EP1720827A1

EP1720827A1 - Method of preparing benzazepines and derivatives thereof

Info

Publication number: EP1720827A1
Application number: EP05728103A
Authority: EP
Inventors: Samir Zard; Alejandro Cordero Vargas; Béatrice SIRE
Original assignee: Centre National de la Recherche Scientifique CNRS; Ecole Polytechnique
Current assignee: Centre National de la Recherche Scientifique CNRS; Ecole Polytechnique
Priority date: 2004-03-02
Filing date: 2005-02-21
Publication date: 2006-11-15
Also published as: FR2867187B1; US20070185323A1; FR2867187A1; CA2557731A1; IL177649A0; JP2007526288A; WO2005085183A1

Abstract

The invention relates to a method of preparing benzazepine compounds having general formula (IA) consisting in reacting at least one compound having general formula (IIA) with an olefin, the compound thus obtained then being cyclised such as to produce tetralone, followed by the oxime derivative of same, which, by transformation by a Beckmann rearrangement, gives rise to the desired compounds.

Description

Process useful for the preparation of benzazepines and derivatives thereof The present invention aims more particularly to propose a new access route to molecules of the benzazepine type. Benzazepines and related molecules such as benzazepinones and benzodiazepines constitute families of compounds of interest for their pharmacological activities. Recently, it has thus been shown that two N-substituted benzazepine derivatives, namely (±) -N- [4- (7-c oro-5-hydroxy-2,3,4,5-térahydro-1H-lberιzazépin- l- ylcarbonyl) -3-methyl phenyl] -2-methylbenzamide (OPC-41061) and (±) -N- [4- (7-chloro- 5-hy <koxy-2,3A5-té1xahydro-1H-lbenzazépm -l-ylcarbonyl) - phenyl] -2-methylbenzamide (OPC-31260) from the company OTSUKA PHARMACEUTICALS could act as powerful antagonists of the V ₂ receptor for Arginine Vasopressin (AVP) and therefore be effectively used for the treatment of disorders heart. However, the various modes of synthesis currently available for obtaining these benzazepine derivatives constitute a major obstacle on the one hand, to obtain these compounds under satisfactory conditions in terms of yield and cost and on the other hand, for the development of new derivatives . Thus, the process, represented in FIG. 1, which corresponds to the synthetic route currently used to obtain the OPC-41061 derivative, comprises eleven consecutive steps, some of which involve drastic conditions which are not compatible with the presence of a certain number of functional groups. . The object of the present invention is precisely to propose a new access route to benzazepine type compounds, advantageously allowing, on the one hand, the preparation of known compounds under satisfactory conditions and, on the other hand, access to new derivatives. of these compounds.

More precisely, the present invention relates, according to a first of its aspects, to a process for the preparation of at least one benzazepine compound of general formula (TA): in which :

- R ¹ represents a halogen atom chosen from chlorine, fluorine, bromine and iodine, an al yl, haloalkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl group, or else a hydrocarbon ring or a heterocycle, a polymer chain, a group - <CH ₂ ) _m -OR, -CHCOR ^ COR ¹ ), - (CH ₂ ) _m -SR, - (CH ₂ ) _m -S (O) R ^k , - (CH ₂ ) _m -SO ₂ R ^k , - (CH ₂ ) _m -SO ₂ NR ^k R ¹ , - (CH ₂ ) _m -SO ₃ R ^k , - (CH ₂ ) _m -NO ₂ , - (CH ₂ ) _m -CN, - (CH ₂ ) _m -PO (OR ^k ) (OR ¹ ), - (Clfc) _n rSiR ^k R ^{1 m} , - (CH ₂ ) _m -COOR ^k , - (CH ₂ ) _m - NCOR ^k , - (CHs -N ^ ¹ , with: R ^k , R ¹ and R ^m each independently denoting a hydrogen atom, an alkyl, haloalkyl, acyl, aryl, alkenyl, arylalkenyl, alkynyl, arylalkynyl group , aralkyl, alkaryl, a hydrocarbon ring or a heterocycle, or else R ^k and R ¹ form together with the atom to which they are attached a heterocycle, with m denoting an integer greater than or equal to 0, in particular ranging from 0 to 100, and in particular ranging from 0 to 20,

- n represents an integer chosen from 0, 1, 2, 3 and 4, with when n is greater than or equal to 2, the corresponding groups R ¹ can be identical or different, and if necessary can together form a hydrocarbon ring or a heterocycle, for example with 5 or 6 links.

- R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ independently represent one of the other a hydrogen atom, a halogen atom chosen from chlorine, fluorine and bromine, an alkyl, haloalkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl group, or a hydrocarbon ring or a heterocycle, a polymer chain, a group - (CH ₂ ) _m -OR ^k , -CH (OR ^k ) (OR ¹ ), - (CH ₂ ) _m -SR ^k , - (CH ₂ ) _ffi -S (O) R ^k , - (CH ₂ ) _m -SO ₂ R ^k , - (CH ₂ ) _m -SO ₂ NR ^k R ¹ , - (CH ₂ ) _m -SO ₃ R ^k , - (CH ₂ ) _m -NO ₂ , - (CH ₂ ) _m -CN, - (CH ₂ ) _m -PO (OR ^k ) ( ORj, - (Œb) _m -SiR ^fc R ^I R ^m , - (CH ₂ ) _m -COOR ^k , - (CH ₂ ) _m - NCOR ^k , - (CH ₂ ) _m - R ^k R ¹ , with R ^k , R ¹ , R ^m and m as defined above, or R ⁴ , R ⁵ , R ⁶ and R ⁷ form one by two one or more hydrocarbon (s) or heterocycle (s) rings, with at least one of the groups R ⁴ , R ⁵ , R ⁶ and R ⁷ representing a hydrogen atom, from at least one compound of general formula (IIA)

in which

Z ¹ represents a group chosen from: (i) alkyl, acyl, aryl, aralkyl, alkene or alkyne groups, hydrocarbon rings or heterocycles, (ii) a group -OR ^a or -SR ^a in which R ^a is a group chosen from: - an alkyl, haloalkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl group, or else a hydrocarbon ring or a heterocycle, or else a polymer chain; a group -CR ^b R ° PO (OR ^d ) (OR ^e ) in which: • R ^b and R ^c each represent, independently of one another, a hydrogen atom, a halogen atom, an alkyl or perfluoroalkyl group, a hydrocarbon ring or a heterocycle, or alternatively a group -NO ₂ , -NCO, -CN, or a group chosen from groups of type -R ^f , -SO ₃ R ^f , - OR ^f , -SR ^f , -NR ^f R ⁸ , -COOR, -O ₂ CR ^f , -CO R ^f R ⁸ , -NR ^ QR ⁸ , in which R and R ^ë each independently denote an alkyl group, alkenyl, alkynyl, cycloalkenyl, cycloalkynyl, aryl optionally condensed with a heterocycle, alkaryl, arylalkyl, heteroaryl, • or else R ^b and R ° together form with the carbon atom to which they are attached a group C = O or C = S or else a hydrocarbon cycle or a heterocycle; and • R ^d and R ^e each represent, independently of one another, a radical corresponding to one of the definitions given above for the group R ^f ; • or else R ^d and R ^e together form a hydrocarbon chain comprising from 2 to 4 carbon atoms, possibly interrupted by a chosen group from -O-, -S- and-NR ^h -; where R ^h meets one of the definitions given above for the group R ^f ; (ϋi) a group -NR'R ¹ , in which: - R ¹ and R ^j , independently represent one of the other a radical chosen from an alkyl, haloalkyl, alkenyl, alkynyl, acyl, ester, aryl group , arylalkyl, arylalkenyl, arylalkynyl, or alternatively a hydrocarbon ring or a heterocycle; or - R ¹ and R. together form a hydrocarbon chain, comprising from 2 to 4 carbon atoms, optionally interrupted by a group -O-, -S-, or -NR ^h -, where R ^h corresponds to one of definitions given above for the group R ^f , (said hydrocarbon chain advantageously forming a 5-membered ring with the nitrogen atom to which R ¹ and R ^j are attached),

R ^2a represents a group chosen from a hydrogen atom, a halogen atom, in particular fluorine, chlorine or bromine, an alkyl, haloalkyl, acyl, aryl, arylalkyl group, or else a hydrocarbon ring or a heterocycle, a polymer chain, a group - (CH ₂ ) _m -OR ^k , -CH OR ^k ) (OR ¹ ), - (CH ₂ ) _m -SR ^k , - (CH ₂ ) _m -S (O) R ^k , - (CH ₂ ) _m - SO ₂ R, - (CH ₂ ) _m -SO ₂ NR ^k R ¹ , - (CH ₂ ) _m -SO ₃ R, - (CH ₂ ) _m -NO ₂ , - (CH ₂ ) _m -CN, - (CH ₂ ) _m - - (CH ₂ ) _m -COOR, - (CH ₂ ) _m -NCOR ^k , - (CH ₂ ) _m -NR ^k R ¹ , in which R ^k , R ¹ , R ^m and m are as defined above and preferably a hydrogen atom,

- R ¹ and n are as defined above, comprising at least the steps consisting in: a- reacting said compound of general formula (HA) with at least one olefin of general formula (A) in which :

R ⁴ , R ⁵ , R ⁶ and R ⁷ are as defined above, with at least one of the groups R ⁴ , R ⁵ , R ⁶ or R ⁷ representing a hydrogen atom, to obtain at least one compound of general formula (IIIA) in which :

R ¹ , R ^2a , R ⁴ , R ⁵ , R ⁶ , R ⁷ , Z ¹ and n are as defined above, b- radicalizing said compound of general formula (IHA) to obtain at least one compound tetralone of general formula (INA)

in which :

R ¹ , R ^2a , R ⁴ , R ⁵ , R ⁶ , R ⁷ and n are as defined above, c- transforming said compound of general formula (INA) into at least its oxime derivative of general formula (VA)

in which :

R ¹ , R ^2a , R ⁴ , R ⁵ , R ⁶ , R ⁷ and n are as defined above, d- transforming said compound of general formula (VA) by a Beckmann rearrangement and consecutive reduction (s) ( s) in at least one compound of general formula (IA), and e- recovering said compound of general formula (IA). According to another of its aspects, the invention also relates to a process for the preparation of at least one compound of general formula (EB)

in which :

R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and n are as defined above, X represents O, R ⁹ , S, S (O), SO ₂ , SO ₂ NR ⁹ and

R ⁸ and R ⁹ independently of one another represent a hydrogen atom, an alkyl, haloalkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, alkaryl, arylalkenyl, arylalkynyl group, or a hydrocarbon ring or a heterocycle , a polymer chain, optionally substituted, or else R ⁸ and R ⁹ form, together with the atom to which they are attached, a heterocycle, starting from at least one compound of general formula (TVB)

in which: R ¹ , R ⁴ , R ⁵ , R ⁶ , R ⁸ , X and n are as defined above, and R ^2a is as defined above, comprising at least the steps consisting in: a ' transforming said compound of general formula (IVB) into at least its oxime derivative of general formula (VB)

in which :

R ¹ , R, R ⁴ , R ⁵ , R ⁶ , R ⁸ , X and n are as defined above. b'- transforming said compound of general formula (VB) by Beckmann rearrangement and subsequent reduction (s) into at least said compound of general formula (TB), and c'- recovering said compound of general formula (IB) .

Throughout the present description, the term “alkyl group” is intended to cover a saturated, linear or branched hydrocarbon radical, which may optionally include one or more saturated aliphatic ring (s). Within the meaning of the invention, the alkyl groups can have up to 25 carbon atoms, in particular from 1 to 12 carbon atoms, and in particular from 1 to 6 carbon atoms. Mention may in particular be made, among the alkyl radicals, of the methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, pentyl, hexyl, octyl, decyl or dodecyl radical. In particular, an alkyl group may also denote, within the meaning of the present description, a cycloalkyl group, that is to say a cyclic saturated hydrocarbon radical, having in particular from 3 to 10 carbon atoms. For its part, an "alkoxy" group denotes, within the meaning of the present description, a radical -OAlk, where Alk denotes an alkyl group as defined above. By “haloalkyl” group within the meaning of the present description, is meant an alkyl radical as defined above and substituted by at least one halogen atom, where the term “halogen atom” designates here, as in all of the description, a fluorine, chlorine, bromine or iodine atom, in particular a fluorine or chlorine atom. The "haloalkyl" groups of the invention can thus be, for example, "perfluoroalkyl" groups, that is to say, within the meaning of the invention, groups corresponding to the formula -CH_C_T__ ₊ ι, where n represents an integer ranging from 1 to 20. By "alkenyl" group, in the sense in which it is used in the present description, is intended to denote an unsaturated, linear or branched hydrocarbon-based radical having at least one C = C double bond. The alkenyl groups of the invention can have from 2 to 25 carbon atoms, in particular from 2 to 12 carbon atoms, and in particular from 2 to 6 carbon atoms. Likewise, the term "alkynyl" is intended to mean an unsaturated, linear or branched hydrocarbon-based radical having at least one C tripleC triple bond. The alkynyl groups of the invention generally have from 2 to 25 carbon atoms, in particular from 2 to 15 carbon atoms, and in particular from 2 to 6 carbon atoms. By "ester" and "acyl" group within the meaning of the present description, is meant respectively a group -C (= O) -OB, and -C (= O) -B where B denotes a saturated linear or branched hydrocarbon chain or unsaturated, and comprising from 1 to 25 carbon atoms, and which can in particular be an alkyl, alkenyl or alkynyl group as defined above. Within the meaning of the present description, a radical of “hydrocarbon ring” type designates a saturated, unsaturated or aromatic cyclic group, in particular of cycloalkyl, cycloalkenyl or cycloalkynyl type, optionally substituted, and comprising from 3 to 20 carbon atoms. A “heterocycle” type radical designates such a carbon ring interrupted by at least one heteroatom chosen for example from N, O, S, P and Si, said carbon ring being able to be saturated or iπsa-urea. An "aryl" group, for its part, denotes, within the meaning of the present description, a mono- or poly-cyclic aromatic group generally having from 5 to 20 carbon atoms, and in particular from 6 to 10 carbon atoms. Thus, it may for example be a phenyl group, or alternatively 1- or 2-naphthyl. According to a particular variant, an "aryl" group within the meaning of the invention can integrate one or more heteroatoms such as sulfur, oxygen, or nitrogen. In this particular case, the group "aryl" denotes a heteroaromatic group mono- or polycyclic. The “arylalkyl”, “aralkenyl” and “aralkynyl” groups within the meaning of the present description are respectively alkyl, alkenyl and alkynyl chains substituted by an aryl group as defined above. The different radicals can optionally be interrupted by one or more heteroatoms chosen in particular from O, S, N, P and Si, or by groups - (C = O) -, - (C = S) -, -SO ₂ -, -SO-, or secondary or tertiary amines, and they may be substituted by any type of group which is not capable of interfering with the reaction under consideration or of leading to parasitic reactions between the compounds present, and in particular by one or more identical or different groups chosen from alkoxycarbonyl or aryloxycarbonyl (-COOR), carboxy (-COOH), acyloxy (-O2CR), carbamoyl (-CONR ₂ ), cyano (-CN), alkylcarbonyl, alkylarylcarbonyl, arylcarbonyl, arylalkylcarbonyl, phthalimido, maleimido, succinimido, amidino, guanidino, hydroxy (-OH), amino (-NR ₂ ) or (-NH ₂ ), halogen, perfluoroalkyl (C_T? __ ₊ _), allyl, epoxy, alkoxy ( -OR), thioalkoxy or thioaryloxy (-SR), sulfones, phosphonates, a silyl group, a halogen atom, groups having a hydrophilic or ionic character such as the alkali salts of carboxylic acids, the alkali salts of acids sulfonic or phosphonic, polyalkylene oxide chains (POP, POE), cationic substituents (quaternary ammonium salts), R representing an alkyl or aryl group, or a polymer chain, said substituents possibly being interrupted by heteroatoms. It is the skill of a person skilled in the art to choose the nature of the different groups and substituents present in the compounds used to avoid any undesirable side reaction.

The methods according to the invention are particularly advantageous for preparing benzazepine compounds corresponding to the general formula (LA) or (IB) in which n = 1, and in particular in which R ¹ is in the para position (relative to the atom nitrogen). The group R ¹ may represent a halogen atom, in particular fluorine, chlorine, bromine or iodine, or an alkoxy group, in particular methoxy. According to a variant of the invention, the benzazepine compound can correspond to the formula (LA) or (EB) in which R ² and R ³ each independently represent a hydrogen atom, or an alkyl group. According to another variant of the invention, the benzazepine compound can correspond to the general formula (IA) or (IB) in which R ² and R ³ each represent a halogen atom, and in particular of chlorine, fluorine or bromine .

Among the compounds of general formula (IIA) which can be used in step a- of the process constituting the first aspect of the invention, mention may be made in particular of xanthatic compounds, that is to say in which Z ¹ represents -OR ^a and in particular those in which R ^a represents a C 1 to C ₂ alkyl group, and in particular an ethyl group. As regards the tolefine of formula (A), it can be mono- or di-substituted. In the case of disubstituted olefins, they may be cyclic olefins, for example cyclopentene or norbornene, with in this case either R ⁴ and R ⁷ or R ⁶ and R ⁵ each representing an atom d hydrogen, or terminal disubstituted olefins, that is to say with either R ⁴ and R ⁵ , or R ⁷ and R ⁶ each representing a hydrogen atom. In this case, the benzazepines according to the invention correspond to the general formula (LA) or (IB) in which at least two of the substituents R ⁴ , R ⁵ , R ⁶ and R ⁷ , and in particular either R ⁴ and R ⁵ , either R ⁷ and R ⁶ , or alternatively either R ⁴ and R ⁷ , or R ⁶ and R ⁵ each represent a hydrogen atom. According to a particular variant of the invention, the olefin is monosubstituted. Thus very particularly suitable for the invention, the olefins of formula (A) in which R ⁴ , R ⁵ and R ⁶ simultaneously represent a hydrogen atom and in particular those in which R ⁷ represents a group -XR ⁸ as defined above. More particularly, the benzazepines according to the invention correspond to the general formula (LA) or (IB) in which R ⁴ , R ⁵ and R ⁶ simultaneously represent a hydrogen atom. The substituent (s) of this olefin can be chosen from -O acyl groups and groups of type - (CH 2) _P CN, with p representing an integer varying from 1 to 10, and in particular equal to 1. Illustrative of the olefins of formula (A) capable of being used according to the invention, there may be mentioned in particular: - vinyl pivalate, allyl cyanide, and N-vinyl phthalimide. This olefin is generally placed in the presence of the compound of formula (HA) in step a, in a molar ratio at least equal to 1, in particular greater than or equal to 1.5. Generally, the two compounds are brought into contact in a form soluble in an organic solvent. Steps a and b are generally carried out by radical route. In particular, the compounds of formula (HA) and / or (TUA) can undergo a photochemical activation, in particular by exposure to light and / or chemical, for example by decomposition of a peroxide, such as dilauryl peroxide or a diazo compound (thermal decomposition) or decomposition by autooxidation with oxygen of an organometallic compound such as triethylborane, diethylzinc, a trialkylaluminium. As an example of peroxides which are particularly suitable as a source of free radicals in the process of the invention, mention may in particular be made of diisobutyryl peroxide, cumyl peroxynodeodecanoate, tert-amyl peroxynodecanoate, di (2-ethylhexyl) peroxydicarbonate, peroxynodecanoate tert-butyl, dibutyl peroxydicarbonate, diketyl peroxydicarbonate, dimyristyl peroxydicarbonate, tert-butyl peroxynoheptanoate, tert-amyl peroxypivalate, didecanoyl peroxide, tert-amyl peroxy-2-ethylhexanoate, tert-butyl peroxyisobutyrate , 4-di (tert-butylperoxycarbo) cyclohexane, tert-butyl peroxyacetate, tert-butyl peroxybenzoate, di-tert-amyl peroxide, tert-butyl cumyl peroxide, bis-tertiobutyl peroxide, dicumyl peroxide, dilauroyl peroxide (DLP) or di (4-tert-butylcyclohexyl) peroxydicarbonate. In particular, step a can be carried out in the presence of an effective amount of at least one radical initiator, in particular dilauroyl peroxide. Whatever its exact nature, the source of free radicals used according to the method of the invention is used under conditions allowing the production of free radicals, which is generally achieved by thermal activation, that is to say by raising the temperature of the reaction medium, generally at a temperature of the order of ambient (about 20 ° C) at 200 ° C, in particular from 40 ° C to 180 ° C, in particular from 80 ° C to 160 ° C. The production of free radicals can also be carried out at low temperature, generally at a temperature below ambient, in particular from 10 ° C. to -78 ° C., by using sources of free radicals sensitive to the process of autooxidation with oxygen. In general, the choice of the source of free radicals depends on the temperature at which it is desired to carry out the reaction. The quantity of the source of free radicals to be introduced into the medium depends on several parameters, in particular its efficiency, its mode of introduction, the purity of the reagents, the concentration of the reaction medium, the efficiency of the olefin as a radical trap. It is within the competence of those skilled in the art to adjust the amount of source of free radicals to be introduced into the medium as a function of these various parameters. Generally, the initiator is added in several stages to the reaction medium until total consumption of the compound of general formula (HA) or (HIA). The solvent used in step a- and fou b- is chosen from the solvents conventionally used in radical synthesis, such as 1,2-dichloroethane, dichloromethane, benzene, toluene, trifluoromethylbenzene (trifluorotoluene), chlorobenzene , hexane, cyclohexane, heptane, octane, ethyl acetate, tert-butyl alcohol, and mixtures thereof. The reaction is generally carried out at atmospheric pressure, at the boiling temperature of the chosen solvent. In the particular case of step b-, the radical cyclization is also generally carried out in an acid medium. In which case, the reaction can be carried out in the presence of a catalytic amount of acid, in particular camphorsulfonic acid. At the end of the reaction, the expected product of general formula (TVA) or (INB) can be isolated or directly transformed in the reaction medium into a compound of general formula (VA) or (VB).

The step of forming Poxime (VA) or (VB) can be carried out in a conventional manner. In particular, the compound of formula (IVA) or (TVB) can be brought into contact with an effective amount of nitromethane or hydroxylamine, and in particular of hydroxylamine salt such as, for example, hydroxylamine hydrochloride. Generally, the hydroxylamine is introduced in molar excess relative to the compound of general formula (TVA) or (INB), in particular it is present in an amount of approximately 1.3 equivalent. The oxime formation reaction of formula (VA) or (VB) can be carried out in various solvents such as, for example, methanol, ethanol, pyridine, toluene, benzene and their mixtures, and in particular in ethanol. In this oxime formation reaction, to the solution of compound of formula (INA) or (TVB) when a hydroxylamine salt is used, a weak base can be added, such as for example sodium acetate, triethylamine, ΝaHCO ₃ , Na ₂ CO ₃ and their mixtures. This weak base can be present in a content greater than or equal to 1 equivalent with respect to the compound of formula (VAT) or (TVB) and or less than 1 equivalent with respect to hydroxylamine. The mixture comprising at least one compound of formula (TVA) or (TVB) and hydroxylamine can be heated, and in particular brought to reflux, for example for a duration varying from 30 minutes to 3 hours. According to a particular variant, the preparation methods according to the invention can comprise a step of recovering the product of formula (VA) or (VB), in particular by recrystallization. However, the compound obtained may not be purified and be used as such in the next step. The preparation methods according to the invention comprise a step of transforming the compounds (VA) or (VB) by Beckmann rearrangement, according to a conventional method, as described for example by Donaruma and Heldt in Org. React. (NY) 1960, 11, 1. In particular, the Beckmann rearrangement can be carried out in the presence of an effective amount of a reagent such as, for example PCI5, concentrated HSO, formic acid, liquid SO ₂ , HMPA, SOCl ₂ , silica gel, P ₅ O ₅ - methanesulfonic acid, HCl-acetic acid-acetic anhydride or polyphosphoric acid (PPA). The PCI ₅ derivative proves to be particularly advantageous in particular by its effectiveness. It is generally brought into contact with the oxime of formula (VA) or (VB) in molar excess, in particular in a molar ratio greater than 2, in particular greater than or equal to 3, and very particularly ranging from 3 to 6. The Beckmann rearrangement can be carried out in many solvents such as for example pyridine, acetic acid, phenol toluene, benzene, ether, methylamine, cyclohexylamine, morpholine, dioxane, tetr-ydrofiirane (THF), chloroform, dichloromethane, aqueous hydrochloric acid solution , and in particular in dichloromethane. According to a particular embodiment, the oxime of formula (VA) and (VB) in solution is added dropwise to the solution of PCI ₅ , for example at 0 ° C. and the reaction is continued at room temperature. At the end of the reaction, the reaction mixture is neutralized, for example with an aqueous solution of saturated NaHCO ₃ , treated with an organic solvent, such as CH ₂ C1 ₂ , dried, filtered and then concentrated. The product thus obtained can be used without further purification in the next reduction step. The product resulting from the Beckmann rearrangement, isolated or not, can be reduced by an effective amount of at least one metallic reducing agent, such as for example magnesium, zinc or iron, and in particular zinc. This metallic reducing agent is generally used in molar excess, and in particular approximately 6 equivalents. This reduction can take place in different solvents such as, for example, acetic acid, methanol, ethanol or their mixtures. The temperature at which this reduction takes place can in particular vary from 0 ° C. to the boiling point of the solvent used. The product formed at the end of this reduction can be used without further purification in another reduction step, involving treatment with an effective amount of reducing agent, in particular BH ₃ and in particular BH ₃ .TΗF, POC- ₃ / NaBH- _t , PCIs / NaBH-i, LiAlH-j or diisobutylalurninium hydride (DIBAH). This second reduction can be carried out at reflux of the solvent, in particular at reflux of THF. This reduction mode involving the two types of consecutive reduction leads to compounds of formula (LA) or (IB) in which R ² and R ³ are hydrogen atoms. According to another variant, the reduction can be carried out in a single step with an effective amount of NaBH, the NaBH is generally present in molar excess relative to the Beckmann rearrangement product. In this particular embodiment, Beckmann rearrangement and reduction by NaBEU can be carried out sequentially in the same container. In the product of formula (LA) or (IB) obtained at the end of this reduction, the groups R ² and R ³ are chlorine atoms. According to another of its aspects, the present invention also relates to compounds of general formula (IA)

in which: R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and n are as defined above, and in particular R ⁷ can represent -XR ⁸ , XR ⁸ being as defined here -above. For example, the benzazepine compound can correspond to the formula (LA) in which n = 1, and in particular in which R ¹ is in the para position. According to a variant of the invention, the benzazepine compound can correspond to the formula (IA) in which R ² and R ³ each represent md endently a hydrogen atom, or an alkyl group. According to another variant of the invention, the benzazepine compound can correspond to the general formula (LA) in which R ² and R ³ each represent a chlorine atom. In particular, the group R ⁷ can represent: a group -XR ⁸ in which X can represent an oxygen atom and R ⁸ can be an acyl group such as for example C (= O) C (CH ₃ ) ₃ , or - a group ~ CH_) p CN in which p can represent an integer ranging from 1 to 10, and in particular 1, 2, 3 or 4. Among the compounds of formula (A) or (IB) there may be mentioned:

- 7-c oro-2,3,4,5-tetrahydro-1H-benzo [b] azepin-5-yl 2,2-dimethylpropionate,

- 2,2-dimethyl-propionate of 7-fluoro-2,3,4,5-t ^ rahydro-1H-benzoP-t] azépin-5-yl, - 2,2-dimethyl-propionate of 7- methoxy-2,3,4,5-tetrahydro-lH-benzo-azepin-5-yl,

- (7-fluoro-2,3,4,5-tasxahydro-1H-benzo [b] azepin-5-yl) -acetonitrile,

3,3,7-1richoloro-2,3,4,5-tetrahydro-1H-benzo [b] -azepin-5-yl 2,2-dimethylpropionate, and

- their derivatives.

According to yet another of its aspects, the subject of the present invention is the compounds of general formula (VB) in which: R ¹ , R ^2a , R ⁴ , R ⁵ , R ⁶ , XR ⁸ and n are as defined above. More particularly, this compound can be chosen from - 4 - [(E) -hydroxyimino] -7-chloro-1,2,3,4-tetrahydro-naphthalen-1-2,2-dimethyl propionate, - 2,2 dimethyl propionate of 4 - [(Ε) -hydroxyimino] -7-fluoro-1,2,3,4-tetrahydronaphtalen-1-yl, and - 2,2 dimethyl propionate of 4 - [(E) - hydroxyimino] -7-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl, and - their derivatives.

The present invention also relates to a process for the preparation of benzazepine of general formula (NIA):

in which :

R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and n are as defined above, and

R ¹⁰ represents a hydrogen atom, an alkyl or acyl group, and in particular a methyl group, comprising at least the transformation of a compound of general formula (IIA) into a compound of formula (LA) according to a process in accordance with l 'invention. The present invention also relates to a process for the preparation of benzazepine of general formula (VLB):

in which :

R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁸ , X and n are as defined above, and

R ¹⁰ represents a hydrogen atom, an alkyl or acyl group, and in particular a methyl group, comprising at least the transformation of a compound of general formula (TVB) into a compound of formula (LB), according to a process in accordance with the invention.

The following examples are given by way of illustration and without limitation of the present invention.

Examples

Preparation of the compounds of general formula (HA)

General method 1: To a solution containing 1 mmol of halogen derivative in acetone (2 mL) at 0 ° C protected from light and under argon are added, in portions, 1.1 equivalents of O-ethylxanthate potassium. The solution is stirred for 1 hour at room temperature, then the acetone is evaporated in vacuo and the residue is taken up in CH2Cl2. The organic phase is washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The residue obtained is purified by crystallization. Example 1: Dithiocarbonate 5-r2-f4-chloro-phenylV2-oxo-ethyll-O-ethyl Following the general method 1, a solution of 20 g is prepared. (85.6 mmol) of? -Chloro-bromoacetophenone in 172 mL of acetone at 0 ° C and 15.1 g. (94.2 mmol) of potassium O-ethylxanthate are added to this solution. After crystallization from water, the title product is obtained with a yield of 96% in the form of yellow crystals (mp = 64 - 65 ° C). RMN ^J H (CDC1 ₃ , 300 MHz): 7.96 (d, 2H, CJÏarom, J = 8.4 Hz), 7.47 (d, 2H, CH arom, J = 7.5 Hz), 4, 63 (q, 2H, O-CH2, J = 6.9 Hz), 4.62 (s, 2H, CO-CH_), 1.39 (t, 3H, C2I ₃ , J = 7.1 Hz); ¹³ C NMR (CDCI3, 62.9 MHz): 213.1 (CS), 194.8 (CO), 140.3 (C-CO), 134.2 (C-Cl), 129.9 (CH arom ), 129.1 (CH arom), 70.9 (CO-CH ₂ ), 43.4 (O-CH2), 13.8 (CH ₃ ).

EXAMPLE 2 Dithiocarbonate S- [2- (4-fluoro-phenylV2-oxo-yl1-O-ethyl) Following general method 1, a solution of 20 g (115.5 mmol) of 7-fluoro- is made. γ-chloroacetophenone in 232 mL of acetone at 0 ° C. and 20.4 g (127.4 mmol) of potassium O-ethylxanthate are added to this solution. After recrystallization from CH ₂ C1 ₂ / petroleum ether, the title product is obtained with a yield of 98% in the form of yellow crystals (mp = 58 - 61 ° C.) 1 H NMR (CDC1 ₃ , 400 MHz): 8.07 (dd, 2H, CH arom, J = 10 and 6 Hz), 7.18 (t, 2H, C-ffarom, J = 8 Hz), 4.64 (s, 2H, CO-Cflz), 4.63 (q, 2H, O-CH2, J = 6 Hz), 1.4 (t, 3H, C-rJ ₃ , J = 7.1 Hz); ¹³ C NMR (CDCI3, 100 * 5 MHz): 213.29 (CS), 190.93 (CO) , 167.43 (C-CO), 167.43; 164.88 (d, 1C, CF, ^ _C - _F = 256 Hz), 131.32 (CH arom), 131.23 (CH arom), 116 , 19 (CH arom), 115.97 (CH arom), 70.92 (CH ₂ -S), 43.48 (O-CH2), 13.73 (CH ₃ ); MS (ICP; m / z) : 276 (Mtf + NHs), 259 (Mît); IR (cm ¹ , CCU): 1688 (C = O), 1233 (C = S), 1052 (S- (S) CO) .

Example 3: Dithiocarbonate 5-r2-f4-methoxy-phenyl -2-oxo-emyl1-O-ethyl Prepared according to the protocol described in the translation Letters, 1997, 38, 1759-1762.

Preparation of products of general formula (THA)

General method 2: To a solution of 1 mmol of xanthate of formula (HA) in 1,2-dichloroethane (1 mL) are added 2 equivalents of the olefin of general formula (A). The solution is brought to reflux and degassed under an argon atmosphere. After 15 minutes at reflux, 0.05 mmol of dilauroyl peroxide (DLP) is added to the reaction mixture and 0.02 mmol every 1.5 hours until the total consumption of the starting product. When the reaction is finished, the solvent is evaporated in vacuo and the product purified by chromatography.

Example 4: 2.2-Dimethyl-ρropionate of l-ethoxythiocarbonylsul-ànyl-4-r4-chlorophenyr.-4-oxo-butyl Following the general method 2, a solution of 5 g. (18 mmol) of xanthate of Example 1 and 5.38 mL (3.1 g, 36.3 mmol) of vinyl pivalate in 18 L of 1,2-dichloroethane is brought to reflux and treated with DLP . The title product is obtained after chromatography on silica gel (eluent petroleum ether / ethyl acetate (95: 5)) with 97% yield (yellow oil). 1 H NMR (CDC1 ₃ , 400 MHz): 7.89 (d, 2H, Cff arom, J = 8 Hz), 7.44 (d, 2H, CH arom, J = 8 Hz), 6.71 (t, IH, C TS, J = 8 Hz), 4.62 (dq, 2H, OC-ff ₂ , J = 8 and 4 Hz), 3.1 (dt, 2H, CO-CH ^, J = 7.3 and 3.2 Hz), 2.41 (m, 2H, CH-C- ₂ ), 1.41 (t, 3H, CH ₂ -Cfl3, J = 8 Hz), 1.2 (s, 9H, ( 0 * 3) 3); ¹³ C NMR (CDCI3, 100 MHz): 210.02 (CS), 196.67 (CO), 176.77 (O-CO), 139.75 (C-CO), 134.82 (C-Cl) , 129.47 (2C, CH arom), 129.03 (2C, CH arom), 80.21 (CH-S), 70.33 (O-CH ₂ ), 38.9 (C- (CH ₃ ) ₃ ), 34.18 (CO-CH ₂ ), 28.46 (CH-CH2), 27.01 (3C, (CH ₃ ) ₃ ), 13.73 (CH ₂ -CH ₃ ); MS (TCP; m / z): 403 and 405 (MIT), 301 and 303 (MH ^ -OPiv); LR (cm ^-1 , CCL,): 1738 (OC = 0), 1692 (C = O), 1229 (OS), 1050 (SC).

Example 5: 2.2-Dimethyl-ρropionate of l-ethoxythiocarbonylsulfanyl-4- (4-fluorophenyl-oxo-butyl) Following general method 2, a solution of 5 g (19.3 mmol) of xanthate from the example 2 and 5.72 mL (4.9 g, 38.7 mmol) of vinyl pivalate in 19 mL of 1,2-dichloroethane is brought to reflux and treated with DLP. The title product is obtained after gel chromatography silica (eluent petroleum ether / ethyl acetate (95: 5)) with 90% yield (yellow oil). 1 H NMR (CDCI ₃ , 400 MHz): 7.97 (dd, 2H, GH ^" arom , J = 8.8 and 5.2 Hz), 7.14 (t, 2H, CH arom, J = 8.2 Hz), 6.71 (t, IH, CH S, J = 8 Hz), 4 , 63 (m, 2H, O-C0 ₂ ), 3.1 (dt, 2H, CO-C-H2, J = 7.5 and 2.9 Hz), 2.40 (m, 2H, CR-CH ₂ ), 1.42 (t, 3H, CH ₂ -Cfl ₃ , J = 8 Hz), 1.2 (s, 9H, (CH _) _); ¹³ C NMR (CDCI3, 100 MHz): 210.16 (CS), 196.4 (CO), 176.88 (O-CO), 167.2; 164.6 (d, 1C, CF, ^ _C -F = 255 Hz), 116.22 (C-CO ) 130.81 (CH arom), 130.72 (CH arom), 116.0 (CH arom), 115.79 (CH arom), 80.36 (CH- S), 70.40 (O-CH ₂ ) , 45.53 (C- (CH ₃ ) ₃ ), 34.19 (CO-CH ₂ ), 28.61 (CH-CH ₂ ), 27.07 (3C, (CH ₃ ) ₃ ), 13.79 (CH ₂ -CH ₃ ).

EXAMPLE 6 2.2-Dimethylpropionate of 1-ethoxymiocarbonylsulfanyl-4-f4-methoxyphenyl) -4-oxo-butyl According to general method 2, 0.5 g (1.85 mmol) of xanthate from Example 3 and 0.55 mL (2.7 mmol) of vinyl pivalate are dissolved in 2 mL of 1,2-dichloroethane. The product is purified by chromatography on silica gel (eluent petroleum ether / ethyl acetate (95: 5)) to give the title product with 86% yield (yellow oil). 1 H NMR (CDCI ₃ , 400 MHz): 7.92 (d, 2H, C-ffarom, J = 8.8 Hz), 6.93 (d, 2H, C-ffarom, J = 8.8 Hz), 6.71 (t, IH, CH-S, J = 8 Hz), 4.65-4.59 (m, 2H, O-Cflâ), 3.87 (s, 3H, OCH_), 3.08 ( dq, 2H, CO-CH ₂ , J = 7.2 and 4.4 Hz), 2.42-2.35 (m, 2H, CH-GH2), 1.41 (t, 3H, CH ₂ -C -ff ₃ , J = 6 Hz), 1.19 (s, 9H, (CH ₃ ) ₃ ); ¹³ C NMR (CDCI3, 100 MHz): 210.3 (CS), 196.6 (CO), 176.9 (O-CO), 163.7 (C-CO), 130.9 (C-OMe) , 130.4 (CH arom), 113.9 (CH arom), 80.4 (CH-S), 70.4 (O-CH2), 55.6 (OCH ₃ ), 43.5 (C- ( CH ₃ ) ₃ ), 33.9 (CO-CH ₂ ), 28.8 (CH-CH ₂ ), 27.1 (3C, (CH ₃ ) ₃ ), 13.8 (CH ₂ -CH ₃ ); MS (ICP; m / z): 416 (M - ^ + NHa), 399 (Mît), 297 (MH ⁺ -OPiv); IR (cm ¹ , CCI *): 1738 (O-OO), 1683 (C = O), 1229 (C = S), 1051 (S- (S) C- O).

Example 7: Dithiocarbonate 5-ri-cvanomethyl-4- ( ^' 4-fluoro-phenyl -4-oxo-butvn-O-ethyl Following the general method 2, a solution of 2 g. (7.74 mmol) of xanthate of Example 2 and 1.25 mL (1.03 g, 15.48 mmol) of allyl cyanide in 8 mL of 1,2-dichloroethane is brought to reflux and treated with DLP. The title product is obtained after chromatography on silica gel (eluent petroleum ether / ethyl acetate (9: 1)) with 81

% yield (yellow oil). 1H NMR (CDCI ₃ , 400 MHz): 7.98 (dd, 2H, Cfl ^" arom, J =

8.4 and 5.2 Hz), 7.14 (t, 2H, C-ffarom, J = 8.4 Hz), 4.63 (ddd, 2H, 0-CH ₂ , J = 10.2 and 7 , 1 and 1.4 Hz), 4.01 (dddd, IH, CH-S, J = 15.2, 5.3, 5.3 and 5.3 Hz), 3.19 (t, 2H, CO -CH ₂ , J = 7.2

Hz), 2.96 (t, 2H, CH ₂ -CN), 2.39 (ddt, IH, CO-CH ₂ -CfT ₂ , J = 10.9, 7.2 and 4.3 Hz), 2 15

(dddd, IH, CO-CΑ ₂ -CH ₂ , J = 18, 7.2, 6.8 and 6.8 Hz), 1.42 (t, 3H, CH ₂ -C-ff ₃ , J = 7 Hz);

¹³ C NMR (CDCI3, 100 MHz): 212.03 (CS), 196.5 (CO), 165.97 (d, 1C, CF, ^ CF = 255.2

Hz), 132.93 (C-CO), 130.7 (d, 2C, CH arom, ² J _C - _F = 13 Hz), 117.08 (CNN), 115.9 (d, 2C, CH arom , ³ J _C - _F = 22 Hz), 70.74 (O-CH ₂ ), 46.24 (CH-S), 35.42 (CO-CH ₂ ), 26.72 (CH ₂ - CN), 24.5 (CO-CH ₂ -CH ₂ ), 13.81 (CH2-CH3); MS (ICP; m / z): 342 (-SHT + NHa), 325 (Mît), 205 ; IR (cm ^"1 , CCU): 2250 (C≡N), 1741 (C = O), 1236 (OS), 1051 (S- (S) CO).

Preparation of tetralones of formula (VAT) or (TVB)

General method 3: A solution of 1 mmol of compound of formula (HIA) and 0.1 mmol of camphorsulphonic acid (ACS) in 1,2-dichloroethane (10 mL) is brought to reflux and degassed under an atmosphere of argon. After 15 minutes at reflux, 0.2 mmol of DLP is added to the reaction mixture and 0.2 mmol every hour until the total consumption of the starting product is consumed. When the reaction is finished, the solvent is evaporated in vacuo and the product purified by chromatography.

Example 8: 2.2-Dimethyl-propionate of 7-chloro-4-oxo-1.2.3.4-tet - hvdro-naphthalén-l-yle Following general method 3, a solution of 3.5 g (8.67 mmol ) of compound of Example 4 and 0.2 g (0.86 mmol) of ACS in 87 ml of 1,2-dichloroethane is brought to reflux and treated with DLP. The title product is purified on a column of silica gel, eluent petroleum ether / ethyl acetate (9: 1) and recrystallized from petroleum ether to obtain a slightly yellow solid (mp = 76 - 80 ° C) with 84% yield. NMR

1H (CDCI ₃ , 400 MHz): 8.0 (d, IH, CH arom, J = 8 Hz), 7.42 (d, IH, Cffarom, J = 8 Hz), 7.41 (s, IH, Cffarom), 6.05 (dd, IH, GH-OPiv, J = 8 and 4 Hz), 2.9 (ddd, IH, CO-C-H2, J =

18, 10 and 4 Hz), 2.69 (ddd, IH, CO-GH2, J = 20, 8 and 4 Hz), 2.41 (m, IH, CO-CH ₂ -ClT ₂ ),

2.26 (m, 1H, CO-CH2-C-H2), 1.25 (s, 9H, CH_); ¹³ C NMR (CDCI ₃ , 100 MHz): 195.32

(CO), 177.34 (O-CO), 142.5 (C-CO), 139.94 (C-Cl), 129.92 (CC-CO), 128.91 (CH arom), 128, 64 (CH arom), 127.45 (CH arom), 67.99 (CH-OPiv), 38.66 (C- (CH ₃ ) ₃ ), 34.24 (CO-CH ₂ ), 28.14 ( CO-CH2-CH2), 27.14 (3C, CH ₃ ); MS (ICP; m / z): 297 and 299

(MH ^ + NHa), 281 and 283 (Mît), 180 and 182 (ME ^ -OPiv); IR (cm ¹ , CCI ₄ ): 1733 (OC = 0),

1696 (C = O), 1143 (O-OO); Microanalysis calculated for Cι ₅ Hι ₇ O ₃ Cl: C, 64.17; H

6,103. Found: C, 64.04; H, 6.25. Example 9: 2-2-Dimethyl-proρionate of 7-fluoro-4-oxo-1.2.3.4-tetrahvdro-naphthalen-l-yle Following general method 3, a solution of 3 g (7.76 mmol) of compound of Example 5 and 0.18 g (0.77 mmol) of ACS in 78 ml of 1,2-dichloroethane is brought to reflux and treated with DLP. The title product (yellow oil) is obtained with 54% yield after purification by chromatography on silica gel, eluent petroleum ether / ethyl acetate (9: 1). ^Α H NMR (CDC1 ₃ , 400 MHz): 7.97 (dd, IH, CH arom, J = 8.8 and 5.2 Hz), 7.12 (m, 2H, CH arom), 6.06 ( dd, IH, C-ff-OPiv, J = 8 and 4 Hz), 2.89 (ddd, IH, CO-CH ₂ , J = 20, 8 and 4 Hz), 2.68 (ddd, IH, CO -CH ₂ , J = 16.8, 8 and 4 Hz), 2.42 (m, 1H, CO-CH2-C-H2), 2.24 (m, 1H, CO-CH2-CH2), 1, 25 (s, 9H, (CH ₃ ) ₃ ); ¹³ C NMR (CDCI ₃ , 100.5 MHz): 195.4 (CO), 176.3 (O-CO), 144.5 (CF), 130.59 (d, 1C, CH arom, ³ Jc- F = 10.5 Hz), 116.41 (d, 1C, CH arom, ² J _C - _F = 23 Hz), 115.94 (C-CO), 115.50 (C- CCO), 114.4 (d, 1C, CH arom, J _C - _F = 23 Hz), 68.62 (CH-OPiv), 39.09 (C- (CH ₃ ) ₃ ), 34.75 (CO-CH2), 28, 7 (CO-CH ₂ -CH ₂ ), 27.17 (3C, (CH ₃ ) ₃ ).

Example 10: 2.2-Dimethyl-propionate of 7-methoxy-4-oxo-1.2.3.4-tetrahydro-naphthalen- 1-yle According to the general method 3, 3 g (7.5 mmol) of compound of Example 6 are dissolved in 75 mL of 1,2-dichloroethane and treated with DLP. The title product is purified on a column of silica gel, eluting petroleum ether / ethyl acetate (9: 1) and recrystallized from ethanol to obtain a yellow solid (mp = 80 ° C) with 30% yield . ^Α H NMR (CDCI ₃ , 400 MHz): 8.06 (d, IH, C # arom, J = 8 Hz), 6.96 (dd, IH, CET arom, J = 8 and 4 Hz), 6, 89 (d, IH, CH arom, J = 4 Hz), 6.08 (dd, IH, CAT-OPiv, J = 8 and 4 Hz), 3.89 (s, 3H, OC-H ₃ ), 2 , 87 (ddd, IH, CO-CH ₂ , J = 18, 9 and 6 Hz), 2.66 (ddd, IH, CO-CH2, J = 16, 8 and 4 Hz), 2.45-2, 37 (m, 1H, CO-CR ₂ -CH ₂ ), 2.29-2.21 (m, 1H, CO-CR ₂ -CH ₂ ), 1.26 (s, 9H, CH ₃ ); ¹³ C NMR (CDCI ₃ , 100.5 MHz): 195.75 (CO), 177.91 (O-CO), 163.99 (C-CO), 143.7 (C-OMe), 129.85 (CH arom), 125.47 (CC-CO), 114.94 (CH arom), 111.92 (CH arom), 69.13 (CH-OPiv), 55.59 (OCH ₃ ), 39.07 (C- (CH ₃ ) ₃ ), 34.61 (CO-CH ₂ ), 28.77 (CO-CH ₂ -CH ₂ ), 27.18 (3C, CH ₃ ); MS (ICP; mz): 294 (MH NH3), 277 (Mît), 176 (MH ⁺ - OPiv); TR (cm ^'1 , CC): 1731 (O- O), 1687 (OO), 1146 (0- O); Microanalysis calculated for Cι ₆ H ₂ oO: C, 69.54; H, 7.3. Found: C, 69.07; H, 7.27. Example 11: (7-Fluoro-4-oxo-l-2 ₁ 3.4-tetrahvdro-naphthalen-l-yl1-acetonitrile Following general method 3, a solution of 2 g (6.14 mmol) of compound of Example 7 and 0.143 g (0.61 mmol) of ACS in 61 mL of 1,2-dichloroethane is brought to reflux and treated with DLP. The title product is purified on a column of silica gel, eluent ether of petroleum / ethyl acetate (8: 2) and recrystallized from petroleum ether to give a yellow solid (mp = 126-128 ° C) with 36% yield NMR ^J H (CDC1 _3, 400 MHz).: 8.12 (dd, IH, Cffarom, J = 9 and 5.8 Hz), 7.1 (dt, IH, C-ffarom, J = 8.2 and 2.4 Hz), 7.05 (d, IH, CH arom, J = 9.6 Hz), 3.38 (tt, IH, CH, J = 11.6 and 6.1 Hz), 2.75-2.83 (m, 3H, C -CH ₂ and C-ff ₂ -CN), 2.68 (ddd, IH, C-ff ₂ -CN, J = 18, 7.4 and 5 Hz), 2.45 (dddd, IH, CO-CH2-C .H2, J = 19, 9.4 and 4.6 Hz), 2.2-2.28 (m, 1H, CO-CH ₂ -C-ff ₂ ); ¹³ C NMR (CDCI ₃ , 100.5 MHz): 194.9 (CO), 166.06 (d, 1C, CF, ^l J -v = 256 Hz), 146.05 (C-CO), 131.3 (d, 1C, CH arom, ³ J _C. _F ≈ 10.9 Hz), 121.98 (C≡ N), 117.64 (C-CCO), 115.86 (d, 1C, CH arom, ² J _C - _F = 23 Hz), 114.24 (d, 1C, CH arom, ² J _C - _F = 22 Hz), 35.14 (CH), 34.95 (COCH ₂ ), 27.58 (CH2-CN), 22, 95 (CO-CH ₂ -CH ₂ ); MS (ICP; m / z): 221 (MH '+ NHs), 204 (Mît); R (cm ^-1 , CCI): 2254 (C≡ N), 1693 (OO), 1250 (CF); Microanalysis calculated for Cι ₂ Hι ₀ NOF: C, 70.93; H, 4.96; N, 6.44. Found: C, 70.53; H, 5.03; N, 6.56.

Preparation of oximes of formula (VA) or (VB)

General method 4: To a solution containing 1 mmol of tetralone of formula (LVA) or (IVB) in ethanol (0.75 mL) is added another solution made of 1.3 equivalents of NH ₂ OHΗCl and 1.2 equivalents of sodium acetate in water (0.3 L). The resulting solution is brought to reflux for 2 hours, then the ethanol is evaporated in vacuo and the reaction mixture is extracted with ethyl acetate. The organic phase is dried over sodium sulfate, filtered and concentrated in vacuo.

Example 12: 2.2-Dimethyl-proρionate of 4-r (E) -hvdroxyiminol-7-chloro-1.2.3,4- tétrahvdro-naphthalen- 1 -vie

Following general method 4, to a solution of 1.99 g (7.11 mmol) of tetralone of Example 8 in 5.3 ml of ethanol is added a solution of 0.596 g (9.24 mmol) of NH ₂ OHΗCl and 1.16 g (8.53 mmol) of sodium acetate in 2.1 mL of water. The mixture is brought to reflux and treated as described. Then, the title product is recrystallized from petroleum ether and a yellow solid (mp = 110-112 ° C) is isolated with a yield of 96%. 1 H NMR (CDC1 ₃ , 400 MHz): 9.19 (si, IH, OH), 7.86 (d, IH, CH arom, J = 8 Hz), 7.35 (d, IH, Ci-T arom , J = 4 Hz), 7.29 (dd, IH, CH arom, J = 8 and 4 Hz), 5.89 (t, IH, CH-OPiv, J = 4 Hz), 2.93 (t, 2H, C (NOH) -C -T ₂ , J = 6 Hz), 2.07 (m, 2H, CH-CH ₂ ), 1.22 (s, 9H, (CH ₃ ) ₃ ); ¹³ C NMR (CDC1 ₃ , 100 MHz): 178.03 (O-CO), 153.35 (C- NOH), 138.27 (CC (NOH)), 135.65 (C-Cl), 129, 04 (CH arom), 128.87 (CCC (NOH)), 128.0 (CH arom), 125.69 (CH arom), 68.99 (CH-OPiv), 39.09 (C- (CH ₃ ) ₃ ), 27.19 (3C, (CH ₃ ) ₃ ), 26.33 (C (NOH) -CH ₂ ), 19.33 (CH-CH ₂ ).

Example 13: 4-rffiVhv 2.2-Dimethyl-propionate (lroxyiînino1-7-fluoro-l.2.3.4- tétrahvdro-naphthalen- 1 -vie

Following general method 4, to a solution of 1.14 g (4.31 mmol) of tetralone of Example 9 in 3.2 ml of ethanol is added a solution of 0.362 g (5.6 mmol) of NH2OHΗCI and 0.425 g (5.17 mmol) of sodium acetate in 1.3 mL of water. The reaction is brought to reflux and treated as described. Then, the product is recrystallized from petroleum ether and a yellow solid (mp = 125 - 128 ° C) is isolated with a yield of 92%. 1 H NMR (CDCI ₃ , 400 MHz): 9.10 (si, IH, OH), 7.92 (dd, IH, Tarom, J = 8.8 and 6 Hz), 7.05 (dt, IH, CH arom, J = 8.5 and 2.5 Hz), 7.02 (dd, H, CH arom, J = 8.2 and 3

Hz), 5.89 (dd, IH, CH-OPiv, J = 7 and 3.8 Hz), 2.94 (m, 2H, C (NOH) -CH ₂ ), 2.07 (m, 2H,

CÎL-CH ₂ ), 1.23 (s, 9H, CH ₃ ); ¹³ C NMR (CDC1 ₃ , 100.5 MHz): 178.04 (O-CO), 164.7;

162.21 (d, 1C, CF, ^ _C - _F = 250 Hz), 153.32 (C (NOH)), 139.2 (d, 1C, CH arom, ³ Jc- _F = 8

Hz), 126.55 (CC (NOH)), 116.19 (d, 1C, CH arom, ² J _C - _F = 22 Hz), 114.35 (d, 1C, CH arom, ² J _C - _F = 23 Hz), 69.13 (CH-OPiv), 39.08 (C- (CH ₃ ) ₃ ), 27.18 (3C, (CH ₃ ) ₃ ), 26.47

(C (NOH) -CH ₂ ), 19.48 (CH-CH ₂ ); MS (ICP; m / z): 297 (MKf '+ NHa), 280 (Mît), 179

(MET'-OPiv); IR (cm ^-1 , CCL: 3593 (N-OH), 3300 (OH, Hydrogen bond), 1730 (O-

C = 0), 1279 (O-CO).

Example 14: 2.2-Dimethyl-ρropionate of 4-r (Ε) -hvdroxyimino1-7-methoxy-l .2.3,4- tetrahydro-naphthalen- 1 -vie According to general method 4, 0.065 g (1.011 mmol) of hydrochloride hydroxylamine and 0.127 g (0.933 mmol) of sodium acetate are dissolved in 0.2 mL of water. This solution is added to a solution containing 0.215 g (0.778 mmol) of tetralone from Example 10 in 0.6 ml of ethanol and brought to reflux. After treatment, the title product is recrystallized from petroleum ether and a yellow solid is obtained (mp = 114-115 ° C) with a yield of 92%. 1 H NMR (CDC1 ₃ , 400 MHz): 9.34 (si, IH, OH), 7.86 (d, IH, CH arom, J = 8 Hz), 6.9 (d, IH, CH arom, J = 2 Hz), 6.87 (dd, IH, CH arom, J≈ 7.8 and 2.2 Hz), 5.91 (dd, IH, Cfl-OPiv, J≈ 6 and 4 Hz), 3, 82 (s, 3H, OCH3), 2.93 (t, 2H, C (NOH) -C-H2, J≈ 6.8 Hz), 2.04-2.11 (m, 2H, CH-C- H2), 1.22 (s, 9H, (CH ₃ ) ₃ ); ¹³ C NMR (CDCI ₃ , 100.5 MHz): 178.13 (O-CO), 160.66 (C-NOH), 153.75 (CC (NOH)), 138.38 (C- OMe), 125.8 (CH arom), 122.99 (CCC (NOH)), 115.38 (CH arom), 112.15 (CH arom), 69.65 (CH-OPiv), 55.44 (OCH ₃ ) , 39.09 (C- (CH ₃ ) ₃ ), 27.22 (3C, (CH ₃ ) ₃ ), 26.63 (C (NOH) - CH ₂ ), 19.43 (CH-CH2); MS (ICP; m / z): 292 (Mît), 191 (MH'-OPiv); IR (cm ^-1 , CC): 3596 (N-0-ff), 1727 (O-OO), 1604 (OtV-OH), 1272 (0-OO).

Example 15: {7-Fluoro-4-r (EVhvdroxyimino1 - 1.2.3.4-tetrahydro-naphthalen- 1 -vil - acetonitrile Following general method 4, to a solution of 0.4 g (1.96 mmol) of tetralone of example 11 in 0.9 ml of ethanol is added a solution of 0.165 g (2.55 mmol) of NH ₂ OHΗCI and 0.321 g (2.36 mmol) of sodium acetate in 0.4 ml of The reaction is brought to reflux and treated as described The title product is then recrystallized from ethyl acetate / petroleum ether to give a yellow solid (mp = 167-168 ° C) with a yield 78% ^X H NMR (CDC1 _3, 400 MHz):. 9.94 (bs, IH, OH), 7.97 (dd, IH, arom CET, J≈ 8.8 and 6Hz), 6.93 -7.0 (m, 2H, CET arom), 3.16-3.22 (m, m, CH), 2.96 (dt, IH, C (NOH) -CH ₂ , J≈ 18.8 and 5.2 Hz), 2.73 (dtd, IH, C (NOî £) -CH ₂ , J≈ 27, 8.3 and 2 Hz), 2.58-2.66 (m, IH, CH ₂ - CN), 2.05-2.12 (m, 2H, CH-C-δT ₂ ); ¹³ C NMR (CDCI ₃ , 100 MHz): 162.3 (d, 1C, CF, V _C - _F = 250 Hz), 150.71 (ONOH), 140.02 (C- ONOH), 126, 8 (C≡ N), 126.24 (d, 1C, CH arom, ³ J _C - _F ≈ 7.7 Hz), 117.77 (C-CH), 114.36 (d, 1C, CH arom, ² J _C - _F = 15 Hz), 113.56 (d, 1C, CH arom, ² J _C - _F ≈ 23 Hz), 34.73 (CH), 24.8 (C (NOH) -CH ₂ ) , 21.93 (CH ₂ -CN), 19.15 (CH-CH ₂ ); MS (ICP; m / z): 236 (MH ⁺ + NH ₃ ), 219 (Mît); LR (cm ¹ , CCI): 3591 (N-OH), 1741 (OiV-OH), 1239 (O- O).

Preparation of Benzazepines of formula (IA) or (IB)

General method 5: A solution of 1 mmol of the oxime of formula (VA) or (VB) in 10 ml of dichloromethane is added dropwise to another solution containing 4 mmol of PC1 ₅ in dichloromethane (10 ml) at 0 ° C. The solution is then stirred at room temperature for 2 hours and is then neutralized with aqueous NaHCO ₃ solution, extracted with CH ₂ Cl ₂ , dried over sodium sulfate, filtered and concentrated. The oil thus obtained is dissolved in 10 ml of acetic acid and brought to reflux, after which 6 mmol of powdered Zn are added slowly to this solution and the reflux is maintained for 30 minutes. The resulting mixture is then diluted with ethyl acetate, filtered through celite, washed with saturated N-1HCO _{3 solution} and concentrated in vacuo. The product obtained in this way is then dissolved in 1.5 ml of THF and added dropwise to a solution of 2 mmol of BH ₃ ΗF complex in 1.5 ml of THF at 0 ° C. The solution is brought to reflux for 30 minutes and allowed to cool, then it is treated with a few drops of a saturated solution of citric acid, the THF is evaporated, the aqueous phase is basified with an aqueous solution of Na2θO ₃ and extracted with CH2Cl2. The residue obtained is purified by chromatography.

Example 16: 2.2-Dimethyl-ρroρionate de 7-cMoro-2.3.4,5-tétrahvdro-1H-benzorZ, 1azépin- 5-yl ester Following the general method 5, a solution of 1.1 g (3.71 mmol ) of oxime of Example 12 in 37 ml of CΗ ₂ C1 ₂ is treated with a solution of 3.1 g (14.8 mmol) of PCI ₅ in 37 ml of CH ₂ C1 ₂ . The residue thus isolated is dissolved in 35 ml of acetic acid and then 1.4 g (21.45 mmol) of Zn are added. A solution of 1.1 (3.71 mmol) of the product thus obtained in 5.5 ml of THF is reduced with a 1 M solution of BH ₃ -THF in 5.5 ml of THF according to the general method. The title product is purified on a column of silica gel, eluting petroleum ether / ethyl acetate (9: 1) to obtain a white solid (m.p. = 65 - 66 ° C) with a yield of 40% on the 3 stages. 1 H NMR (CDCI ₃ , 400 MHz): 7.27 (d, IH, C-ETarom, J≈ 2.4 Hz), 7.02 (dd, IH, C-ETarom, J≈ 8.4 and 2, 4 Hz), 6.64 (d, IH, C-ETarom, J≈ 8.8 Hz), 5.84 (d, IH, GET-OPiv, J≈ 8 Hz), 3.83 (si, IH, NET), 3.25 (dt, IH, NH-Cfl2, J≈ 13.2 and 4.2 Hz), 2.93 (ddd, IH, NH-GET ₂ , J≈ 13.2, 9.6 and 3.2 Hz), 1.8-2.0 (m, 4H, NH-C-Θ2 and NH-CH ₂ -GEr ₂ ), 1.27 (s, 9H, (C-ET ₃ ) ₃ ); ¹³ C NMR (CDCI3, 100 MHz): 177.35 (O-CO), 147.5 (C-Cl), 131.54 (C-NH), 128.14 (CH arom), 127.74 (CH arom), 125.23 (C-CNH), 120.75 (CH arom), 73.72 (CH-OPiv), 47.53 (NH-CH ₂ ), 41.7 (C- (CH ₃ ) ₃ ), 31.3 (CH-Cfla), 27.31 (3C, (CH ₃ ) ₃ ), 27.0 (NH-CH ₂ -CH ₂ ); MS (ICP; m / z): 282 and 284 (Mît), 181 and 184 (MH ⁺ -OPiv); IR (cm ^"1 , CCI,): 3386 (NH), 1729 (O-OO), 1151 (O- O); Microanalysis calculated for C ₁₅ H ₂₀ NO ₂ C1: C, 63.94; H, 7, 15. Found: C, 63.75; H, 7.15 Example 17: 2.2-Dimethyl-propionate of 7-fluoro-2.3.4.5-tetrahvdro-1H-benzor & 1azepin-5-yle Following the general method 5, a solution of 0.956 g (3.42 mmol) of oxime of Example 13 in 34 ml of CΗ ₂ C1 ₂ is treated with a solution of 2.85 g (13.6 mmol) of PC1 ₅ in 34 ml of CH ₂ C1 _2. The residue thus obtained is dissolved in 34 ml of acetic acid and 1.34 g (20.5 mmol) of Zn are added, a solution of 0.875 g (3.13 mmol) of product thus obtained in 4 , 7 mL of THF is reduced with a 1 M solution of BH ₃ HF in 4.7 mL of THF according to the general method The title product is purified on a column of silica gel, eluting petroleum ether / ethyl acetate (9: 1) to obtain a white solid (mp = 58-60 ° C.) with a yield of 61% over the 3 steps. 1 H NMR (CDCI3, 400 MHz): 7.05 (dd, 1 H, Ctf arom, J≈ 9.4 and 3 Hz), 6.78 (td, IH, CE arom, J≈ 8.3 and 3.1 Hz), 6.68 (dd, IH, CET arom, J≈ 8 , 4 and 4.8 Hz), 5.84 (d, IH, Cff-OPiv, J≈ 10 Hz), 3.58 (sL IH, NH), 3.26 (dt, IH, NH-CH ^" ₂ , J≈ 13.2 and 4.2 Hz), 2.79 (td, IH, NH-C-ET ₂ , J ≈ 11.7 and 2.8 Hz), 1.7-2.0 (m, 4H, CH-CET ₂ and NH-CH ₂ -OET ₂ ), 1.26 (s, 9H, (CT-T ₃ ) ₃ ); ¹³ C NMR (CDCI3, 100.5 MHz): 177.2 (O-CO), 157.7 (d, IC, CF,. _F = 236 Hz), 144.4

^" (C-NH), 133.19 (C-CH), 120.94 (d, IC, CH arom, ² J _C. _F = 7 Hz) 114.06 (d, IC, CH arom, ² Jc- _F = 7 Hz), 113.71 (d, IC, CH arom, ³ J _C - _F = 24 Hz), 73.57 (CH-OPiv), 47.57 (NH-CH ₂ ), 39.04 ( C- (CH ₃ ) ₃ ), 32.03 (NH-CH ₂ -CH ₂ ), 27.52 (CH-CH ₂ ), 27.31 (3C, (CH ₃ ) ₃ ); MS (ICP; m / z): 266 (Mît), 165 (M ^ -OPiv); LR (cm ^"1 , CC14): 3385 (NH), 1729 (O-OO), 1152 (O- O); Microanalysis calculated for Cι ₅ H ₂₀ NO ₂ F: C, 67.9; H, 7.6 Found: C, 67.93; H, 7.62.

Example 18: 2.2-Dimethylpropionate of 7-methoxy-2.3A5-tetrahvdro-1H-benzorfrlazepin-5-yle According to general method 5, a solution of 0.1 g (0.343 mmol) of oxime from Example 14 in 3.4 mL of CΗ2CI2 is first treated with 0.286 g (1.37 mmol) of PCI ₅ in dichloromethane (3.4 mL). Second, the crude reaction thus obtained is dissolved in acetic acid (3.4 mL) and 0.135 g (2.05 mmol) of powdered Zn is added. Finally, ramide is reduced with 0.68 mL (0.68 mol) of solution 1 M of BH ₃ "TΗF in 1 mL of THF. The title product is purified on a column of silica gel, eluting petroleum ether / ethyl acetate (9: 1) to obtain a yellow oil with a yield of 21% over the 3 stages. ^Α H NMR (CDC1 ₃ , 400 MHz): 6.93 (d, IH, C-ETarom, J = 2.4 Hz), 6.66-6.7 (m, 2H, CH arom), 5.87 (d, IH, GET-OPiv, J ^≈ 9.2 Hz), 3.76 (s, 3H, OGH ₃ ), 3.24 (dt, IH, NH-C-ET ₂ , J≈ 12.8 and 4.2 Hz), 2.78 (td, IH, NH-GET ₂ , J = 11.7 and 2.8 Hz), 1.75-2.0 (m, 4H, CH-C-ET ₂ and NH-CH2-CET2), 1.28 (s, 9H, (C-ET ₃ ) ₃ ); ¹³ C NMR (CDC1 ₃ , 100 MHz): 189.11 (O-CO), 141.93 (C-OMe), 134.04 (C-NH), 130.24 (C-CH), 120.99 (CH arom), 112.97 (CH arom), 112.49 (CH arom), 74.06 (CH-OPiv), 55.57 (OCH ₃ ), 48.23 (NH-CH2), 39.1 (C- (CH ₃ ) ₃ ), 32.33 (NH-CH2-CH2), 27.73 (CH-CH ₂ ), 27.38 (3C, (CH ₃ ) ₃ ); MS (ICP; m / z): 278 (Mît), Vil (Mlf-OPiv); IR (cm ^"1 , CC): 3450 (NH), 1727 (O-OO), 1156 (0-00).

Example 19: (7-Fluoro-2.3.4.5-téfaahvΦo-1H-berιzortlazépin-5-ylVacétomtrile Following general method 5, a solution of 0.25 g (1.14 mmol) of oxime from Example 15 in 12 mL of CΗ ₂ C1 ₂ is treated with a solution of 0.954 g (4.58 mmol) of PCI ₅ in 12 mL of CH ₂ C1 _2. The residue thus obtained is dissolved in 12 mL of acetic acid and 0.45 g (6.87 mmol) of Zn are added and a solution of 0.25 g (1.14 mmol) of product thus obtained in 2 ml of THF is reduced with 2.3 ml (2.3 mmol) of solution 1 M of BH ₃ THF in 2 mL of THF according to the general method The title product is purified on a column of silica gel, eluting petroleum ether / ethyl acetate (9: 1) to obtain a white solid (mp = 74 - 75 ° C) with a yield of 39% over the 3 stages. 1 H NMR (CDCI ₃ , 400 MHz): 6.84 (dd, IH, C-ETarom, J = 9.2 and 2.4 Hz) , 6.78 (td, IH, CH arom, J≈ 8.2 and 3 Hz), 6.67 (dd, IH, CET arom, J≈ 8.4 and 4.8), 3.59 (if, IH, Nfl), 3.19-3.29 (m, 2H, CH and NH-CEfc), 3.0 (dd, IH, C-ET ₂ -CN, J≈ 16.6 and 8.6 Hz), 2.81 (dd, IH, CH ₂ - CN. J = 16.6 and 7.4 Hz), 2.72 (ddd, IH, NH-C-ET ₂ , J≈ 12.6, 10.8 and 2 Hz), 2.05-2.1 (m , IH, NH-CH ₂ -C / Ï2), 1.84-1.95 (m, IH, NH-CH2-C-ET2), 1.71-1.79 (m, 2H, CH-CH ₂ ); ¹³ C NMR (CDCI ₃ , 100 MHz): 157.78 (d, IC, CF, = 241 Hz), 145.67 (C-NH), 134.36 (d, IC, CH arom, ³ Jc- _F ≈ 6 Hz), 121.75 (O), 119.17 (C-CH), 116.66 (d, IC, CH arom, ² Jc- _F = 22.1 Hz), 114.25 (d, IC , CH arom, 2JC-F = 19.1 Hz), 48.97 (NH-CH2), 42.49 (CH), 29.94 (CH ₂ -CN), 26.11 (NH-CH ₂ -CH ₂ ), 19.12 (CH-CH ₂ ); MS (ICP; m / z): 206 (Mît); LR (cm ^" CCl _t ): 3384 (NH), 2246 (ON), 1253 (O-OO); Microanalysis calculated for Cι ₂ H ₁₃ N ₂ F: C, 70.57; H, 6.42. Found: C, 70.42; H, 6.55. Example 20: 2.2-Dimethyl-propionate of 3.3.7-trichloro-2.3.4.5-tetrahvdro-1H-benzorfrlazepin-5-yl To a solution of 0.28 g (1.35 mmol) of PC1 ₅ in 1.5 mL of CH ₂ C1 ₂ at 0 ° C. is added, drop by drop, a solution of 0.1 g (0.338 mmol) of oxime of Example 12 in the same solvent. The reaction is then stirred at room temperature until the starting material disappears. Then, the reaction is cooled to 0 ° C and a suspension of 0.128 g (3.38 mmol) of NaBELt in 0.3 ml of ethanol is added slowly to the reaction medium. Stirring is continued at 0 ° C until the end of the reaction. Finally, the reaction mixture is extracted with dichloromethane. The organic phase is dried over sodium sulfate, filtered and concentrated in vacuo. The residue thus obtained is purified by chromatography on silica gel, eluent petroleum ether / ethyl acetate (95: 5) to provide a white solid (mp = 103 -104 ° C) with a yield of 48% out of 2 steps. ^X H NMR (CDC1 _3, 400 MHz): 7.21 (d, IH, C 7arom, J≈ 2Hz?), 7.10 (d, IH, CH arom, J≈ 8.8 and 2.4 Hz ), 6.72 (d, IH, CH arom, J≈ 8.4 Hz), 6.03 (t, IH, CTT- OPiv, J≈ 5.6 Hz), 4.22 (sL IH, N- ET), 3.75 (dd, IH, CH-C-ff ₂ , J = 14.8 and 6.8 Hz), 3.57 (d, IH, CH-C-H2, J = 14 Hz), 3.86 (d, 2H, NH-C-ET ₂ , J≈ 4 Hz), 1.29 (s, 9H, (CH ₃ ) ₃ ); ¹³ C NMR (CDCI ₃ , 100 MHz): 177.0 (O-CO), 145.21 (C-Cl), 142.32 (C-NH), 128.52 (CH arom), 128.23 ( CH arom), 126.62 (C-CH), 120.98 (CH arom), 88.36 (CC1 ₂ ), 69.19 (CH-OPiv), 61.65 (CH-CH ₂ ), 50, 08 (NH-CH ₂ ), 38.97 (C- (CH ₃ ) ₃ ), 27.27 (3C, (CH ₃ ) ₃ ); MS (ICP; m / z) ^' : 350 and 352 (Mît), 248 and 250 (MH ^ -OPiv); IR (cm ^"1 , CCI4): 3446 (NH), 1735 (O-OO), 1139 (O-OO); Microanalysis calculated for Cι ₅ Hι ₈ NO ₂ Cl ₃ : C, 51.38; H, 5, 17. Found: C, 51.31; H, 5.16.

General method 6: A solution containing X mmol of amine and 4 X mmol of sorted ylarnine, dissolved in dichloromethane (5 ml / mmol), is stirred at 0 ° C. in an ice-water bath. To this solution are added dropwise 3 X mmol of acid chloride dissolved in 5 mL / mmol of dichloromethane. The reaction mixture is left at 0 ° C for 15 minutes, then allowed to return to room temperature. When the starting material is completely consumed (about 1 hour), the reaction is basified by adding a few drops of saturated solution of saturated Na ₂ Cθ3 and the product is extracted with ethyl acetate. The solution is dried, filtered, concentrated in vacuo and purified by chromatography on silica gel.

Example 21: 2.2-Dime yl-propionic acid 7-chloro-l- (2-methyl-4-nitro-benzoylV2.3.4.5- tetrahvdro-1H-benzor> lazepin-5-yl ester Following general method 6, a solution of 0.212 g (1.06 mmol) of 2-methyl-4-nitrobenzoyl chloride in 2 ml of dichloromethane in a solution of 0.1 g (0.35 mmol) of the compound of Example 16 is added and 2 mL (0.143 g, 1.41 mmol) of sorted ylamine in 0.1 mL of dichloromethane The residue thus obtained is purified by chromatography on silica gel, eluent petroleum ether / ethyl acetate (9: 1) to give a white solid (mp = 58-60 ° C) with a yield of 98%. 1 H NMR (CDC1 ₃ , 400 MHz): 7.92 (d, 1 H, CTTarom, J≈ 2 Hz), 7.77 (dd, IH, CH arom, J≈ 8.2 and 2.2 Hz), 7.15 (d, IH, C_ETarom, J≈ 8.4), 7.14 (s, IH, C-ETarom), 6.85 (dd, IH, C-ETarom, J = 8 and 2.4 Hz), 6.51 (d, IH, C-ET arom, J≈ 8.4 Hz), 5.95 (dd, IH , C-ET-OPiv, J≈ 5.6 and 2.6 Hz), 4.74 (dt, IH, NC-ET ₂ , J≈ 14 and 4.1 Hz), 2.81 (ddd, IH, NC-ET ₂ , J≈ 12 , 10.1 and 2.1 Hz), 2.49 (s, 3H, Ar-C-ET ₃ ), 2.09-2.19 (m, 2H, N-CH2-C-ET2), 1, 67-1.82 (m, 2H, CH-C-ET ₂ ), 1.29 (s, 9H, C-ET ₃ ); ¹³ C NMR (CDCI3, 100 MHz): 177.2 (O-CO), 167.9 (N-CO), 147.7 (C-NO ₂ ), 141.8 (C-NH), 140.2 (C-CO), 137.64 (C-Cl), 137.4 (C-CH), 134.28 (C-CH3), 128.88 (CH arom), 128.0 (CH arom), 127 , 59 (CH arom), 125.26 (CH arom), 124.65 (CH arom), 121.0 (CH arom), 71.83 (CBP-OPiv), 46.6 (N-CH ₂ ), 39.14 (C- (CH ₃ ) ₃ ), 32.02 (N-CH ₂ -CH ₂ ), 27.33 ^* (3C, (CH ₃ ) ₃ ), 25.4 (CH-CH ₂ ), 20.23 (Ar-CH ₃ ); MS (ICP; m / z): 463 and 465 (MH '+ NHs), 446 and 448 (Mît), 342 and 344 (MH'-OPiv); IR (cm ¹ , CCL: 1735 (O-OO), 1659 (N-OO), 1529 (NO ₂ ), 1139 (0-00).

Example 22: 2-2-Dimethylpropionate of 7-fluoro-1- (2-methyl-4-metro-benzoyl> 2.3A5-tetrahvdro-1H-benzor & 1azepin-5-yle) Following a general method 6, a solution of 0.05 g (0.18 mmol) of benzazepine from Example 17 and 0.1 ml (0.076 g, 0.75 mmol) of triemyl-tmine in 1 ml of dichloromethane with 0.112 g (0.565 mmol) of 2-methyl-4-nitrobenzoyl chloride The residue thus obtained is purified by chromatography on silica gel, eluting petroleum ether / ethyl acetate (9: 1) to give a yellow oil with a yield of 97%. ^Α Η NMR (CDCI3, 400 MHz): 7.98 (d, 1H, Tarc-m, J≈ 2.4 Hz), 7.82 (dd, IH, C-ETarom, J≈ 8.6 and 2, 6 Hz), 7.22 (d, IH, CE arom, J≈ 8.8), 6.94 (d, IH, C-ET arom, J≈ 8.8 Hz), 6.63 (d, IH, CH arc-m, J ^≈ 5.2 Hz), 6.63 (s, IH, C-ET arom), 6.03 (dd , IH, CH-OPiv, J≈ 11.4 and 3 Hz), 4.81 (dt, IH, N CH ₂ , J ^≈ 13.6 and 4.2 Hz), 2.88 (td, IH, N - CH ₂ , J≈ 12.1 and 2 Hz), 2.56 (s, 3H, Ar-CH ₃ ), 2.16-2.25 (m, 2H, N-CH ₂ -CH ₂ ), 1 , 75-1.9 (m, 2H, CH-CH ₂ ), 1.36 (s, 9H, CH ₃ ); ¹³ C NMR (CDCI3, 100 MHz): 177.2 (O-CO), 168.04 (N-CO), 162.04 (d, IC, CF, ^ _C - _F = 248 Hz), 147.7 (C-NO ₂ ), 142.05 (CN), 137.58 (C- CO), 134.85 (C-CH), 129.38 (d, IC, CH arom, ² J _C - _F = 10 , 5 Hz), 127.54 (d, IC, CH arom), 125.22 (d, IC, CH arom, ² Jc- _F ≈ 4.2 Hz), 120.9 (CH arom), 120.2 (CH arom), 114.84 (C- CH ₃ ), 111.63 (d, IC, CH arom, ³ J _C -F = 28 Hz), 71.99 (CH-OPiv), 46.63 (N -CH ₂ ), 39.06 (C- (CH ₃ ) ₃ ), 32.15 (N-CH ₂ -CH ₂ ), 27.33 (3C, (CH ₃ ) ₃ ), 25.48 (CH- CH ₂ ), 19.89 (Ar-CH ₃ ); MS (ICP; m / z): 446 (MH '+ NHs), 429 (Mît), 326 (MH ^ -OPiv); LR (cm ^"1 , CC): 1735 (O- C≈O), 1659 (N-OO), 1529 (NO ₂ ), 1346 (NO ₂ ), 1139 (O-OO).

Example 23: 1- (4-Amino-2-methyl-benzoyl) -7-chloro-2.3.4.5-tetrahvdro-1H-benzo rfrlazepin-5-yl-2.2-dimethylpropionate A solution of 0.15 g ( 0.337 mmol) of the compound of Example 21 in 0.6 ml of ethanol and 0.2 ml of concentrated ΗCl at reflux are added 0.32 g (1.68 mmol) of SnCl ₂ . The reaction is heated at this temperature until the total consumption of the starting product (1 h 30). Then, the reaction is allowed to return to ambient temperature, the solution is basified by the addition of a saturated solution of Na ₂ Cθ ₃ , extracted with acetate

'• ^* ethyl, dried over Na ₂ SO, filtered and concentrated in vacuo. The residue thus obtained is purified by chromatography on silica gel, eluent petroleum ether / ethyl acetate (4: 1) to provide white crystals (mp = 185 -186 ° C) with a yield of 82%. 1 H NMR (CDCI ₃ , 400 MHz): 7.22 (s, 1H, C-ETarom), 6.93 (d, IH, CH arom, J = 8 Hz), 6.73 (d, IH, CH arom , J = 8), 6.56 (d, IH, CH arom, J = 8 Hz), 6.4-6.46 (m, 2H, CH arom), 6.22 (d, IH, CET arom, J≈ 8 Hz), 6.02 (d, IH, CH-OPiv, J≈ 7.4 Hz), 4.84 (d, IH, N-CH ₂ , J = 8.4 Hz), 3.7 (si, 2H, NH), 3.78 (t, IH, N-CH ₂ , J≈ 12 Hz), 2.37 (s, 3H, Ar-CH ₃ ), 2.05-2.21 (m , 2H, N-CH ₂ -CH2), 1.68-1.77 (m, 2H, CH-CH ₂ ), 1.35 (s, 9H, CH ₃ ); ¹³ C NMR (CDCI ₃ , 100.5 MHz): 177.07 (O-CO), 170.4 (N-CO), 147.14 (C-CO), 139.34 (C-NCO), 137 , 75 (C- Cl), 132.65 (C-NH ₂ ), 129.58 (CH arom), 128.71 (CH arom), 127.75 (CH arom), 125.57 (C-CH) , 124.22 (CH arom), 116.62 (CH arom), 114.32 (C-CH ₃ ), 111.88 (CH arom), 72.1 (CH-OPiv), 46.18 (N- CH ₂ ), 39.05 (C- (CH ₃ ) ₃ ), 32.05 (N-CH2-CH2), 27.32 (3C, (CH ₃ ) ₃ ), 25.56 (CH-CH ₂ ) , 20.1 (Ar-CH ₃ ); MS (ICP; m / z): 433 and 435 (MH ⁺ + NH ₃ ), 416 and 418 (Mît), 312 and 314 (MH ^ -OPiv); LR (cm ^-1 , CC): 3400 (NH ₂ ), 1734 (O-OO), 1651 (N- OO), 1142 (0-00).

Example 24: 2.2- Dimethylpropionate 1- (4-amino-2-methyl-benzoyl) -7-fluoro-2.3.4.5- tetrahvdro-1H-benzortilazepin-5-yl A solution of 0.054 g (0.130 mmol) of the compound of Example 22 in 0.3 ml of ethanol and 0.1 ml of concentrated ΗCl at reflux are added 0.124 g (0.654 mmol) of SnCl ₂ . The reaction is heated at this temperature until the total consumption of the starting product (1 h 30). Then, the reaction is allowed to return to room temperature, the solution is basified by the addition of a saturated solution of Na ₂ Cθ ₃ , extracted with ethyl acetate, dried over Na ₂ SO, filtered and concentrated in vacuo . The residue thus obtained is purified by chromatography on silica gel, eluent petroleum ether / ethyl acetate (4: 1) to provide a colorless oil with a yield of 78%. 1H NMR (CDC1 ₃ , 400 MHz): 6.95 (d, 1H, CH arom, J≈ 9.6 Hz), 6.73 (d, IH, CH arom, J≈ 8 Hz), 6.56- 6.66 (m,

2H, CH arom), 6.39 (s, IH, CH arom), 6.20 (d, IH, CH arom, J≈ 8.4 Hz), 6.03 (d, IH, CH-OPiv, J ≈ 10.4 Hz), 4.84 (d, IH, N-CH ₂ , J≈ 13.6 Hz), 3.71 (si, 2H, NH ₂ ), 2.77 (t, IH, N- CH ₂ , J≈ 12.2 Hz), 2.36 (s, 3H, Ar-CH ₃ ), 2.13-2.15 (m, 2H, N-CH ₂ -CH ₂ ), 1.69- 1.84 (m, 2H, CH-CH ₂ ), 1.34 (s, 9H, CH ₃ ); ¹³ C NMR (CDCI3, 100.5 MHz): 177.1 (O-CO), 170.53 (N-CO), 161.26 (d, IC, CF, _C - _F = 247 Hz), 150, 33 (C-CO), 147.0 (CH arom), 140.08 (C- NCO), 137.62 (C-CH), 129.93 (C-NH ₂ ), 128.46 (CH arom) , 116.5 (d, IC, CH arom, ² J _C - _F = 12.6 Hz), 114.44 (d, IC, CH arom, ² J _C - _F = 6.03 Hz), 112.17 (C-CH), 111.12 (C-CH ₃ ), 110.74 (d, IC, CH arom, ³ J _C. _F = 26 Hz), 72.24 (CH-OPiv), 46.19 ( N-CH ₂ ), 39.04 (C- (CH ₃ ) ₃ ), 32.17 (N-CH ₂ -CH ₂ ), 27.32 (3C, (CH ₃ ) ₃ ), 25.69 (CH -CH ₂ ), 19.34 (Ar-CH ₃ ); MS (ICP; m / z): 399 (MH), 298 (MHT'-OPiv); LR (cm ¹ , CCI4): 3487 and 3399 (NH ₂ ), 1734 (O- C≈O), 1649 (N-OO), 1148 (O-OO).

Example 25: Tolvaptan Following general method 6, treating a solution of 0.05 g (0.12 mmol) of the compound of Example 23 and 0.07 mL (0.048 g, 0.48 mmol) of triemylamine in 1 mL of dichloromethane with 0.046 g (0.301 mmol) of 2-methylbenzoyl chloride. Then, the crude product of the acylation reaction is dissolved in 1.5 ml of ethanol and 2 ml of a 2N NaOH solution are added to the reaction medium. The resulting solution is heated at 50 ° C for 2 hours. After allowing the reaction to cool, a few milliliters of water are added and the product precipitates. The crystals are drained, washed with cold water and recrystallized from methanol / ether to yield Tolvaptan with a yield of 85% over the 2 stages. The spectroscopic characteristics of this product correspond to those reported in the literature.

Example 26: Fluoro-Tolvaptan Following general method 6, a solution of 0.04 g (0.10 mmol) of the compound of Example 24 and 0.05 mL (0.04 g, 0.40) is treated. mmol) of txiethylamine in 1 mL of dichloromethane with 0.046 g (0.301 mmol) of 2-methylbenzoyl chloride. Then, the crude product of the acylation reaction is dissolved in 1 ml of ethanol and 1.5 ml of a 2N NaOH solution are added to the reaction medium. The resulting solution is heated at 50 ° C for 2 hours. After allowing the reaction to cool, a few milliliters of water are added and the product precipitates. The crystals are drained, washed with cold water and recrystallized from methanol / ethyl ether to give the title product (white solid) with a quantitative yield over the 2 stages.

Claims

1. Process for the preparation of at least one benzazepine compound of general formula (IA)

in which :

- R ¹ represents a halogen atom chosen from chlorine, fluorine, bromine and iodine, an alkyl, haloalkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl group, or else a hydrocarbon ring or a heterocycle, a polymer chain, a group - (CH ₂ ) _m -OR ^k , -CH (OR) (OR ¹ ), - (CH ₂ ) _m -SR ^k , - (CH ₂ ) _m -S (O) R ^k , - (CH ₂ ) _m -SO ₂ R, - (CH ₂ ) _m -Sθ2NR ^k R ¹ , - (CH2) _m -SO ₃ R ^k , - (CH ₂ ) _m -Nθ2, - (CH ₂ ) _m -CN, - (CH ₂ ) _m -PO (OR ^k ) (ORj, - (CH ^ -SiR ^ R " ¹ , - (CH ₂ ) _m -COOR ^k , - (CH ₂ ) _m - NCOR ^k , - (CH ₂ ) _m -NR ^k R ¹ , with: R ^k , R ¹ and R ^m each independently denoting a hydrogen atom or an alkyl, haloalkyl, acyl, aryl, alkenyl, arylalkenyl, alkynyl group, arylalkynyl, aralkyl, alkaryl, a hydrocarbon ring or a heterocycle, or else R ^k and R ¹ form, together with the atom to which they are attached, a heterocycle, with m denoting an integer greater than or equal to 0 , - n represents an integer chosen from 0, 1, 2, 3 and 4, with when n is greater than or equal to 2 ,. the corresponding R ¹ groups which may be identical or different, and where appropriate which may together form a hydrocarbon ring or a heterocycle,

- R ² , R ³ , R ⁴ , R ⁵ , R ⁶ and R ⁷ represent md in each other a hydrogen atom, a halogen atom chosen from chlorine, fluorine and bromine, an alkyl, haloalkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl group, or a hydrocarbon ring or a heterocycle, a polymer chain, a group - (CH ₂ ) _m -OR ^k , -CH (OR ^k ) (OR ¹ ), - (CH ₂ ) _m -SR ^k , - (CH ₂ ) _m - S (O) R ^k , - (CH ₂ ) _m -SO ₂ R ^k , - (CH ^ -SO ^ R ¹ , - (CH ₂ ) _m -SO ₃ R, - (CH ₂ ) _m -NO ₂ , - (CH ₂ ) _m - CN, - (CH ₂ ) _m -PO (OR ^k ) (OR j, CH ₂ ) m-SiR ^fc R ¹ R ^m , - (CH ₂ ) _m -COOR, - (CH ₂ ) _m -NCOR ^k , - (CH ₂ ) _m -NR ^k R ', with R, R ¹ , R ^m and m as defined above, or R ⁴ , R ⁵ , R ⁶ and R ⁷ form one by two one or more cycles (s ) hydrocarbon (s) or heterocycle (s), with at least one of the groups R ⁴ , R ⁵ , R ⁶ and R ⁷ representing a hydrogen atom, from at least one compound of general formula (LIA )

in which

Z ¹ represents a group chosen from: (i) alkyl, acyl, aryl, aralkyl, alkene or alkyne groups, hydrocarbon rings or heterocycles, (ii) a group -OR or - SR ^a in which R ^a is a group chosen from: - an alkyl, haloalkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl group, or a hydrocarbon ring or a heterocycle, or else a polymer chain; - a group -CR ^b R ^c PO (OR ^d ) (OR ^e ) in which: • R ^b and R ° each represent, independently of one another, a hydrogen atom, a halogen atom, an alkyl or perfluoroalkyl group, a hydrocarbon ring or a heterocycle, or alternatively a group -NO ₂ , -NCO, -CN, or a group chosen from groups of type -R ^f , -Sθ ₃ R ^f , - OR ^f , -SR ^f , -NR ^f R ^g , -COOR ^f , -O ₂ CR ^f , -CONR ^ ⁸ , -NR ^f COR ^g , in which R ^f and R ^g each independently denote an alkyl group, alkenyl, alkynyl, cycloalkenyl, cycloalkynyl, aryl, optionally condensed with a heterocycle, alkaryl, arylalkyl, heteroaryl, • or else R ^b and R ^c together form with the carbon atom to which they are attached a group C = O or OS or indeed a hydrocarbon cycle or a heterocycle; and • R ^d and R ^e each represent, independently of one another, a radical corresponding to one of the definitions given above for the group R ^f ; • or else R ^d and R ^e together form a hydrocarbon chain comprising from 2 to 4 carbon atoms, optionally interrupted by a chosen group p-trmi -O-, -S- and -NR ^h -; where R ^h meets one of the definitions given above for the group R ^f ; (iii) a group -NRW, in which: - R ¹ and R ^J , independently of one another, represent a radical chosen from an alkyl, haloalkyl, alkenyl, alkynyl, acyl, ester, aryl, arylalkyl, arylalkenyl group , arylalkynyl, or alternatively a hydrocarbon ring or a heterocycle; or - R ¹ and R ^J together form a hydrocarbon chain, comprising from 2 to 4 carbon atoms, optionally interrupted by a group -O-, -S-, or -NR ^H -, where R ^H corresponds to one of definitions given above for the group R ^f ,

R ^2a represents a group chosen from a hydrogen atom, a halogen atom, in particular fluorine, chlorine or bromine, an alkyl, haloalkyl, acyl, aryl, arylalkyl group, or else a hydrocarbon ring or a heterocycle, a polymer chain, a group - (CH ₂ ) _m -OR ^k , - (CH ₂ ) _m -SR ^k , - (CH ₂ ) _m -S (O) R ^k , - (CH ₂ ) _m - SO ₂ R ^k , - (CH ₂ ) _m -SO ₂ NR R ¹ , - (CH ₂ ) _m -SO ₃ R ^k , - (CH ₂ ) _m -Nθ2, - (CH ₂ ) _m -CN, - (CH ₂ ) _m - PO (OR ^k ) (OR ¹ ), in which R ^k , R ¹ , R ^m and m are as defined above and preferably a hydrogen atom,

- R ¹ and n are as defined above, comprising at least the steps consisting in: a- reacting said compound of general formula (IIA) with at least one olefin of general formula (A) in which :

R ⁴ , R ⁵ , R ⁶ and R ⁷ are as defined above, with at least one of the groups R ⁴ R ⁵ , R ⁶ or R ⁷ representing a hydrogen atom, to obtain at least one compound general formula (HIA) in which :

in which :

R ¹ , R ^2a , R ⁴ , R ⁵ , R ⁶ , R ⁷ and n are as defined above, c- transforming said compound of general formula (TVA) into at least its oxime derivative of general formula (VA)

in which :

R ¹ , R ^2a , R ⁴ , R ⁵ , R ⁶ , R ⁷ and n are as defined above, d- transforming said compound of general formula (VA) by a Beckmann rearrangement and consecutive reduction (s) ( s) in at least one compound of general formula (LA), and e- recovering said compound of general formula (LA).

2. Method according to claim 1, characterized in that said benzazepine compound corresponds to the general formula (LA) in which n = 1.

3. Method according to claim 2, characterized in that the group R ¹ is located in para position.

4. Method according to any one of claims 1 to 3, characterized in that the benzazepine compound corresponds to the general formula (LA) in which R ¹ represents a halogen atom, or an alkoxy group.

5. Method according to any one of claims 1 to 4, wherein said benzazepine compound corresponds to the general formula (LA) in which R ² and R ³ each independently represent a hydrogen atom or an alkyl group.

6. Method according to any one of claims 1 to 4, in which said benzazepine compound corresponds to formula (LA) in which R ² and R ³ each represent a halogen atom, and in particular of chlorine, fluorine or bromine.

7. Method according to any one of claims 1 to 6, characterized in that in the compound of formula (HA) Z ¹ represents -OR ^a , and in particuUer R ^a represents an alkyl group in Ci to Cι ₂ .

8. Method according to any one of claims 1 to 7, characterized in that the olefin of general formula (A) is disubstituted, and in particular cyclic or disubstituted terminal.

9. Method according to any one of claims 1 to 7, characterized in that the olefin of general formula (A) is monosubstituted, and in particular R ⁴ , R ⁵ and R ⁶ each represent a hydrogen atom.

10. Method according to any one of claims 1 to 9, characterized in that the substituent (s)) of said olefin of general formula (A) is (are) chosen (s) from -Oacyles groups and type groups - (CH ₂ ) pCN with p representing an integer varying from 1 to 10.

11. Method according to any one of claims 1 to 10, characterized in that the olefin of formula (A) is chosen from: vinyl pivalate, - allyl cyanide, and N-vinyl phthalimide.

12. Method according to any one of claims 1 to 11, characterized in that step a is carried out in the presence of an effective amount of at least one radical initiator, in particular dilauroyl peroxide (DLP).

13. Method according to any one of claims 1 to 12, characterized in that step b is carried out in an acid medium, in particular in the presence of camphorsulfonic acid.

14. Process for the preparation of at least one compound of general formula (LB)

in which: R ¹ , R ² , R ⁴ , R ⁵ , R ⁶ and n are as defined in claim 1 to 6,

X represents O, NR ⁹ , S, S (O), SO ₂ , SO ₂ NR ⁹ , and R ⁸ and R ⁹ independently of one another represent a hydrogen atom, an alkyl, haloalkyl or alkenyl group , alkynyl, acyl, aryl, arylalkyl, alkaryl, arylalkenyl, arylalkynyl, or a hydrocarbon ring or a heterocycle, a polymer chain, optionally substituted, or else R ⁸ and R ⁹ form together with the atom to which they are attached a heterocycle from at least one compound of general formula (TVB)

in which :

R ¹ , R ⁴ , R ⁵ , R ⁶ , R ⁸ , X and n are as defined above, and

R ^2a is as defined in claim 1 comprising at least the steps consisting in: a'- transforming said compound of general formula (TVB) into at least its oxime derivative of general formula (VB) in which :

R ¹ , R ^2a , R ⁴ , R ⁵ , R ⁶ , R ⁸ , X and n are as defined above. b'- transforming said compound of general formula (VB) by Beckmann rearrangement and subsequent reduction (s) into at least said compound of general formula HB), and c'- recovering said compound of general formula (LB).

15. Method according to any one of claims 1 to 14, characterized in that the step of preparing the oxime derivative of formula (VA) or (NB) comprises bringing said compound of general formula (LVA) into contact with ( IVB) with an effective amount of nitromethane or hyckoxylamine.

16. The method of claim 15, characterized in that it further comprises a step of recovering the product of formula (VA) or (VB), in particular by recrystallization.

17. Method according to any one of claims 1 to 16, characterized in that the transformation of the compounds (VA) or (VB) by Beckmann rearrangement is carried out in the presence of an effective amount of PC1 ₅ .

18. The method of claim 17, characterized in that the PCI ₅ is used in molar excess relative to the compounds of formulas (VA) or (VB).

19. Method according to any one of claims 1 to 18, characterized in that the product resulting from the Beckmann rearrangement is reduced by an effective amount of at least one metallic reducing agent, in particular zinc.

20. The method of claim 19, characterized in that the reduction product obtained is treated with an effective reducing amount, in particular of BH ₃ , and in particular of BH ₃ .THF.

21. Method according to any one of claims 1 to 18, characterized in that the product resulting from the Beckmann rearrangement is treated with an effective amount of NaBH *. 22. Compound of general formula (IA)

in which :

R ¹ represents a halogen atom chosen from chlorine, fluorine, bromine and iodine, an alkyl, alkenyl, alkynyl, acyl, aryl, arylalkyl, arylalkenyl, arylalkynyl group, or else a hydrocarbon ring or a heterocycle, a polymer chain, a group - (CH ₂ ) _m -OR, -CH (OR ^k ) (ORj, - (CH ₂ ) _m -SR ^k , - (CH ₂ ) _m -S (O) R ^k , - ( CH ₂ ) _m -SO ₂ R ^k , - (CH ₂ ) _a - SO ₂ NR ^k R ¹ , - (CH2) _m -SO ₃ R, - (CΗ ₂ ) _m -NO ₂ , - (CH ₂ ) _m -CN, - (CH ^ -PO ^ R ^^ R ¹ ), - (CH ₂ ) _m - SiR ^ R " ¹ , - (CH ₂ ) _m -COOR ^k , - (CH ₂ ) _m -NCOR ^k , - (CH ^ -NR ¹ ^ ¹ , with R, R ¹ , R ^m and m as defined in claim 1, R ² , R ³ , R ⁴ , R ⁵ and R ⁶ are as defined in claims 1 to 6 , R ⁷ = -XR ⁸ , XR ⁸ being as defined in claim 14, n = 1. 23. Compound according to claim 22, characterized in that it is chosen from:

- 2,2-dimethyl-propionate of 7-chloro-2,3,4,5-tetrahydro-1H-benzo [b] azépin-5-yl, - 2,2-dimethyl-propionate of 7-fluoro- 2,3,4,5-tetrahydro-lH-berιzo [b] azepin-5-yl,

- 7-methoxy-2,3,4,5-te1 „rahydro-1H-benzo-azepin-5-yl 2,2-dimethyl-propionate,

- (7-fluoro-2,3,4,5-te1rahy (-j: o-1H-benzo |] azépm-5-yl) -acetom ^' trile, and

- 2,2,7-dimethyl-propionate of 3,3,7-trichloro-2,3,4,5-tetrahydro-1H-benzo [b] -azépin-5-yl, and - their derivatives. 24. Compound of general formula (VB) in which :

R ¹ , R ^2a , R ⁴ , R ⁵ and R ⁶ are as defined in claims 1 to 6, XR ⁸ is as defined in claim 14 and n = 1. 25. Compound according to claim 24, characterized in that 'It is chosen from: - 4-2,2-dimethyl propionate - [(E) -hy (hoxyimino] -7-chloro-1,2,3,4-tetrahydro-naphthalen-1 -yle, - 2 , 2 4 - [(E) -hydroxyimino] -7-fluoro-1,2,3,4-tetrahydronaphthalen-1-yl dimethyl propionate, and - 2,2 - 4 - [(E) -hydroxyimino dimethyl propionate ] -7-methoxy- 1,2,3,4-tetrahydronaphthalen-1 -yle, and - their derivatives 26. Process for the preparation of benzazepine of general formula (VIA):

in which :

R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and n are as defined in claim 22, and R ¹⁰ represents a hydrogen atom, an alkyl or acyl group, and in particular a group methyl, comprising at least the transformation of a compound of general formula (HA) into a compound of formula (IA) according to the method according to any one of claims 1 to 21. 27. Process for the preparation of benzazepine of general formula (VLB) :

in which :

R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , XR ⁸ and n are as defined in claim 22, and

R ¹⁰ represents a hydrogen atom, an alkyl or acyl group, and in particular a methyl group, comprising at least the transformation of a compound of general formula (TVB) into a compound of formula (LB) according to the process according to any of claims 14 to

21.