4,5,10-hexahydro-dibenz (b, f) azepino (4,5-d) -azepine, is recrystallized from ethanol and melts at 197-199 °. in; methanesulfonate m.p. 231-133 ° (abs. From ethanol).

The starting material can be prepared according to Example 13 as follows: from 42.1 g (0.1 mol) of 5-acetyl-10,11-bis- (bromomethyl) -5H-dibenz (b, f) azepine and 11.8 g (0.24 mol) of sodium cyanide in 500 ml of acetonitrile 5-acetyl-5H-dibenz (b, f) azepine-10,11-diacetonitrile, m.p. 183-185 ° (from benzene); 31.3 g (0.1 mol) of 5-acetyl-5H-dibenz (b, f) azepine-10.11-diacetonitrile, 400 ml of methanol, 3.8 ml of water and dry hydrogen chloride in 5-acetyl- 5H-Dibenz (b, f) azepine-10,11-diacetic acid dimethyl ester, m.p. 123-124 ° (from toluene); 37.9 g (0.1 mol) of 5-acetyl-5H-dibenz (b, f) azepine-10.11-diacetic acid dimethyl ester and 7.6 g of lithium aluminum hydride in 150 ml of abs. tetrahydrofuran 5-ethyl-5H-dibenz- (b, f) azepine-10,11-diethanol, m.p. 102-105 ° (from ether); 30.9 g (0.1 mol) of 5-ethyl-5H-dibenz (b, f) azepine-10.11-diethanol and 25.2 g (0.22 mol) of methanesulphonic acid chloride in 120 ml of pyridine 10, 11-bis- (2- (methylsulfonyloxy) ethyl) -5-ethyl-5H-dibenz (b, f) azepine, m.p. 140-143 ° (from toluene); 38 64582 37.9 g (0.1 mol) of 5-acetyl-5H-dibenz (b, f) azepine-10.11-diacetic acid dimethyl ester and 7.6 g of lithium aluminum hydride per liter of abs. diethyl ether 5H-dibenz (b, f) azepine-10.11-diethanol, m.p. 180-182 ° (from acetone); 28.1 g (0.1 mol) of 5H-dibenz (b, f) azepine-10,11-diethanol and 25.3 g (0.22 mol) of methanesulphonic acid chloride in 120 ml of pyridine 10, 11-bis- (2- (methylsulfonyloxy) -ethyl) -5H-dibenz (b, f) azepine, m.p. 140-142 ° (from toluene); 21.9 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -5H-dibenz (b, f) azepine, 1.85 g (0.06 moles) of methyl amine and 16.25 g (0.125 mol) of diisopropylethylamine 3-methyl-1,2,3,4,5,10-hexahydro-dibenz (b, f) azepino (4,5-d) ) -azepine, m.p. 121-124 ° (from methane); methanesulfonate m.p. 263-266 ° (abs. From ethanol / acetone).

Example 40; 7-chloro-3-methyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) oxepino (4,5-d) azepine

According to Example 11, the following compounds can be prepared using the corresponding starting materials: from 23.6 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-chloro-dibenz (b, f) oxepine , 1.85 g (0.06 mol) of methylamine and 16.25 g of diisopropylethylamine abs. in ethanol 7-chloro-3-methyl-2,3,4,5-tetrahydro-1H-dibenz (2,3: 6,7) -oxepino (4,5-d) azepine, m.p. 174-176 ° (from toluene); hydrochloride sul.p. 279-281 ° (abs. From ethanol).

The starting material, 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-chloro-dibenz (b, f) oxepine can be prepared according to Example 11 as follows.

a) 20.7 g (0.05 mol) of 10,11-bis- (bromomethyl) -2-chloro-dibenz (b, f) oxepine and 5.9 g (0.12 mol) sodium cyanide in 250 ml of acetonitrile 2-chloro-dibenz (b, f) oxepine-10,11-diacetonitrile, m.p. 227-230 ° (from methanol); b) 15.3 g (0.05 mol) of 2-chloro-dibenz (b, f) oxepine-10.11-diacetonitrile, 200 ml of methanol, 1.9 ml of water and dry hydrogen chloride in 2-chloro- dibenz (b, f) oxepine-10,11-diethylacetic acid dimethyl ester, crude product (oil); c) 18.7 g (0.05 mol) of 2-chloro-dibenz (b, f) oxepine-10.11-diacetic acid dimethyl ester and 3.8 g (0.1 mol) of lithium aluminum hydride in 500 ml: in diethyl ether 2-chloro-dibenz- (b, f) oxepine-10,11-ethanol, crude product (oil); and 64582 39 d) 15.8 g (0.05 moles) of 2-chloro-dibenz (b, f) oxepine-10,11-diethanol, 12.6 g (0.11 moles) of methanesulfonic acid chloride In 60 ml of pyridine, 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-chloro-dibenz (b, f) oxepine, crude product (oil).

Example 41;

Examples 5 and 10, respectively, using the corresponding starting materials, the following compounds can be prepared: A) 3-Propyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) -azepine from 22.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) -ethyl) -dibenzo (b, f) thiepine, from 3.3 g (0.06 moles) of propyl amine and 16.25 g of diisopropylethylamine abs. in ethanol 3-propyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) -azepine, m.p. 128-130 ° (from acetone); methanesulfonate m.p. 181-183 ° (abs. From ethanol).

B) 7-Bromo-3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7) thiepino (4,5-d) azepine from 26.7 g (0 .05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-bromo-dibenzo (b, f) thiepine, 6.0 g (0.06 moles) of (aminomethyl) -cyclopentane and 16.25 g (0.125 mol) of diisopropylethylamine 7-bromo-3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4 , 5-d) azepine, m.p. 12ΟΙ 23 ° (from ethanol); C) 7-Bromo-3-ethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino- (4,5-d) azepine from 26.7 g (0.05 moles) of 10,11-bis- (2- (methylsulfonyloxy) ethyl) -2-bromo-dibenzo (b, f) thiepine, 2.7 g (0.06 moles) of ethylamine and 16.25 g of (0.125 mol) diisopropylethylamine 7-bromo-3-ethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine, the crude product.

Example 42: 7-Cyano-3-ethyl-2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7) thiepino (4,5-d) azepine

A mixture of 19.3 g (0.05 mol) of 7-bromo-3-ethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5- d) azepine (prepared according to Example 4), 10.7 g (0.12 moles) of copper I-cyanide in 20 ml of dimethylformamide are heated under a nitrogen atmosphere for 22 hours with stirring at 180 °. It is then cooled to 30 °, diluted with 100 ml of methylene chloride and 50 ml of a 50% aqueous solution of ethylenediamine are added. The organic phase of the residue is separated off, washed with water and, after drying over sodium sulphate, evaporated to dryness. The crystalline residue, 7-cyano-3-ethyl-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino- (4,5-d) azepine, melts after recrystallization from hexane / acetic acid. from ethyl acid at 154-156 °.

To convert the base to the methanesulfonate, 10 g (0.03 moles) of the base are dissolved in 50 ml of acetone, and 2.88 g (0.03 moles) of methanesulfonic acid are added to this solution with stirring, whereby 7-cyano-3-ethyl-2,3,4 , 5-Tetrahydro-1H-dibenzo (2,3: 6,7) thiepino- (4,5-d) azepine methanesulfonate crystallizes, m.p. 220-223 °. In a similar manner can be prepared: B) 7-Cyano-3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7) thiepino (4,5-d) azepine 22 g (0.05 mol) of 7-bromo-3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) thiepino (4,5-d) azepine , 10.7 g (0.12 mol) of copper 1-cyanide in 20 ml of dimethylformamide 7-cyano-3- (cyclopentylmethyl) -2,3,4,5-tetrahydro-1H-dibenzo (2 , 3: 6,7) thiepino (4,5-d) azepine, m.p. 170-172 ° (methanol); methanesulfonate m.p. 203-206 ° (abs. From ethanol).

Claims (6)

A process for the preparation of 1,2,3,4,5,1 O-hexahydro-dibenzo (3,4: 6,7) cyclohepta- (1,2-d) azepines suitable for the treatment of agitation state and analogues of -O-, -S- or -NR3 ~ in the 10-position of formula I1 ((I), __ Λ __ in which denotes hydrogen, lower alkyl of 6 carbon atoms, cycloalkyl lower alkyl of 10 carbon atoms, lower alkenyl with not more than 8 carbon atoms, lower alkoxyl lower alkyl with not more than 4 carbon atoms, di-alkoxy lower alkoxy with no more than 10 carbon atoms methyl or methoxy substituted phenyl lower alkyl, and represents hydrogen, chlorine, bromine, lower alkoxy of not more than 3 carbon atoms, hydroxy, lower alkoxy of not more than 3 carbon atoms, lower alkoxy of not more than 3 carbon atoms, or cyan, X represents epoxy, epithelial or methyl \ /? da) R 3 which represents hydrogen or lower alkyl having not more than 4 carbon atoms, and acid addition salts thereof, characterized in that a) a reactive diester of a diethanol of formula E-CH_ CH-EI 2 I 2 in which E represents acid residue of a strong inorganic or organic acid, is reacted with an amine of formula R 1 N 1 to 111 H or b) to produce compounds of formula I in which R 1 represents the group R 1, which means the same as R 2, with the exception of alkanoyloxy lower alkyl, a compound of the formula Qw (iv) reducing at least one of the symbols Q1 and denoting an oxygen atom and the other optionally two hydrogen atoms, and, if desired, - a obtained compound of formula I, wherein R1 represents vcite, being converted into a compound of formula I , in which R 1 has any other meanings as defined above, - a obtained compound of formula I / in which represents a hydroxyl lower alkyl group, by acylation is converted into a compound of formula I in which represents an alkanoyloxy lower alkyl group, - represents a phenyl-lower alkyl group by hydrogenolysis is converted into a compound of formula I in which R 2 represents hydrogen, - a obtained compound of formula I in which X represents a divalent residue having is hydrogen, is converted into a compound of formula I in which R3 is lower alkyl, - a obtained compound in which substituent R2 represents lower alkoxy is boiled with hydrochloric acid for formation of compounds in which the ring substituent is hydroxy, - in a recovered compound, cyan is introduced as substituent R2, and / or, if desired, a recovered free compound is transferred into a site, and / or, if desired, a received site is transferred into the free compound or in another site, and / or, if desired, a obtained isomer mixture is divided into the individual isomers. Process according to Claim 1, characterized in that 3-methyl-2,3,4,5-tetrahydro-1H-dibenzo [(2,3: 6,7) tiepino (4,5-dj azepine) is prepared. Process according to claim 1, characterized in that 3-methyl-2,3,4,5-tetrahydro-1H-dibenzo- (2,3: 6,7) oxepino (4,5-d) azepine is prepared. Process according to claim 1, characterized in that 3-methyl-7-cyano-2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) tiepino (4,5-d) is prepared. ) azepine. 5. A process according to claim 1, characterized in that 3-methyl-1,2,3,4,5,10-hexahydro-dibenzo [3,4: 6,7] cyclohepta (1,2-d) is prepared. azepine. Process according to Claim 1, characterized in that 3- (2,3,4,5-tetrahydro-1H-dibenzo (2,3: 6,7) -thiepino (4,5-d) azepine-3 is prepared) -Y 1) propanol.