DD212511A5 - METHOD FOR THE PRODUCTION OF DIBENZAZEPINE CARBOXAMIDES - Google Patents

Abstract

5H-dibenzo (b, f) azepine-5-carboxamides of general formula I, wherein R is low and R independently of one another are hydrogen or lower alkyl, or lower alkylene or ethyleneoxyethylene joined together, one of the symbols X deep 1 and X. deep 2 and / or the symbol X deep 3 lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl and X deep 3 also halogen to atomic number 35, cyano or di-lower alkylsulfamoyl and the two remaining symbols X deep 1, X deep 2 and X are deep 3 hydrogen, but at the same time with lower alkyl as X deep 1 also X deep 2 lower alkyl, or, if at least one of the radicals R is deep 1 and R 2 deep different from hydrogen or Y deep 1 and Y deep 2 Represent hydrogen, X deep 1, X deep 2 and X deep 3 each hydrogen, X deep 4 hydrogen means or together with halogen or lower alkyl as X deep 3 also one of these Radicals and Y deep 1 and Y deep 2 together an additional bond or, if X is deep 1 and / or X 2 deep lower alkyl or hydrogen, both hydrogen, or, if at least one of the radicals R deep 1, R deep 2, X deep 3 and X deep 4 is different from hydrogen, X deep 1 also halogen up to atomic number 35 or cyano, X deep 2 hydrogen and Y deep 1 and Y deep 2 together an additional bond, or X deep 1 and Y deep 1 together the oxo radical and X is deeply 2 and Y is deeply 2 each hydrogen or X deep 1 hydroxy and X deep 2, Y deep 1 and Y deep 2 each hydrogen, or where R deep 1 is lower alkyl, R deep 2, X deep 3 , X deep 4, Y deep 1 and Ytief 2 represent hydrogen and X deep 1 and X deep 2 together represent epoxy or epimethylene, exhibit nootropic effects and are suitable for the treatment of cerebral insufficiency. The invention relates to a treatment method characterized by the administration of such a compound, pharmaceutical preparations suitable for this purpose as well as novel compounds of the formula I and analogy processes for their preparation.

Description

-γ-

Berlin, 22.3.1984 AP O 07 D / 255 o47 / 8 63 046/11

Process for the preparation of dibenzazepine carboxoxides Field of application of the invention

The present invention relates to a process for preparing 5H-dibenz / fb, f_7a2epin-5 ~ carboxamides of the general formula I

^: i ^ i ^

"- ti ι

^x 4-k ¹ I Λ- h

The compounds prepared according to the invention are used as medicaments for the prophylaxis or therapy of cerebral insufficiency, in particular of memory disorders.

Characteristic of the known technical solutions

Compounds of the general formula I in which X _{1 is} lower alkyl, R ₂ and R p are hydrogen or lower alkyl, X ₂ , X 1 and X, each is hydrogen and Y is ^. and I ₂ together represent an additional bond are described in the GH-PS Hr. 500 as intermediates, namely 10-methoxy-

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in-5 "boramide, N-methyl-, H, I-dimethyl- _,? -butyl-, L, N,? -dibutyl-10? -nit? iox3 ^r -5H-dibenz / _i ? b, f7-azepine-5 -carboxamide.

Further, in the GH-PS Hr. 325 662, 403 767, 500 TOI and 501 196, GB-PS No. 906 452, BP-OS No. 50 589 and in BE-PS No., 892 882 compounds of the formula I, wherein ' j R., and Rp are as defined, X and X ₂ is hydrogen or lower alkyl or * 3ofern R. and R ₂ are hydrogen or lower alkyl, X is hydroxy and X ₂ is hydrogen, X_ and X is hydrogen or, provided that X, and X _{2 is} halogen or lower alkoxy and X, halogen or lower alkyl, where Y and Yp are each hydrogen or together represent an additional bond, are described as anticonvulsants. Further, in US Pat. 3,842,091 and in JP patent application Hr. 7308631 compounds of formula I wherein R. is lower alkyl X ₁ together with X ₂ or Spoxy Spimethylen and R ₂ JX, X, Y and Y ₂ is hydrogen, described as anticonvulsants. Further, in US Patent No. 4,235,895, BE Patent No. 833,852 and ISP Patent Application No. 50 compounds of formula I wherein R ₁ , R ₂ , X and X are hydrogen, X "is cyano or hydroxy and X _{2 is} hydrogen or ··· X ₁ halogen and X _{2 is} hydrogen or halogen or X ₁ and X _{9 are} hydrogen and X 1 is cyano and Y ₁ and Y ₂ together are an additional bond or, if X _{1 is} hydroxy, hydrogen have been described as anticonvulsants and some of them have been proposed in the unpublished BE-PS Nr, 892 882 as nootropics. ,

Aim of the invention; '

The aim of the invention is to provide "nootropic" active drug substances,

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Explanation of the essence of the invention

The invention has for its object to find new compounds with the desired properties and processes for their preparation.

According to the invention, novel 5H-dibenz / b, f / azepine-5-carbo; xamides of the general formula I are prepared in which R.sup.a and R.sup.p independently of one another represent hydrogen or lower alkyl.l, or together with alkylene or ethyleneoxyethylene, one of the symbols Z _{1 and} X are lower alkylthio, lower alkylsulphinyl, - lower alkylsulphonyl, trifluoromethyl, I-lower alkoxy, halogen of the azo number bis and with 35 or cyano and the other hydrogen, medaralkyl, lower alkoxy, lower alkylthio, lower alkylsuifinyl, lower alkylsulfonyl or trifluoromethyl or both symbols Z and Xp X represents hydrogen, X, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, l'rifluoromethyl, halogen of the atomic limes to and with 35, cyano or di-lower alkylsulfainoyl or, if appropriate

at least one of the radicals Σ. and

different from hydrogen

is and at the same time with halogen or cyano as X. or

and

Hydrogen as

or,

alkyl and

R. hydrogen or song

Uiederalkyl or R. together with R "Nieder-

, together with R "alkylene or Aethylenoxyäthylen and at the same time with Hiederalkoxy as X ₁

or X and hydrogen as X ₇ or XR together with R _? X may also be hydrogen, X is hydrogen or .Can also be one of these radicals with lower alkyl or halogen as X, and the symbols Y and Y ₇ , if one of the symbols X. and X lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl and the other is hydrogen or both represent hydrogen, in each case stand for hydrogen or, if at least one of the radicals R, R, X and X of hydrogen or X of cyano or at least one of the radicals X_ and X, is different from halogen , together represent an additional bond, or in which R and R together represent lower alkylene or Aethylenoxyäthylen and X together with Y is oxo and X and Y _{7 is} hydrogen or X hydroxy and X, Y and Y is hydrogen or R and R ₇ independently Lower alkyl or together are lower alkylene or Aethylenoxyäthylen, X together with X ₇ epoxy or epimethylene u and each of Y ₇ and Y ₇ is hydrogen, X is hydrogen, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, halogen of atomic number to and including 35, cyano or di-lower alkylsulfamoyl, and X is hydrogen or simultaneously lower alkyl or halogen as X ₃ also represents one of these radicals. These are able to reduce the amnesiogenic effect of the electric shock both in a dosage which completely or considerably reduces the convulsions induced by the electric shock, eg to 50% according to the anticonvulsant ED and partly still in lower dosages, to at least a similar or even greater extent as piracetam.

The findings summarized above can be determined in the following one-step learning test on mice:

The test device consists of a large box (35 χ 20 χ 10 cm), which is connected by a sliding door with a small box (10 χ 10 χ 18 cm) · While the small box is brightly lit by a 100 watt lamp from above , the big box is dark. The floor of both compartments consists of an electrifying grate.

For training, the mice are individually placed in the brightly lit small box. Since mice have a spontaneous preference for darkness, they usually go into the dark compartment within 30 seconds. Once you have entered this completely, the sliding door is closed and a foot shock (1 mA, 5 seconds) administered. The animals are immediately removed from the device.

To test the learning effect (retest), the mice are again set individually after 24 hours in the bright compartment and the latency, until they are completely dark, measured. Usually most of the animals stay in the light compartment for the entire observation period of 150 seconds.

The learning effect is largely eliminated or the memory of the foot shock at least partially extinguished when amnesiogene treatment immediately after the foot shock of the training session, a temporal electroshock treatment is connected. Electro-shock parameters: 50 mA, 0.4 seconds, 50 Hz, 0.6 msec pulse width.

To test and compare their protective effect against the amnesiogenic effect of the electric shock, the test substances are administered intraperitoneally in each case 30 minutes before training as a suspension in Methocel and the animals are subjected to the electroshock treatment immediately after training. 24 hours later, based on the length of stay in the illuminated box, the extent of the remaining learning effect is measured and compared with that of the other test substances as well as control animals with mere Methocel administration and training without, as well as those with subsequent electroshock treatment. When according to the Mann-Whitney U-Test still significantly effective doses, i. DE. were e.g. For

mm

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10-methylthio - 5H-diberL2i / b _i f7a2; ePIN-5 - Garbozainid 0.1 mg / kg ip and · for 3-Methylaulfoxiyl - 5H '- <3ibenz / ¹ b, f7azäpin-5-CAEI ^l boxamide also 0.1 mg / kg ip, determined

As literature on similar experiments may be mentioned: 3 _a J, Sara and D, Lefevre, Psychopharmacölogia _25, 32-40 (1972), hypoxia-induced amnesia in one-trial learning and pharmacological protection by piracetain; and Boggan, WO, and Schlesinger, K. _r in Behavioral Biology.J2, 127-134 (1974).

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The compounds of formula I can be used for the prophylaxis or therapy of cerebral insufficiency, in particular of memory disorders of various origins, such as senile dementia, multi-infarct dementia or Alzheimer-type dementia, and also subsequent brain traumas or apoplexy.

The dosage depends on the type of disorder, the individual condition, age and weight of the patient and the duration of treatment and is in particular between about 0.2 and about 17 mg / kg per day or, about 15 to 1200 mg per day for adults of normal weight of about 70 kg.

The invention relates, for example, to a process for the preparation of compounds of the formula I in which R and E independently of one another are hydrogen or lower alkyl or lower alkylene or ethyleneoxyethylene, one of the two symbols X.sup.1 and X.sup.p and / or the symbol X.sup.-, liederalkylthio, Miederalkylsulfinyl, Hiederalkylsulfonyl or trifluoromethyl and X- also halogen to atom number 35? Diniederalkylsulfamoyl, Efiederalkyl, cyano or Hiederalkoxy means and the or the remaining two of the symbols X., Xo ^and 3 2_ hydrogen, but X. or Σ, -, if at least one of the radicals R. and R _? of hydrogen and itfiederalkyl or one of the radicals X., and X. is different from hydrogen and Y ^ and Y _{2 represent} ^an additional bond.

len, also lower alkoxy and X or X can denote hydrogen, X.

2 1 *

Is hydrogen or at the same time as X may also be one of these radicals together with halogen or lower alkyl, Y] _ and Y together represent an additional bond or at the same time may denote hydrogen with hydrogen as X and X ", or if at least one of the radicals R and R is different from hydrogen and X and X are hydrogen, X _{1 can} also be halogen to atom number 35 or cyano, X "hydrogen and Y and Y together may represent an additional bond.

The invention relates in the first place to a process for the preparation of compounds of the formula I in which R and R independently of one another are hydrogen or lower alkyl or lower alkylene or ethyleneoxyethylene, one of the two symbols X and X "lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or tr X is hydrogen, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano, halogen to atomic number 35, di-lower alkylsulfamoyl, lower alkyl or lower alkoxy, X, hydrogen or at the same time also signify one of these radicals with halogen or lower alkyl as X. can and Y and Y together represent an additional bond or each hydrogen.

The invention also relates in the first place to the preparation of compounds of the formula I in which R ₁ and R "are independently hydrogen or lower alkyl or lower alkylene or ethyleneoxyethylene, X and X are hydrogen, X _ is halogen of the atomic number up to and including 35, lower alkyl , Lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano or di-lower alkylsulfamoyl, X means hydrogen or at the same time. Halogen or lower alkyl as X may also represent one of these radicals and Y and Y "respectively

Hydrogen or, if at least one of the radicals R and R is hydrogen or X- of cyano or X. Other than halogen, together constitute an additional bond.

The invention further relates in the first place to the preparation of compounds of the formula I in which one of the symbols R and R _{2 is} lower alkyl and the other hydrogen or both are lower alkyl or together are lower alkylene or Aethylenoxyäthylen, one of the symbols X and X is halogen of the atomic number to and with 35 or cyano and the other as well as X "and X, are hydrogen, wherein Y and Y together represent an additional bond.

The invention also relates primarily to the preparation of compounds of

Formula I wherein R and R are independently hydrogen or lower alkyl or lower alkylene or ethyleneoxyethylene joined together, X and Y together are oxo and X and Y are each hydrogen or X ₁ lower alkoxy or hydroxy and X ₁ , Y and Y are each hydrogen, X for halogen of the atomic number up to and including 35, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano or di-lower alkylsulfamoyl or, if R and R together are lower alkylene or Äthethylenoxyäthylen, is hydrogen and X is hydrogen or at the same time with halogen or lower alkyl as X can also mean one of these radicals.

The invention relates above all

the preparation of compounds of the formula I in which on the one hand R, R, X and X are hydrogen, X is lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl having in each case to and with C atoms, such as methylthio or methylsulfonyl, di-lower alkylsulfamoyl having up to and 4 C atoms in any alkyl moiety, such as dimethylsulfamoyl,

Lower alkyl or lower alkoxy having up to and including 4 C atoms, such as methyl or methoxy, halogen of the atomic number up to and including 35, such as chlorine, or trifluoromethyl, X. is hydrogen or at the same time as lower alkyl or halogen may be lower alkyl and Y and Y "each represent hydrogen or together represent an additional bond, or wherein on the other hand R and R independently of one another represent hydrogen or lower alkyl, each having and having 4 carbon atoms and, for example, methyl, one of the radicals X and X "lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl having in each case up to and with 4 C atoms, such as methylthio or methylsulfonyl, trifluoromethyl or, if at least ¹ of the radicals R ₁ and R is lower alkyl, halogen of the atomic number to and with 35, such as chlorine or bromine or cyano and the other and X and X, is hydrogen and Y ₁ and

3 4 .1

Y together represent an additional bond.

The invention particularly relates

the preparation of compounds of the formula I in which 5 of the symbols R ₁ , R ₃ , X ₁ , X ₃ , X ₃ and X _{4 are} hydrogen and one of them is different R and / or R is lower alkyl having up to and containing 4 C atoms such as methyl or butyl, a different radical, X or X ₂ lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl each having and to 4 C atoms, such as methylthio or methylsulfonyl, or trifluoromethyl or a different radical X "lower alkylthio, lower alkylsulfinyl or lower alkylsulfonyl with in each case up to and with 4 C atoms, such as methylthio or methylsulfonyl, di-lower alkylsulfamoyl with up to and 4 C atoms in each alkyl moiety, such as dimethylsulfamoyl, lower alkyl or lower alkoxy with up to and with 4 C atoms, such as methyl or methoxy, halogen of Atom number to and with 35, such as chlorine, or trifluoromethyl, and Y and Y together represent one, additional bond.

The invention relates in particular to the preparation of the novel compounds described in the Preparation Examples.

Above and below, "lower radicals or compounds" are preferably understood as meaning those having at most 7, in particular at most 4, carbon atoms. In the compounds of the general formula I, the general terms used may be represented, for example, by the radicals mentioned below: lower alkyl is, for example, propyl, butyl, isobutyl, pentyl, isopentyl, neopentyl, hexyl, heptyl and especially methyl or, in particular, X.sup.1 in addition to hydrogen as X. , Aethyl, lower alkylene is, for example, 4- to 6-membered and accordingly forms together with the adjacent nitrogen atom, for example 1-pyrrolidinyl, 2,5- and 3,4-dimethyl-1-pyrrolidinyl, 1-piperidinyl, 4-methyl, 2,6-dimethyl- or 4,4-dimethyl-1-piperidinyl or hexahydro-1H-azepin-1-yl. Lower alkoxy is, for example, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, pentyloxy, isopentyloxy, neopentyloxy, hexyloxy, heptyloxy and especially methoxy. Lower alkylthio is, for example, ethylthio, propylthio, isopropylthio, butylthio or isobutylthio and above all methylthio, lower alkylsulfinyl, for example methylsulfinyl or ethylsulfinyl and lower alkylsulfonyl, for example ethylsulfonyl, propylsulfonyi, isopropylsulfonyl, butylsulfonyl or isobutylsulfonyl and, above all, methylsulfonyl. Halogen up to atomic number 35 is fluorine, bromine and, above all Chlorine, and Dxniederalkylsulfamoyl eg dimethylsulfamoyl or diethylsulfamoyl. A substituent X-, for example, is in the 2-position or especially in the 3-position. If such X. X is equal to ₃ lower alkyl or halogen, preferably X is provided at the same distance from the nitrogen atom of the middle ring, ie for example are methyl groups or chlorine atoms, and X in X_

3 4

2,8- or preferably in the 3,7-position of the tricycle.

The pharmaceutical preparations can be single dose dosage forms, i. Can unit forms for oral administration,

- 10 -

such as tablets, dragées or capsules, or for rectal administration such as suppositories, or non-unit dosage forms for oral administration such as syrups. Dosage unit forms contain a compound of the general formula I in an amount which is suitable for taking the abovementioned daily dose in a single or multiple, preferably at most three, in particular twice administration of in each case preferably one or two dose units, i. the total or one-third, or more particularly half, of a daily dose, or one-half, one-sixth or one-fourth, corresponding to about 2.5 to about 600 mg, preferably about 5 to about 300 mg. Instead of a single compound of general formula I, several can be administered together, with the total doses and amounts also remain in the range given above for Einzelverb indungen.

Divisible unit dosage forms such as breakable tablets and sustained release tablets may also contain higher levels of drug and, on the other hand, dosage unit forms for administration to children may also contain correspondingly lower levels of drug.

Non-dosage formulated oral dosage forms, such as syrups, contain those amounts of the active ingredients in appropriate amounts or volume units of e.g. 2.5, 5 or 10 ml.

The pharmaceutical preparations preferably contain one or more compounds of general formula I, together with inorganic or organic, solid or liquid, pharmaceutically acceptable excipients which are suitable for enteral, e.g. suitable for oral administration. For the production of tablets or dragee cores, the active ingredients are combined, e.g. with solid powdery carriers, such as lactose, dextrose, saccharose

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rose, mannitol, sorbitol, cellulose and / or glycine, optionally with the addition of lubricants, e.g. Silica, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and / or polyethylene glycol, optionally with the addition of 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, disintegrants, e.g. starches, agar, alginic acid or salts thereof, such as sodium alginate, and / or effervescent mixtures, or adsorbents, dyes, flavorings and sweeteners. The dragee cores are coated with concentrated sugar solutions, e.g. may still contain gum arabic, talc and / or titanium dioxide, or with a varnish which is dissolved in volatile organic solvents or solvent mixtures. Dyes may be added to these coatings, e.g. for labeling different doses of active substance.

Other oral unit dosage forms are gelatine capsules and soft, closed capsules of gelatin and a plasticizer, such as. Glycerol. The capsules contain the active substance. preferably as granules, e.g. in admixture with fillers, such as corn starch, and / or lubricants, such as talc or magnesium stearate, and optionally stabilizers, e.g. Ascorbic acid. In soft capsules, the active ingredient is preferably dissolved or suspended in suitable liquids, such as liquid polyethylene glycols, it also being possible for stabilizers to be added.

Suitable non-dosed dosage forms are, in particular, syrups which are prepared in a customary manner and which contain an active compound of the general formula I, preferably in suspended form.

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The pharmaceutical preparations may be sterilized and / or adjuvants, e.g. Preservatives, stabilizers, wetting agents and / or emulsifiers, solubilizers, salts for regulating the osmotic pressure and / or buffers. The present pharmaceutical compositions which, if desired, may contain other pharmacologically active substances, are prepared in a manner known per se, e.g. by means of conventional mixing, granulating, coating or dissolving processes, prepared and containing from about 5% to 100%, in particular from about 10% to about 80%, of one or more compounds of general formula I.

The process according to the invention is characterized in that a) a compound of the general formula II

(II)

in which Z is a halogen atom, with a compound of general formula III

H- / ^ ¹ (III)

or b) a compound of general formula IV -

(IV)

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in which R, R, X and X have the meaning given under formula I, with a lower alkyl mercaptan or an alkali metal lower alkyl mercaptide to give a compound of general formula I in which X or X_ is lower alkylthio, X "or X is hydrogen and Y and Y "together represent an additional bond and R, R, X and X have the meaning given under the formula I, or

c) in a compound of the formula

^X 2 / ^Y 2

-4. HI] f -X (V)

v \ / v

wherein Z is an etherified mercapto group and Z _{0 is} a group of the formula η = NR ₁ , E = NHR ₁ ] A ~ or C = N (R ₁ ) (R ₂ )] A, in which A ^ is an acid anion

is the Z -C (= Z) group hydrolyzed to the corresponding O = C (NR R) group and, if desired, a compound of general formula I, wherein X and X is lower alkoxy and Y and Y together represent an additional bond , to the corresponding compound, wherein X is hydroxy, or hydrolyzed to the tautomeric oxo compound and this optionally reduced to the corresponding compound with hydroxy X ₁ and hydrogen Y, X "and Y" or a compound of general formula I in which as X χ and X is lower alkylthio, oxidized to the corresponding compound of general formula I with lower alkylsulfonyl or lower alkylsulfinyl as X, X and / or X.

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The reaction according to a) is preferably carried out in an organic solvent, e.g. in a lower alkanol, such as ethanol, isopropanol or butanol, in an ethereal liquid, such as tetrahydrofuran or dioxane, or a hydrocarbon, such as benzene or toluene, at room temperature or, preferably, in the heat, e.g. at the boiling temperature of the solvent used, carried out. The ammonia and other gaseous starting materials of the general formula III which may be required as starting material may be introduced at the beginning or during the entire reaction time, or may also be used as concentrated aqueous solution when using a water-miscible solvent. But you can also use liquid ammonia or methylamine and perform the reaction if necessary in a closed vessel.

Starting materials of general formula II are obtained, for example, by reacting the corresponding 5-unsubstituted 5H-dibenz- [b, f] azepines with phosgene or carbonic acid dibromide in an inert organic solvent, such as e.g. Benzene or especially toluene, at room temperature or moderately elevated temperature, z ,. 3 .bis boiling temperature of the solvents mentioned. Of the 5H-dibenz [b, f] azepines required for this reaction, some are known and the others can be prepared in a manner known per se.

The. if desired, to the reaction according to a) subsequent hydrolysis of compounds with lower alkoxy as X or X according to the enol ether character of these compounds, for example by heating in an aqueous or aqueous organic mineral acid, eg in dilute eg 2-normal hydrochloric acid, or dilute sulfuric acid to massive elevated temperatures up to boiling temperature, ie about 60 to slightly above 100 ⁰ C. However, the hydrolysis can also eg in

  - 15 -

an aqueous-organic medium, for example a mixture of water with a lower alkanol or dioxane, in the presence of an acidic ion exchanger, eg Amber lite ^W IR-100 (trade name of Rohm and Haas, Philadelphia) or Dowex (trade name of Dow Chemical Co ., Midland, Michigan). '

The reaction according to b) is preferably carried out in the presence of an alkaline condensing agent, such as an alkali metal lower alkoxide, or the lower alkyl mercaptan is used in the form of an alkali metal mercaptide, for example sodium mercaptide. The reaction takes place, for example, in a lower alkanol, such as ethanol ₅ at room temperature to moderately elevated temperatures, for example up to 100 ° C. or boiling point of the solvent used. Of the starting materials of general formula IV is the la, 10b-dihydro-6H-dibenz- [b, f] oxireno [d] azepine-6-carboxamide known and others can be prepared analogously to this compound.

In reaction c), for example, compounds of formula V are used in which the etherified mercapto group Z is aliphatically etherified mercapto, such as lower alkylthio, e.g. Methylthio, and the acid anion A ^ *, for example, the anion of a strong protic acid, for example, a hydrohalic acid, such as a halide, e.g. the iodide ion, is. The hydrolysis is preferably carried out in an alkaline medium, e.g. in an aqueous alkali, such as soda or potassium hydroxide, preferably in the temperature range of about 60 to about 100 °, preferably carried out in the boiling heat.

The hydrolysis of lower alkoxy to hydroxy is e.g. by treatment with an aqueous mineral acid; the reduction of the double bond, which is also accessible to other compounds of formula I in which Y and Y "are a bond, by catalytic hydrogenation, e.g. in the presence of copper chromite. The oxidation of lower alkylthio to lower alkylsulfinyl or -sulfonyl takes place, for example, by means of hydrogen peroxide

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in a relative to this inert organic or organic aqueous solvent, for. B, in optionally water-containing acetic acid, or, in the resulting mixture of glacial acetic acid and aqueous Y / pererstoffperoxidlösung at moderately elevated temperatures between about 60 and 100 ⁰ G, if as oxidation product a substituted by lower alkylsulfonyl compound should be obtained. The oxidation of the / lower alkylthio to the Hiederalkylsulfiny! Group is z * B. either by the above method in the temperature range of about 20 to 60 G, or in particular using alkali metal, in particular sodium or potassium periodate, such as Hatriummetaperjodat in organic-aqueous, z , B. low alkanolic-aqueous, in particular ethanolic aqueous medium in the cold, z, B. carried out at 0 ⁰ G to room temperature, see also GB-PS T 114 970. The starting materials for these oxidations z, B. according to method a) or, if Σ. or is liederaikylthio, also be prepared according to process b).

The invention also relates to those embodiments of the process described, according to which one starts from a, available at any stage of the process as an intermediate compound and executes the missing process steps or forms a starting material under the reaction conditions or uses in Porm of a derivative. Preference is given to using those starting materials which lead to the novel compounds highlighted above, new starting materials and processes for their preparation likewise being a new subject of the invention.

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embodiment

In Examples 1 to 9 below, the Heratellang compounds according to the invention are described in more detail compounds of the general formula I and in the further examples the preparation of pharmaceutical preparations according to the invention, without in any way restricting the scope of the invention *

- 17 - -

Example 1 : 27.1 g (0.1 mol) of 3-methylsulfonyl-5H-dibenz [b, f] azepine are added with stirring to a solution of 19.8 g (0.2 mol) of phosgene in 300 ml of abs. Toluene registered. The mixture is refluxed for 20 hours. It is then evaporated on a rotary evaporator completely, leaving the crude 3-methylsulfonyl-5H-dibenz [b, f] azapine-5-carbonyl chloride of the mp. 160-162 ° remains.

The above crude product is dissolved with stirring at 70 ° in 600 ml of absolute ethanol. Ammonia gas is passed into this solution for 2 hours, during which the reaction solution is always boiled under reflux. The reaction mixture is then evaporated on a rotary evaporator, the residue is washed with water and the 3-methylsulfonyl-5H-dibenz [b, f] azepine-5-carboxamide is recrystallised after drying from acetonitrile *, mp 195-197 °.

The starting material can be prepared as follows:

a) To a solution of 27.3 g (0.1 mol) of 10, 11-dihydro-3-methylsulfonyl-5H-dibenz [b, f] azepine (see GB-PS 1,000,191) in 100 ml of toluene is allowed under Stir within 30 minutes 9g (0.115 moles) of acetyl chloride, keeping the temperature between 20 to 50 °. Subsequently, the reaction mixture is refluxed for 5 hours and then cooled to 5 °, whereupon the 5-acetyl-lO, dihydro-3-methylsulfonyl-5H-dibenz [b, f] azepine crystallized out. It is filtered off with suction, washed well with water and dried in a vacuum oven at 80 °, mp. Then 157-159 °.

b) 31.5 g (0.1, MoI) of 5-acetyl-10, 11-dihydro-3-methylsulfonyl-5H- ^i- dibenzo [b, f] azepine are dissolved in 2000 ml of carbon tetrachloride and the solution is 8 g (0.1 mol) of N-bromosuccinimide were added. Under stirring and in a nitrogen atmosphere, the mixture is heated to boiling under exposure to a UV lamp. The mixture is kept boiling until all the N-bromosuccinimide, which is at the bottom of the vessel. is converted to floating on the solution succinimide; what about

- 18 -

takes an hour. Then cool the reaction mixture to 20 ° and wash it in a separating funnel with water. After drying over sodium sulfate, the solvent is distilled off in a rotary evaporator and the oily residue dissolved in 60 ml of absolute ethanol. This solution is washed with a solution of 60 g of potassium hydroxide in 24.0 ml abs. Ethanol added and boiled under reflux for one hour. After cooling the reaction mixture to 20 ° 2000 ml of water are added, the precipitated crystals of 3-methylsulfonyl-5H-dibenz [b, flazepin are filtered off with suction, washed with water, then with diethyl ether and dried in a vacuum oven at 80 °; On this 141-143 °,

Example 2 : Analogously to Example 1, from 23.9 g (0.1 mol) of 3-methylthio-5H-dibenz [b, flazepine and 19.8 g (0.2 mol) of phosgene in 300 ml of abs. Toluene, the 3-methylthio-5H-dibenz [b, f] azepine-5-carbonyl chloride as an oily crude product and from it with ammonia gas in 600 ml of absolute ethanol, the 3-methylthio-5H-dibenz [b, f] azepine-5-carboxamide, Mp 179-180 ° (made from methanol.

The starting material is prepared analogously to Example la) and Ib);

a) From 24.1 g (0.1 mol) of 10, 11-dihydro-3-methylthio-5H-dibenz [b, f] -azepine (GB-PS 1,114,970) and 9 g (0.115 mol) of acetyl chloride in 100 ml Toluene gives the 5-acetyl-lO, l-dihydro-methylthio-SH-dibenz [b, flazepine, mp 69-74 ° (from petroleum ether).

b) From 28.3 g of 5-acetyl-3,10,11-dihydro-10,11-dihydro-3-methylthio-5H-dibenzo [b, fjazepine and 17.8 g (0.1 mol) of N-bromosuccinimide in 2000 ml of carbon tetrachloride and subsequent treatment with 60 g of potassium hydroxide in 300 ml of absolute ethanol, the 3-methylthio-5H-dibenz [b, flazepine, mp 167-169 ° (from ethanol).

EXAMPLE 3 Analogously to Example 1, 22.3 g (0.1 mol) of 3-methoxy-5H-dibenz [b, f] azepine and 19.8 g (0.2 mol) of phosgene are obtained.

- 19 -

in 300 ml of absolute toluene, the 3-methoxy-5H-dibenz [b, f] azepine-5-carbonyl chloride as an oily crude product and from this with ammonia gas in 600 ml of absolute ethanol, the 3-methoxy-5H-dibenz [b, f] azepine 5-carboxamide, mp 154-156 ° (from benzene).

The starting material is prepared analogously to Example la) and Ib) from the 10, 11-dihydro-3-methoxy-5H-dibenz [b, f] azepine (cf., British Patent 926,816) by acetylation, bromination and hydrogen bromide removal.

EXAMPLE 4 Analogously to Example 1, 30 g (0.1 mol) of 3- (dimethylsulfamoyl) -5H-dibenz [b, f] azepine (cf., CH-PS 408.92Z) and 19.8 g (0, 2 mol) of phosgene in 300 ml of absolute toluene, the 3- (dimethylsulfamoyl) -5H-dibenz [b, f] azepine-5-carbonyl chloride as an oily crude product and from it with ammonia gas in 600 ml of absolute ethanol, the 3- (dimethylsulfamoyl) -5H- dibenz [b, f] azepine-5-carboxamide, m.p. 215-217 ° (from methanol).

Example 5 : Analogously to Example 1, 21.8 g (0.1 mol) of 5H-dibenz- [b, f] azepine-3-carbonitrile and 19.8 g (0.2 mol) of phosgene in 300 ml of absolute toluene are obtained the 3-cyano-5H-dibenz (b, f] azepine-5-carbonyl chloride, mp 168-170 ° (crude product) 'and from it with ammonia gas in 600 ml of absolute ethanol, the 3-cyano-5H-dibenz [b, f ] azepine-5-carboxamide, m.p. 269-272 ° (from chloroform).

The starting material is prepared as follows:

a) Analogously to Example la) is obtained from 27.2 g (0.1 mol) of 3-bromo-lO, 11-dihydro-5H-dibenz [b, fjazepin and 9 g (0.115 mol) of acetyl chloride in 300 ml of absolute toluene the 5-Acetyl-3-bromo-10, ll-dihydro-5H-dibenz- [b, f] azepine (crude product), (see US Patent 3,056,774).

b) Analog Example Ib) are obtained from 31.4 g (0.1 mol) of 5-acetyl-3-bromo-10, 11-dihydro-5H-dibenzo [b, f] azepine (crude product) and 17 , 8 g

- 20 -

(0.1 mol) of N-bromosuccinimide in 350 ml of carbon tetrachloride and subsequent treatment with 60 g of potassium hydroxide in 300 ml of absolute ethanol, the 3-bromo-5H-dibenz ["b, f] azepine, mp. 218-220 ° (from toluene ).

c) 27.2 g (0.1 mol) of 3-bromo-5H-dibenzo [b, f] azepine, 10.7 g (0.12 mol) of copper cyanide and 50 ml of dimethylformamide are refluxed with stirring for 4 hours. Subsequently, the reaction mixture is cooled to 40 ° and stirred vigorously with 200 ml of a 50% aqueous Aethylendiaminlösung and 200 ml of methylene chloride. Then the organic phase is separated and the aqueous phase is extracted twice more with methylene chloride. The combined organic solutions are washed with water, dried over sodium sulfate and concentrated to a small volume, whereupon the 5H-dibenz [b, f] -azepin-3-carbonitrile, mp. 181-182 ° crystallized on cooling.

EXAMPLE 6 Analogously to Example 1, 21.8 g (0.1 mol) of 5H-dibenz [b, f] azepine-2-carbonitrile and 19.8 g (0.2 mol) of phosgene in 300 ml of absolute toluene are obtained 2-cyano-5H-dibenz [b, f] azepine-5-carbonyl chloride, mp 208-209 ° (tube product) and from this with ammonia gas in 600 ml of absolute ethanol the 2-cyano-5H-dibenz [b, f] azepine -5-carboxamide, mp. From 284 ° with decomposition (from methylene chloride).

The starting material is prepared as follows:

a) Analogously to Example la) is obtained from 27.2 g (0.1 mol) of 2-bromo-lO, 11-dihydro-5H-dibenz [b, fJazepin and 9 g of acetyl chloride in 300 ml of abs. Toluene, the 5-acetyl-2-bromo-10, ll-dihydro-5H-dibenzo [b, f] azepine, m.p. 136-142 ° (crude product).

b) Anaolg Example Ib) is obtained from 31.4 g (0.1 mol) of 5-acetyl-2-bromo-10, 11-dihydro-5H-dibenzo [b, f] azepine and 17.8 g (0, 1 mol) of N-bromosuccinimide in 350 ml of carbon tetrachloride and then

; Treatment with 60 g of potassium hydroxide in 300 ml of absolute ethanol, the 2-bromo-5H-dibenz [b, fjazepine, mp. 111-113 ° (from hexane).

_ 21 -

c) Analogously to Example 5c) is obtained from 27.2 g (0.1 mol) of 2-bromo-5H-dibenz [b, fjazepin, 10.7 g (0.12 mol) of copper cyanide and 50 ml of dimethylformamide, the 5H-dibenz [b, f] azepine-2-carbonitrile, mp 171-173 °, (from methylene chloride).

Example 7 : 25.6 g (0.1 mol) of 5H-dibenz [b, f] azepine-5-carbonyl chloride (cf., GB Patent 906,452) are dissolved with stirring at 70 ° in 600 ml of absolute ethanol. In this solution is introduced for 2 hours gaseous methylamine, the reaction solution is always boiled under reflux. Subsequently, the reaction mixture is evaporated in a rotary evaporator and the residue is stirred with water. The product is filtered off with suction, washed well with water and then dried in a vacuum oven at 70 °. After recrystallization from ethanol, the N-methyl-5H-dibenz [b, f] azepine-5-carboxamide, mp. 210-212 °.

Anaolger manner is obtained using 27.0 g (0.1 mol) of 10-methyl-5H-dibenz [b, f] azepine-5-carbonyl chloride (see CH-PS 403,767), the N, 10-dimethyl 5H-dibenz [b, f] azepine-5-carboxamide.

Example 8 11.5 g (0.5 mol) of sodium are dissolved in 2000 ml of abs. Ethanol dissolved with stirring. In this solution at 20-40 ° 24 g (0.5 mol) of gaseous methyl mercaptan are introduced. Subsequently, 25.1 g (0.1 mol) of la, 10b-dihydro-6H-dibenzo [b, f] oxireno [d] azepine-6-carboxamide (see DE-OS 2,246,842) are added and the mixture 1-2 Cooked under reflux for hours. Then the 'reaction mixture is evaporated in vacuo and the residue is stirred with 1500 ml of water and 300 ml of diethyl ether for 3 hours at 2-5 °. The suspension is sucked and washed with water and diethyl ether. The moist 10-methylthio-5H-dibenz [b, f] azepine-5-carboxamide is dried in vacuo at 80 ° and melts after recrystallization from methanol at 175-177 °.

- 22 -

Example 9 : 28.2 g '(0.1 mole) of 10-methylthio-5H-dibenzo [b, f] azepine-5-carboxamide, 100 ml of glacial acetic acid and 42 ml of 30% aqueous hydrogen peroxide solution are stirred for one hour Heated to 85 °. Then the reaction mixture is cooled to 5 °, whereby the 10-methylsulfonyl-5H-dibenz [b, f] azepine-5-carboxamide crystallized out. The product is filtered off with suction, washed with 2N-acetic acid, then with water and finally with acetone. After drying in a vacuum oven at 100 °, the substance melts at 275-278 ° with decomposition.

Example 10: 26.3 g (O ₅ l mol) of 10-trifluoromethyl-10, 11-dihydro-5H-dibenz [b, fJazepine are added with stirring to a solution of 19.8 g (0.2 mol) of phosgene in 350 ml ml of toluene. The mixture is heated under constant introduction of phosgene for 20 hours to reflux. The mixture is then evaporated to dryness on a rotary evaporator, 50 ml of petroleum ether / ether (2: 1) are added and cooled with stirring to 5 °. The crystallized 10-trifluoromethyl-10, 11-dihydro-5H-dibenzo [b, f] azepine-5-carbonyl chloride is then filtered off with suction and dried; Smp, 154-158 °.

The above product is dissolved with stirring at 70 ° in 400 ml of 95% ethanol. Ammonia gas is passed into this solution for 5 hours, with the reaction solution constantly being refluxed. Then the reaction mixture is evaporated on a rotary evaporator to dryness and the residue is stirred with water and a little ice-cold ether. The crystallized 10-trifluoromethyl-10, ll-dihydro-5H-dibenz [b ', f] -azepin-5-carboxamide is filtered off, washed with a little water and cold ether and dried:. Mp. 172-174 °.

The starting material may e.g. be prepared as follows:

a) 3.3 g (0.1 mol) of 10-bromo-5-acetyl-5H-dibenzo [b, fjazepine are autoclaved with 83.2 g (0.42 mol) of trifluoromethyl iodide and 31.6 g (0, 5 mol) of copper powder in 250 ml of dimethylformamide for 70 hours at 150 °. Then, 200 ml of dimethylformamide on a rotary evaporator

_ 23 _

distilled off and the residue extracted 4 times with 800 ml of ether. The combined ether extracts are washed 3 times with water and dried over sodium sulfate. After clarification with diatomaceous earth and carbon, the ethereal solution is concentrated to 50 ml and cooled to 5 °. The crystallized 10-trifluoromethyl-5-acetyl-5H-dibenz [b, fJaz.epin is suction filtered and dried; Mp 144-147 °.

b) 30.3 g (0.1 mol) of 10-trifluoromethyl-5-acetyl-5H-dibenz [b, fjazepine are dissolved in a solution of 30 g of potassium hydroxide pellets (85%) in 120 ml of ethanol with stirring for 2 hours to the. Reflux heated. The reaction mixture is then poured into 900 ml of water and extracted 3 times with 300 ml of ether. The combined ether extracts are washed twice with water and then dried over sodium sulfate. The solvent is distilled off in a rotary evaporator. The oily residue is dissolved in 90 ml of hexane and 10 ml of ether. The 10-trifluoromethyl-5H-dibenz [b, fjazepine crystallizes on cooling to 20 ° and is filtered off with suction and dried; Mp 123-126 °.

c) 26.1 g (0.1 mol) of 10-trifluoromethyl-5H-dibenz [b, fjäzepin be hydrogenated in 500 ml of ethyl acetate with 4.4 g of 10 Z Pd / C at 20-22 ° at atmospheric pressure for 40 hours. Then the catalyst is filtered off and the filtrate is evaporated in a rotary evaporator. The oily residue is purified by chromatography on 400 g of silica gel. The 10-trifluoromethyl-10, ll-dihydro-5H-dibenz [b, f] azepine is eluted with petroleum ether / toluene (4: 1); Mp. 57-59.

Example 11: Analogous to Example 1 turns off. 26.1 g (0.1 mol) of 10-trifluoromethyl-5H-dibenz [b, fjazepine and 19.8 g (0.2 mol) of phosgene in 350 ml of toluene, the 10-trifluoro-5H-dibenz [b, f] azepine-5-carbonyl chloride produced; Mp 140-144 °. This is also converted according to Example 1 with ammonia gas in 400 ml of ethanol in that of the 10-trifluoromethyl-5H-dibenz [b, f] azepine-5-carboxamide; Mp. 194-196 °.

- 24 -

Example 12: 28.2 g (0.1 mol) of 10-methylthio-5H-dibenzo [b, f] azepine-5-carboxamide are heated to reflux for 3 hours with 130 ml of 30 Z hydrogen peroxide in 600 ml of ethanol. Then the reaction mixture is evaporated to dryness in a rotary evaporator. The residue is dissolved in 100 ml of acetone and combined with 500 ml of absolute ether. The 10-methylsulfinyl-5H-dibenz [b, f] azepine-5-carboxamide is filtered off with suction and dried; Mp 242-247 °.

Example 13: In a manner analogous to that described in Examples 1-12, it is also possible to prepare:

10-Methoxy-ll-methyl-5H-dibenzo [b, f] azepine-5-carboxamide, 10-cyano-ll-methoxy-5H-dibenzo [b, f] azepine-5-carboxamide, 10-bromo-5H- dibenz [b, f] azepine-5 (N-methyl) carboxamide, 10-cyano-5H-dibenz [b, f] azepine-5 (N-methyl) carboxamide, 3,7-dichloro-10, 11-dihydro- 5H-dibenz [b, f] azepine-5-carboxamide, 3,7-dimethy1-10, 11-dihydro-5H-dibenz [b, f] azepine-5-carboxamide, 2,8-dimethy1-10, 11- dihydro-5H-dibenz [b, f] azepine-5-carboxamide, 3-methylthio-10, 11-dihydro-5H-dibenzo [b, f] azepine-5-carboxamide, 3-dimethylsulfamoyl-10, 11-dihydro- 5H-dibenz [b, f] azepine-5-carboxamide, 5 - [(1-piperidinyl) -carbonyl] -10, 11-dihydro-10-hydroxy-5H-dibenzo [b, f] -azepine,

5 - [(1-piperidinyl) carbonyl] -10,1l-dihydro-10-oxo-5H-dibenz [b, f] azepine,

3-methylsulfonyl-10, ll-dihydro-5H-dibenz [b, f] azepine-5-carboxamide.

- 25 -

Example 14; Tablets containing 25 mg each of 3-methylsulfonyl-5H-dibenz [b, f] azepine-5-carboxamide can be prepared as follows:

Composition (for 1000 tablets)

3-Methylsulfonyl-5H-dibenz [b, f] azepine-5-carboxamide 25.0 g

Lactose 250.0 g

Potato starch. 176.0 g

Gelatin 4.0 g

Talc 31.0 g

Magnesium stearate 5.0 g

Silica (highly dispersed), 10.0 g

Ethanol q.s.

The active ingredient is mixed with the lactose and 146 g of potato starch, the mixture is moistened with an alcoholic solution of gelatin and granulated through a sieve. After drying, the remainder of the potato starch, the talc, the magnesium stearate and the finely divided silicon dioxide are mixed in and pressed Mixture to tablets of each 73.0 mg in weight and the above-specified active ingredient content, which may optionally be provided with partial scores for finer adjustment of the dosage.

Instead of the above. Active ingredient may e.g. also the same amount of 10-methylthio-5H-dibenz [b, f] azepine-5-carboxamide can be used. :

In an analogous manner, it is also possible to prepare tablets containing another of the compounds of general formula I mentioned in the examples or specifically in the description.

Claims (27)

03/22/1984 -26- AP C 07 D / 255 64 7/3 63 046/11 Brf ind ungsans pr uoh 1, Process for the preparation of new 5H-dibenz / b, f7ase.pin-5-carboxamides of general formula I wherein R ₁ and EU are independently hydrogen or lower alkyl or lower alkyl or ethyleneoxyethylene, one of the symbols X .. and Xp is lower alkylthio ,. lower alkylsulfinyl, lower alkylsulfonyl, trifluorinatediyl, lower alkoxy, halogen of the atomic seminers to and / or cyano and the other hydrogen, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl or both symbols. and Σ are for .Wasserstoff, X ^ liiederalkyl, liedsraikoxy, Siederalkyithio, iiiederalkylsulfinyl, liederalkyl-.sulfonyl, trifluoromethyl, halogen and the Atomnunmer to 35 represents cyano or j Diniederalkylaulfamoyl or, if at least one of the best X and X ₂ is hydrogen ^Preferences is different and at the same time with halogen or cyano as X. or Xp and hydrogen as Xp or, X. R 'is hydrogen or lower alkyl and R _{2 is} lower alkyl or R ₁ together with R _{2 is} lower alkylene or Aethylenoxyäthylen and at the same time with liederaikoxy as X. X ₂ and hydrogen as Xp or · X R. together with Rp is lower alkylene or Aethylenoxyäthylen, may also be hydrogen, X, hydrogen -27- 22.3.1984 'AP G 07 D / 255 64 7/8 63 046/11 or at the same time, with -Hiaderalkyl or halogen as X- can also represent one of these radicals, and the symbols Y ₁ and Y ₂ , if one of the symbols X. and lower alkylthio, Miederalkylsulfinyl, Miederalkylsulfonyl or trifluoromethyl and. the other hydrogen or both represent hydrogen, each represents hydrogen .or if at least one of the radicals H ₁ , Rp, X ₁ and X ₂ of hydrogen or X- of cyano or at least one of X ₀ and X. of halogen together represent an additional bond, or wherein R ₁ and R ₂ together represent Hisderalkylen or .Aethylenoxyäthylen and X ₁ together with Y ₁ oxo and Xp and Yp is hydrogen or, X _{1 is} hydroxy and Xp, Y _{1 and} Y _{2 is} hydrogen represents or R and R _{9 are} independently or together Siiederalkyl Hiederalkylen or Aethylenosyäthylen. X 'or Bpiaethylen and Y ₁ and Y ₂ each' represents hydrogen, X., for hydrogen, lower alkyl, lower alkoxy, lower alkylthio, .... lower alkylsulf inyl, lower alkylsulfonyl _? 'Is trifluoromethyl, halogen of the atomic number to and with 35, cyano or di-lower alkylsulfamoyl, and X /' is hydrogen or at the same time also represents one of these radicals with lower alkyl or halogen as X-, characterized in that a) a compound of the general formula II  2 7a 22.3.1984 AP C 07 D / 255 64 7/8 63 046/11 Σ. \ I Γ / ^Ζ 2 Il Έ I GO-Z (ID ,. in which Z is a halogen atom, with a compound of general formula III H - Yes. • R, (my implements, or - 28 - b) a compound of general formula IV (IV) in which R, R_, X and X. the meaning given under formula I have been reacted with a lower alkyl mercaptan or an alkali metal lower alkyl mercaptide to give a compound of general formula I in which X or X is lower alkylthio, X or X is hydrogen and Y is and Y- together denote an additional bond and R, R, X and X have the meaning given under formula I, or c) in a compound of the formula ^X 1/2 ^X 2 / ^Y 2.
/ \ / \ / \ χ. -F ι * Γι 4-χ, (ν) ⁴ V \ / V M I -C C wherein Z is an etherified mercapto group and Z is a group of the formula η = NR ₁ ,. [-NHR ₁ ] ⁰ A ⁰ or [»NC ^ X ^)] © A ⁰ in which Α ^{Θ means} an acid anion, the Z - CC = Z ₃ ) group to the corresponding O = G (NR R) - -29- 22.3.1984 AP C 07 D / 255 64 7 / S 63 046/11 Group hydrolyzed and, if desired, a compound of general formula I, wherein G ₁ or »X ₂ Siederalkoxy. means and together represent Y ₁ and I ₂ an additional bond, to the corresponding compound wherein X ₁ is hydroxy, or hydrolyzed to the tautomeric oxo compound and this reduces, if desired, to the corresponding compound having hydroxyl X ₁ and hydrogen, Y _1, X ₂ and Y ₂ or a compound of general formula I in which as X ₁ , Xp. and / or X_ lower alkylthio; is oxidized to the corresponding compound of general formula I with Hiederalkylsulfonyl or liederalkylsulfinyl as X ₁ , X ₂ and / or X, 2. Method according to item 1 for the preparation of new 5H-dibenz £ b, f7-azepine-5-carboxamides of general formula I. (D, wherein R. and R _{2 are} independently hydrogen or Uie.deralkyl or joined together lower alkylene or ethyleneoxyethylene, one of the two symbols X. and X-. and / or the symbol X-lower alkylthio,! lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl and X-. also denotes kaogen to azo number 35, di-lower alkylsulfamoyl, lower-alkyl, cyano or lower alkoxy and the or the two remaining symbols X ₁ , X and X "denote hydrogen, but X ₁ or X ₂ , if at least one of the radicals R ₁  -30- 22.3 * 1984 AP C 07 D / 255 647 / 8-63 046/11 and R _{2 is} hydrogen and lower alkyl or one of X and X is other than hydrogen, and Y ₂ and Y _{2 are} an additional bond, also lower alkyl and X _? or, X. may be hydrogen, X. is hydrogen or, together with halogen or lower alkyl as X "may also represent one of these radicals, I. and I ₂ together represent an additional bond or at the same time with hydrogen as X. and Xp also ever May be hydrogen, or if at least one of R.sup.1 and R.sup.p is other than hydrogen and X, and X are hydrogen, X. also halogen to Atomnuinmer oder.Cyano, X _{2 is} hydrogen and I. and I ₂ together an additional Binding meaning A, characterized in that one. a) a compound of the general formula II (II) in which Z is a halogen atom, with a compound of general formula III U. (III) implements, or -31- '22.3.1984 AP G 07 D / 255 64 7/8 63 046/11 b) exna compound of the general formula IY H H - Ii IJ Jr- X ₃ Civ), IT CO-U ^R 2 in soft R., R ₀ , X ~, and X, which are under J. 1-1 c-3 4 , have meaning with a liederalkylaeroaptan or an alkali metal NiederalkyLnercaptid au a compound of general i'orinel Γ in which X ₁ or X _? Lower alkylthio, "Xp or, Σ. ..Hydrogen and Y. and Y ₀ together represent an additional formation and R., R ₂ , X-, and X- have the meaning given under the formula I, reacting and, if desired, a compound of general formula I, in which as X., X ₂ and / or X ~ is lower alkylthio, to the corresponding compound of general formula I with Hiederalkylsulfonyl or Miederalkylsulfinyl as X _H , Z ₀ and / or Z ~ oxydiert. 3, process according to point 2, characterized in that one produces compounds of the general formula I, wherein X "of cyano and R. and / or R ₂ of hydrogen or at least one of the radicals X" and X. is different from halogen, when X ₁ and Χ- are hydrogen and Υ _Λ and Y _{0 are} an additional bond. - ^: , -32- 22.3.1984 AP C 07 D / 255 64 7/3 63 046/11 4. The method according to item 1, characterized -dadurch., Characterized in that one of the two symbols X. and I ^ lower alkylthio, compounds of the general formula I, wherein R. and Rp are independently hydrogen or lower alkyl or lower alkylene or Äethylenoxyäthylen connected together, Lower alkylsulfinyl, lower alkylsulfonyl or trifluoromethyl and the other is hydrogen, X is hydrogen, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano, halogen up to atomic number 35, di-lower alkylsulfamoyl, lower alkyl or lower alkoxy, X, hydrogen or at the same time as halogen or lower alkyl as X- may also represent one of these radicals and Y ₁ and Yp together represent an additional bond or each hydrogen, produces » 5. The method according to any one of items 1 to 3, characterized in that compounds of the general formula I wherein R. and Rp are independently lower alkyl Wasserstoff.oder wheels connected among themselves or lower alkylene Aethylenoxyäthyien, X _-. and Xp is hydrogen, X "is halogen of the atomic number to and with 35, lower alkyl, lower alkoxy, lower alkylthio, lower alkylsulfinyl, lower alkylsulfonyl, trifluoromethyl, cyano or di-lower alkylsulfamoyl, X _{4 is} hydrogen or at the same time and Y. and Yp are each hydrogen or, if at least one of the radicals R. and R _? of hydrogen or X " of cyano or Σ. other than halogen, together constitute an additional bond, 6. Method according to one of the items 1 to. 3, characterized in that compounds of general formula I, -33- 22.3.1984 AP G 07 D / 255 64 7/3 63 046/11 wherein one of the symbols R ₁ and R _{2 is} lower alkyl and the other hydrogen or both for lower alkyl or together for lower alkylene or. Aethylenoxyäthylen stand, one of the symbols X .. and Xp halogen of the atomic number to and with 35 or cyano and the other as well as Z ~ and X, are hydrogen, wherein Y. 'and Yp together represent an additional bond, manufactures « 7. A process according to any one of items 1 to 3, characterized by reacting compounds of general formula I wherein R-. and R ₂ independently of one another represent hydrogen or lower alkyl or, connected to one another, are lower alkylene or ethyleneoxyethylene, X. and Y ₁ together are oxo. and Xp and Yp are each hydrogen. X is lower alkoxy or hydroxy and Xp, Y. and Yp are each hydrogen, X.sup.- is halogen atom number up to and including 35, lower alkyl, lower alkoxy, further lower alkylthio, lower alkyl / alkyl-3-fluoro, lower alkylsulphonyl, 1-rifluoromethyl, cyano or lower alkylsulphamoyl or if R.. and R ^ together represent lower alkylene or Ä. Aethylenoxyäthylen, is hydrogen and X _{4 is} hydrogen or at the same time with halogen or lower alkyl as X-, also one of these radicals, prepared 3. The method according to item 1, characterized by reacting compounds of the general formula I, wherein E ,, R ₂ , X. and Xp are hydrogen, X- Riederalkylthio, or lower alkylsulfinyl each having up to 4 carbon atoms, ^ lower alkylsulfamoyl having up to and including 4 C atoms in each alkyl part, lower alkyl or lower alkoxy having up to and including 4 C atoms, halogen of the atomic number up to and including 35 or trifluoromethyl, X.sup.4 is hydrogen or at the same time as lower alkyl or   -34- 22.3.1984 AP G 07 D / 255 64 7/8 63 046/11 Halogen as X_ can also be lower alkyl and Y ₁ and Yp in each case represent hydrogen or together form an additional bond, produces » 9. The method according to item 1, characterized in that one represents compounds of general formula I, wherein R. and R _{2 are} independently hydrogen or lower alkyl, each having and having 4 carbon atoms, one of the radicals X. and X ₂ Lower alkylthio, lower alkylsulphinyl or lower alkylsulphonyl having in each case up to and including 4 C atoms or trifluoromethyl or, if at least one of R, and R _{2 represents} lower alkyl, halogen of atomic number to and 35, or cyano and the other and X ' and. X. is hydrogen and Y. and Y. together represent an additional bond, produces » 10. The method according to item 1, characterized by reacting compounds of the general formula I, wherein 5 'of the symbols R ₁ , Rp, X ₁ ,' Xp, X .. and I. represent hydrogen and one of them different- radical R- , and / or R "liiedsralkyl with up to and with 4 C-atoms, one of which is different radical X ₁ or X ₂ lower alkylthio, Niederalkylsuifinyl or lower alkylsulfonyl with in each case to and 4 C atoms or irifluoromethyl or, one of which is different radical X ^ lower alkylthio, lower alkylaulphinyl or lower alkylsulphonyl having in each case up to and including 4 C atoms, dilithioalkylsulfamoyl having bis and. containing 4 C atoms in each alkyl, lower alkyl or lower alkoxy having up to and including 4 / C atoms, halogen of the 'atomic number up to and including 35 or tri-fluoromethyl and Y. and Y ₂ together constitute an additional bond. ' 11. A process according to any one of items 1 to 3, characterized in that 3-methylsulfonyl-5H-dibene / b, f7azepine-5-carboxamide is heard. -35- 22.3.1934 .AP G 07 D / 255 64 7/3 63 046/11 12. Method according to one of the items 1 to 3? characterized in that 3-methylthio-5H-d-benzene / b, f7azepLn-5-carboxamide is prepared. 13. Method according to one of. Points 1 to 3 _5, characterized in that 3-methoxy-5H-dibenz / b, f7azepin-5-carboramid produces. 14. Process according to one of the items 1 to 3, characterized in that 3- (dimethylsulfamoyl) -5H-dibenz / b, f7a2-capo-5-caiO2: amide is prepared » 15. Process according to one of the items 1 to 3 », characterized in that 3 - ^. Yano-5H-dibenz _J / b ', f7azepin-5-carboxaiiiid be prepared. " 16. Method according to one of the items 1 to 3 »gekennzelehnet in that 2-Gyano-5H-dibenz / b _> f7azepln-5-carboxamide produced * 17. The method according to any one of the items 1 to 3 »characterized in that one prepares li-methyl-5H-dibenz / b, f7azepin-5-carboxamide. 13. The method according to any one of items 1 to 3, characterized in that one prepares H, 1O-dimethyl-5H-dibenz / 'b, f7azepin-5-carbosamide,' - · .. 19. Method according to one of the items 1 to 3, characterized characterized in that iO-methylthio-5H-dibenz / b, f7azepln.-; 5-carboxamide produces. ' -36- 22 * 3.1984 AP G 07 D / 255 64 7/8 63 046/11 20, 'process according to one of the items 1 to 3, characterized in that 10-methylsulfonyl-5H-dibsnz_ / b, f7azepin-5-carboramid produces » Method according to item 1, characterized in that 10-trifluoromethyl-5H-dibenz / b, f7azepine-5-carbo2ainide is prepared * Method according to item 1, characterized in that 10-trifluoromethyl-10.1 1-dihydro-5H-diboride, ifb, i7azepine-5-carboramide is prepared * 23. Method according to item 1, characterized in that lO-methoxy-H-niethj-l-SH-dibenz / bjfyazepine-S-carbosamide is produced « 24. The method according to item 1, characterized in that 10-cyano-5H-dibenz / b, ^ 7azepin-5- (l ^, I-niethyl) carbosamide. manufactures. , Method according to item 1, characterized in that 3, 7-bichloro-IQ, 1 1-dihydro-5H-dibenz-1-b, jr / azep; Ln-5-carboxamide are prepared. 26. The method according to item 1, characterized in that one prepares 3, "-Dimethyl-10,11-dihydro-5H-dibenz / ^ 'b, f7 ^aae pi ^jrl ""5-carbozamide. 27. Method according to item 1, characterized in that 2, S-dimethyl-10,11-dihydro-5H-dibenz / "b, f7azepine-5-carboxamide is produced, 23 «method according to item 1, characterized in that one produces 3-methylthic-10,11-dihydro-5H-dibenz / b, f_7azepin-5-carbosamide. 03/22/1934 AP C 07 D / 255 64 7/3 63 046/11 29. The method according to item 1, characterized by preparing 3-dimethylsulfamoyl-10,11-dihydro-5H-dibenz / b, f7azepin-5-carboxamide. 30, method according to item 1, characterized in that 10-Methj / lsulf inyl-SH-dibenZj / bjfJazepin-S-car boramide
establishes " 31 «A method according to item 1, characterized in that 3- ^c hlor-5H-dibenz / b, f7azepin ~ 5-carboxamide produces" 32. The method according to item 1, characterized in that one produces 5- / Ti-piperidinyl) -carbonyj.7-iO, 11-dihydro-10-oxo-5H-dibenz / b, f_7-azepine. 33. The method according to item 1, characterized in that 5- / Ti-piperidinyl) carbonyl.7-10,11-dihydro-10-ft.ydr oxy- ^ zepin manufactures » 34. The method according to item 1, characterized in that 3-methylsulfonyl-10,11-dihydro-5H-dibenz / b ", f_7azepin-5-carboxamide produced. 35ο Method according to item 1, characterized in that IQ-gyano-11-metho3: y-5H-dibenz / _i ¥, f7azepin-5-carboxamide
manufactures ... '