3-hydroxy-1,4-benzodiazepine-2-ones

or enhanced exobarbital action, and is therefore highly active.

Pantanassis 5, 151 25 - Paradise of Maroussi

REF .: S 17821 SH

3_3_3_ϊ_Γ _? _ Ή _? _ Ϊ_3-2.3 _____ L3_9_iL3JL3_ £

GEROT-PEARKAZEUTIKA GESELLSCHAFT MBH, company based in ARNETHGASSE J,

1171 VIENNA, Austria.

Ϊ-Ξ50Δ0Σ ΠΑΡΑΕΚΣΙΗΖ ΝΕΩΝ 5-ΪΔΡ0ΞΪ-1Λ-ΒΕΝΖΟΔΤΑΖΕΙΔΙΝ-2-0ΝΩΚ

<img file="GR73901B_D0001.tif" />

CLAIMS

1. Process for the preparation of 3-hydroxy-1,4-benzoiazepine-3-ovOv of the generic type

<img file="GR73901B_D0002.tif" />

OH (I)

<img file="GR73901B_D0003.tif" />

2. Process for the preparation of 1- (2-cyanoyl) -7-chloro-3-hydroxy- (2 '- &lt;? Thoro- .phenyl) -1, p-d-Doro-2H-1,^ί+ -benzoiazepine-2-δνης.

3. 1 (preparation of 1- (2-blue thio) -? - chloro-3-hydrozy-5- (2 * -chloropsa&gt; .nyl) -1, J-di nororo-2H-1, * + ν-2-one.

4. Method for the preparation of 1- (2-methoxy. 6-yl) -7-chloro-3-hydroxy-5 - '? Aynyl1,5-dihydro-2H-1,4-benzodiazepine-2-dne.

&gt;. Method of preparation 1- (2-cyanomethyl) -7-chlorop-3-hydroxy-5-phenyl-1,3-dioporo-1,1-benzodiazepine-2-6n.

6. Method of preparation of 1- (2-cyanethyl) -7-nitro-3-hydroxy-5-phenyl1,5-di. Term - 22-1,4-vezodiazepine n-2-one.

7. of the preparation of 1- (2-cyanadyl) -7-u.tro-3-yroxy-5- (2'-chlorophenyl) -1,3-dihydro-2R-1,4-benzodiazepine n-2 -δνης. -δ. Method for the preparation of 1- (2-cycloyl) -7-nitro-3-hydroxy-5- (Z'-fluorophenyl) -1,3-dihydro-2H-1,4-benzodnazepine-2-dne.

<img file="GR73901B_D0004.tif" />

5a v 1, characterized in that 3-hydroxy-1,4-benzodiazepine n-2-is the general formula

<img file="GR73901B_D0005.tif" />

where the B₁ and B 'have the above significance, or those with alkali compounds thereof, react if desired by the use of basic substances and / or tf by the addition of transfer catalysts by phases, as quaternary salts of ammonium or phosphonium or coronet, possibly alkyl iodides, with compounds of the general formula

CH- -CH - B (III)

I² I

X iaou td B has the above meaning, td X represents the active group as e.g. Allogeneic or sonolphonyl group, xui τδ Υ hydrogen or in the case where δ = θλ τδ X together with τδ Υ can form a second bundle, where the compounds of the general type III can simultaneously be useful or dilute with an inert solvent.

10. Process according to Claim 9, characterized in that the reactants of formula III are: 2-methoxy-ethyl chloride, 2-methoxy-ethyl bromide, jj-chloropropion trillium or 3-bromo-propyl.

11. Method according to claim 9 with the characteristic κδν that as opposed; ρδν ·.

A component of formula III is acrylonitrile. * '

<img file="GR73901B_D0006.tif" />

A 4 * 2 invention relating to a novel 3-hydroxy-1,4-benzodiazepine-2-one of the genotype type:

Mrs.

<img file="GR73901B_D0007.tif" />

CH 2 in a method for their preparation.

These novel compounds of formula I contain an asymmetric carbon atom and can therefore be cleaved according to standard methods in the stereoisomeric compounds.

The method 5 invented is that 3-hydroxy-1,4-benzodiazepine-

<img file="GR73901B_D0008.tif" />

II where the 3 ^ and R ^ have the above meaning, they are selectively substituted in 173, while 02 in position 3 remains unaffected.^Ζ

The novel compounds of general formula I are pharmaceutically useful compounds, which are indicated for low toxicity by their potent sedative and hypnotic or esobarital properties, and may also be used as new medicinal products.

X-rays of general type I, in which R⁼ COH ^ or CR have not been described. Such derivatives I, in which R represents other c-groups are usually obtained by substituting 4-oxide θέ at position 1 instead of / · / ';

<img file="GR73901B_D0009.tif" />

- 5 δράσιν POLONOVSKY αύτοΰ πρδς τδ 3-ακυλοζυ-παράγ «γον και ίν συνεχείς σαΐωνοποίησιν (DS-OS 2 237 211, ARZKEIK.FORSCH, 25, 72C (1975)).

Compounds of general formula II are known since 1962. P._aρ * ολον τοΰτο δέν εγινεν μέχτι τοϋδε ου'εμία χρήσις τής δύνατητος μιδς έκλεκτικής υποκατατάσεις είς το ΧΗ. Easily accessible compounds by the invented method, e.g. oxazepime, lorazepam etc. (cf. AT-PS 309 436) New, high-performance hypnotic hypnotics are obtained.

According to the method, 3-hydroxy-1 / i-benzodiazepine-2-ss of the general formula II virus react with alkali compounds thereof, if desired by the use of basic compounds and / or by the addition of phase transfer catalysts, in stages. ammonium or phosphonium or coronethers and possibly alkyl iodides, with compounds of the general formula

CE- - CH - Β »² I (III) 'wherein τδ R has the above meaning, τδ X represents an active group as e.g. αlogdon or sulfsnyloxy-dmas, and τδ Υ means hydrogen, or in the case where- 2 = Ci. ', X together with Υ may form a second bond, * 2ς opposite components of general type III are suitable .χ. the

2- methoxyethyl chloride, 2-methoxyethyl bromide or acrylonitrile, as well as

3- chloro-prop. P. Trillion or 3-bromo-propionitrile.

Until now also do not describe compounds with alkalis of the first 6 λ $ «with τδν general type II are obtained e.g. readily by reacting these compounds with an equal amount of potassium tert-butyl tertiary in absolute solvents as dioxin. Before the second the raw material (is crushed and continuously precipitated or after potassium compound or can be obtained by precipitation with water.

In the experiment, of the reaction of the compounds thus obtained with alkalis

<img file="GR73901B_D0010.tif" />

- 6 (II) with one;, compound X-CHg-CHg-O-CHj, where τδ X has the above signal di if, received by; in the case, according to which R ^ = ortho-analog, 2-equals, however, do not correspond to the structure of I (with B = OCHj); POLONOVSKY via N-oxide during hydrolysis of 1- (2-methoxy-thyl ^ -2-acetozy-5- (o-halo-phenyl) -cranks

It is therefore surprising that from compounds with alkalis of II, in graves which let Rd yn mean ortho-halogen, when reacted with XCH ^ CH ^ -O-CHj according to the method found are readily obtained and in good condition &lt;

compounds of formula I with R = 0CH ^.

It is also further surprising or possible for the selective cybanyethylation of compounds of formula II in the amide atom K (position 1), e.g. The acetanilide which corresponds to this structure reacts accordingly to the invention at 90-100 ° C with acrylonitrile; 033.REACTIONS 5 »88,89 (19 ^ 9); In acrylonitrile it is offered in large excess as a reaction medium.

The density of the groups -CH ^ -CH ^ -R in the amide atom K can be shown by the coupling signals λ ch-OH in the NMR spectra of the obtained production, and by the esterification of the free

For the following examples or backup it is clarified more closely, but without being limited to these. Temperature data are reported in degrees Celsius.

EXAMPLE 1 *

In suspension 10 g. 7-x 2H-1, ^ - benzoiazepine-2-dnis or hour-3-yr y-5- (2'-fluoro-phenyl) -1,3-di Poro-

<img file="GR73901B_D0011.tif" />

- 7-triethyl-benzyl-ammonium chloride (TEBA) is then added without stirring 8 drops in 4% methanolic hydroxide solution of benzene-trimethyl-ammonium (TBITOK B). After stirring at room temperature the mixture is allowed to stand overnight at 4 °, the precipitate is filtered off, washed with acetone and recrystallized from ethanol. Thus obtained 1- (2-cyano-ethyl) -7-chloro-3-hydroxy-5- (2'-fluoro-phenyl) -1, β-dihydro-2H-1,4-benzod&gt; azepine-2 -dni, melts at 190-3 °.

* Without the addition of TEVA is also formed or substituted 1- (2-cyanoyl) -7-chloro-3- (2-cyanethozy) -5- (2'-fluorophenyl) - !, 3-dihydro-2H-ΐ1,4- benzodiazepine-2-sne, or which after recrystallization from CH ^ CN at 204-7 °.

For separation of the mono- and the substituted product from the starting material in a thin layer, Si ^ 6F F 254 can be suitable as eluent for the benzene / dioxide / acetic acid mixture (90: 25: 4 parts by volume).

PA? ΑΩΕΙΓΚΑ__2 'In suspension 10 gr. 7^-chloro-5-hydroxy-5- (2'-chloro-phenyl) -1,3-hehydro2B-1,4-benzoiazepine-2-dne (lorazepam) in 50 ml. acrylonitrile is mixed with 1 g. TEA and S drop in a 4%% methanolic methanolic solution and stir for 24 hours at room temperature. A_αΧAfter the mixture is cooled to 4 °, the precipitate is filtered off and recrystallized from ethyl ester. thus obtained or 1- (2-cyano-yl) -7-chloro-3-hydrozy-5— (2'-chloro-phenyl) -1,3-dihydro2H-1,4-benzodiazepine y-2-dne, or which melts at 19S-202 ° C.

Without the addition of TEVA is formed or substituted 1-L2-cyano: Psylo) 7-chloro-5- (2-cyano-oxo) -5-L2 '-chloro-phenyl) -1, β-dihydro -2H'-1,4-benzo i i azepi v2-dne with m.p. 210-3 °. (apd CHjCK).

EXAMPLE 3 gr. of the potassium compound of 7-chloro-3-hydroxy-5-phenyl-1,3-ciporo

<img file="GR73901B_D0012.tif" />

j

- · Ί

-2E-1,4-benzodiazepine-2-dne (dzazepam) are dispersed in 340 ml. 2-Methoxy-thiol chloride followed by addition of 6 g. TEBA, ALIQUAT and NAJ are heated at room temperature for 20 minutes at 50 ° C and then for 15 hours at 4 ° C. The slurry was evaporated to room temperature, the oily residue was dissolved in CHBl3 and quenched several times with E. coli. The CHCl3 solution was dried over Ka ^ SO ^, filtered, evaporated and the residue taken up in CCl ^, when crystallizing the substance. After acrystallization from isopropanedine or diisyl ethyl ester is obtained either 1- (2-methoxy 6-yl) -7-chloro-5-hydroz-5-phenyl-1,3-hydro-23-1, 4-benzodiazepine-2-dne , ύς άχρους κδνις, σ.τ. 1 ° C - 161 °.

* The starting material used after the potassium compound is obtained by heating for 1 hour in a mixture of 6 g. δξαζεπάμης with 24.9 g. tertiary Butyl potassium in 6 ml ml. Absolute diozane is stirred at 75 °; First it is dissolved, then it is precipitated in a large crystalline precipitate. The filter is filtered off, overnight in the refrigerator, washed with isopropyl ether and dried in vacuo. Σ.τ. 192-7 ° (dec.).

EXAMPLE__4 &lt;

In suspension 20 g. δξαζεπάμης εις 240 κ.εκ. acrylonitrile is reconstituted dropwise with stirring with 3 ml. in TRITC '-.- B 4θ% methanolic solution and then heated for 50 hours at 50 °, when an orange solution is formed. After staying overnight the reaction is over. The solution is concentrated in vacuo, and when the concentrate is cooled. in Gzima, which is recrystallized by CHC3-. It is melted at 192-4 ° -.and consists of n 1- (2-cyano) -7-chloro-3-hydroxy-5-phenyl-1,3-dihydro-2X-1,4-benzodiazepine, - 2-ονην.

If the mixture is heated for 2 hours at 50 °, it is also formed and the substituted 2-cyanethyl) -? - chloro-3- (2-cyano-6-oxy) -5-phenyl-1,3-dihydro-2E1, 4-benzodiazepine-2-δ, which is practically crystallized: απδ CH ^ CN melts at 215-8 °, ·; '· τ · ϊ ·

<img file="GR73901B_D0013.tif" />

<img file="GR73901B_D0014.tif" />

2Δ? Αδειγκα__5

In suspension 2 g. lorazepam in 20 ml. of acrylonitrile after addition of 0.1 g. TEVA and 1 ml. triethylamine is heated under stirring to 50 °. Forms a pale yellow solution, then gradually forms a precipitate. After 3 hours the mixture is concentrated in vacuo and the concentrate is stirred overnight to crystallize at 4 °. The precipitate is filtered off, recrystallized from ethyl acetate and identical to the excipient 2 obtained mono-substituted product (m.p. 19θ-202 °).

In the previous examples the following news are also taken (

compounds:

1- (2-cyanothyl) -7-ni-tro-3-Hydrosy-5 "nyl-1,3-dihydro-2δ-1,4-benzodiazepine n2-one, m.p. 105-8 °.

1- (2-Cyanyl) -7-nitro-3-hydroxy-5- (2 * -chloro-phenyl) -1,3-dihydro-2H-1,4-benzodiazepine v-2-one, m.p. 191- ^ °

1- (2-cyano-yl) -7-nitro-3-hydroxy-5- (2 * -fluoro-phenyl) -1,5-dihydro-2H-1, or-benzoiazepine-2-one, p .τ. 183-6 °.

ΠΕΡΙΑΗΥΙΣ

3-yroxy-1,4-benzodiazepine-2-s of the general formula

<img file="GR73901B_D0015.tif" />

δδ τδ Ε ^ είναι δρθο-όλογδνον, δεικνύουν μίαχυχυΡΕς ήρεμιστικην και έπιμηχύνουσαν τδν ύπνον δρόσιν ή ένι σχυουσαν την έξοβαρβιτάλην δρόσιν, και είναι δθεν ύπνατιχδaz highly highly active.

ΕΣ »_»

In

Athens, τζ 6ρ 'Ιουνίου 19δθ * 0 Plenipotentiary Lawyer

<img file="GR73901B_D0016.tif" />

<img file="GR73901B_D0017.tif" />

Resonance in A. &amp;.

Athens k ^ -S -__ 1 »

TMHMATAPXH1

<img file="GR73901B_D0018.tif" />

AUSTRIAN INVENTORY OFFICE

WIEN 1, .KOHLMARKT 8-10 'No.Fachelou: A 9031/78

It is hereby certified by the Austrian Patent Office that the company GEROT PHARMAZEUTIKA GESELLSCHAFT M, B.H., based in WIEN XVII. hydroxy-1,4-benzodiazepine-2-cod.

and that the attached description agrees with the Originally deposited after the statement of that description.

Austrian Patent Office Vienna, 29 November 1979 * 0 President Signature: WITTMANN (TS)

<img file="GR73901B_D0019.tif" />

The invention relates to a process for the preparation of novel 3-hydroxy-1,4-benzodiazepine-2-one of the general formula

<img file="GR73901B_D0020.tif" />

OH (I) δδ τδ H represents methoxyl or CN, τδ Β₁ hydrogen, halogen, CF ^ or EOg^χοί το ϊ? 2 hydrogen or horse, provided that τδ Β does not mean methosyl, when τδ Ε2 is ortho-halogen.

The method of the invention comprises that 3-hydroxy-1,4-benzodiazepine 2-is of the general formula

<img file="GR73901B_D0021.tif" />

CH - OH (ΤΟ τδ ΝΗ, ένέ τδ ΟΗ είς την θέσιν 3 μένει ανπηρεαστος.

The novel compounds of general formula I are pharmaceutically useful compounds, which are indicated for low toxicity by strong sedative and hypnotic or exobarbital-enhancing properties, and may also be used as intermediates for new medicinal products.

Compounds of general formula I, of which CN = BH are not described. Such derivatives I, to which the other groups B are usually obtained by substituting the substituted U-oxide, are opposed.

<img file="GR73901B_D0022.tif" />

actin POLOKC '. 1962 - Hop'iSXov has so far made no use of the potential for selective substitutions in the NK. By the method invented readily available compounds, e.g. dzazepam, lorazepam, etc. (cf. AT-PS 309 ^ 36) New hypnotic new hypnotics are obtained by reacting one raisin.

According to the method of the invention, 3-Dioxy-4, 4-benzodiazepine-2-2 of the general formulas II or their alkali compounds are reacted, if desired by the use of basic compounds and / or by the addition of phthalate catalysts. quaternary ammonium or phosphonium salts or crowns and possibly alkyl iodides, with compounds of the general formula

CH_ - CH - Β (III) •^a «

Ύ. Where τδ E has the above meaning, τδ X represents a functional group as e.g. άλογδνον η σουλψ;

2 Reactive components of general formula III are suitable, e.g. the:

2-mesoxyethylene chloride, 2-methoxy-ethyl bromide or acrylonitrile, and 3-x *;

Until now also do not describe compounds with alkalis of the first&gt; all with the type II type are obtained e.g. easily by reacting these

I: compounds with a potassium tri-butyl potassium compound in absolute solvents such as dimethylformamide or diosane. Prior to this the starting material is dissolved and then continuously precipitated or after potassium compound or can be obtained by precipitation

Ras

In the reaction experiment

<img file="GR73901B_D0023.tif" />

(Il) with a cvuoiv X-CH₂-CE2 “0-CHj, where τδ X has the above meaning, are taken as 6: 2 in the case, after the expression S₂ = ortho-analog, 2-isomers, which therefore do not correspond to the structure of I (with R = OCHj). These isomers obtained;. also in the usual SOL POLONOVSKY via N-azide to hydrolyze tBV1-i2-methoxy-thyl) -3-acetoxy-5- (O-halophenyl) -x

It is therefore surprising that compounds with alkalis of II, in which td does not mean ortho-halogen, have a reactive reaction, with the XCH.CE ^ -O-CH in the e-, wide-ranging method are easily obtained while in good condition. of type I with B = OCH ^.

Furthermore, it is also surprising or possible for the selective synthesis of compounds of formula II in the amide atom K (position 1), because e.g. The acetanilide, which corresponds to the structure herein, reacts accordingly to the invention primarily at 9 ° -1OO ° C with acrylonitrile, or reacts with a secondary temperature already below or at a temperature below the alkoda temperature. 5, 88.89 (19I)).^Kaccording to the invented method; the reaction takes place in the amide atom N of_ΧSI) already at room temperature, without simultaneously substituting at OH, while acrylonitrile is offered in large excess as a reaction medium * Substitution of the -CH groups₂-CH₂-R in the amidic N atom can be shown by the CH-OH coupling signals in the NMR spectra obtained from the derivatives, and by the esterification of the free OHs.

&lt;

For the following examples, the invention will be further clarified, but without being limited thereto. Temperature data are reported in each case in Belsius valleys.

ΠΑΡΑΔΒΙΓΚΑ__1 - ··, -In suspension 10 gr. 7-x-hour-3-hydroxy-5- (2 * -fluoro-phenyl) -1,3-dihydro2K-1 L-benzodiazepine n-2-one in 50 ml. acrylonitrile is mixed with&gt; 1 g of triethyl-benzyl-ammonium chloride (TEBA) then added in 8-drop concentrations in a methyl solution of a hydroxide solution of benzyl chloride The mixture is left overnight at ^ °, the precipitate is filtered off, washed with acetone and recrystallized from the ethane. There was thus obtained 1- (2-cyanethyl) -7-chloro-3-i-rosu-5- (2'-fluoro-phenyl) -1,3-d: hydro-2H-1, D-benzodiazepine-2 -dni, melts at 190-3 °.

Without the addition of TE3A is also formed or substituted 1- (2-cyano) thyl) -7-chloro-3- (2-cyanethozy) -5- (2'-fluorophenyl) -1,3-dihydro-2K-1, e.g. -benzodiazepine-2-δN, or which after recrystallization from CH ^ CN melts at 2A-7 °.

For the separation of the mono- and di-substituted product from the starting material in a thin layer, SiOg 6F F 25¼ and eluent benzene / dioxane / ozonic acid mixture (90: 25: ¼ vol. 10 gr. 7-x '; h-3-hydroxy-5- (2'-chlorophenyl) -1,5-dihydro-2H1, z-benzodiazepin-2-one (lorazepam) in 50 ml. acrylonitrile is mixed with 1 g. ACIDS and 8 drops in a medium solution of TRITON E * 0 is and stirred for 2 hours at room temperature. The mixture is then cooled to 4 °, the precipitate is filtered off and recrystallized from ethyl ester. There is thus obtained either 1- (2-cyano-yl) -7-chloro-5-hydroxy-5- (2 * -chloro-phenyl) -1, '- dihydro2E-1, D-benzodysepine-2-dne, or whichever melts at 19 ° -2 ° C.

^ Unrepresented TEVA is formed by either substituted 1- (2-cyanidyl) -7chloro · p-3- (2-cyst -: δ o z u) -5 - '' 2 '-x / .hour-phenyl) -1,3-ahydro-2H-1, D-benzodiazepine V2-δ with m.p. 210-3 ° (mp CH ^ CN).^: of the potassium compound of 7-space-3-hydroxy-5-phenyl-1,5-

<img file="GR73901B_D0024.tif" />

-2H-1,4-benzodiazepine-2-dne (dzazepam) are dispersed in 3 ^ 0 ml. 2-methoxy-ethyl chloride and then added per 6 g. TXBA, ALIQUAT and KAJ are heated under stirring for 20 hours at 50 ° and then for 15 hours at 4 °. The mixture is evaporated in vacuo, the oil wells are dissolved in CHCl ^.^Mrs.^ άνακινεΐται πλειστάκις με Ε ^ Ο. The CHOI διά solution is dried over Na ^ SO., Filtered, evaporated and the residue taken up in CCl ^ to crystallize the substance. Following the recrystallization from isopropanthylene or ethyl oxylate, 1- (2-methyl-thyl) -7-chloro-3-y &amp; rosy-5-nyl-1,3-dihydro-2H-; -βεν ζοδιαζεπιν-2-δνη, 1 · ς άχρους κδνις, σ.τ. 16 ° -1 °.

The starting material used after the potassium compound is obtained by heating for 1 hour in a mixture of 6 g. ozazepan with 2 g. tert-b, potassium onylate to 600 ml. Absolute dioxin is stirred at? 5 °; First it dissolves, then it settles in a large crystalline precipitate. It is filtered, after being left in the refrigerator overnight, rinsed with isopropyl ether and dried in a vacuum. Σ, τ. 192-7 ° (dec.).

EXAMPLE ^

Xn suspension 20 g. δζαζεπάμης εις 2 ^ + 0 κ.εκ. acrylonitrile is mixed dropwise with stirring with 3 ml. of a methanolic solution of TBITCJ.-3 ° C and then heated for 1 hour at 50 °, when an orange solution is formed. After staying overnight the reaction is over. The solution is concentrated in vacuo, and during the cooling of the concentrate is taken to precipitate, where it is refluxed by CHCl. ) -7-chloro-5-hydroxy-5-phenyl-1,3-dihydro-2l'-1,^ίibenzodiazepine-2-sv.

* If the mixture is heated for 2 hours at 50 °, it is also formed by the addition of 1- (2-cyano-yl) -7-chloro-3- (2-cyanethozy) -5-nyl-1,3 "dihydro-2B -

<img file="GR73901B_D0025.tif" />

- 7 π · 5? Example__5

Good suspension 2 g. lorazepdm in 20 ml. acrylonitrile after addition 0.1 g. TEVA and 1 ml. triethylamine is heated under stirring to 50 °. It is formed in a pale yellow solution which gradually forms in the precipitate. After 3 hours the mixture is concentrated in vacuo and the concentrate is allowed to crystallize overnight at 4 °. The precipitate is filtered off, recrystallized from ethyl ester and is identical to the present. 2 mono-substituted product obtained (m.p. 198-202 °).

The following examples are also taken from the following new compounds:

1- (2-cyano) -7-nitro-3-hydroxy-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepine n2-one

- (2-cyano-female) -7-nitro-3-hydroxy-5 ~ (2 * -chloro-phenyl) -1,3-thihydro-2H-D, 4-benzodiazepine-2-dne - (2-cyan yes type) -? - nitro-3-hydroxy-5- (2'-fluoro-phenyl) -1,3-dihydro-2X- ', 4-benzodiazepine-2-dne

- (2-cyano-yl) -7-trifluoromethyl-5-water pink y-5-phenyl-1,3 ~ 6hydro-2H-1 nzodiazepine-x-dne.

<img file="GR73901B_D0026.tif" />

Α_Ξ_Ι_Ω_Σ_Ε_Ι_Σ

1. Method for the preparation of novel ^ -hydroxy-1, 4-benzodiazepine n-2-cods;