CA1041500A - 5-aryl-pyrido-(b-6,7)-1,4-diazepines having a wider annuelated hetero cycle - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
The present invention provides a compound having the general formula

Description

10~5V0 The present invention relates to 5-aryl-pyrido-(b-6,7)-1,4-diazepines and the pharmaceutically acceptable salts having pharmacodynamic properties.
In particular the present invention provides 5-aryl-pyrido-tb-6,7)-1,4-diazepines having the general structure /N \

,Y \ ~ I

Cl ~ R2 ' wherein Rl represents an alkyl group containing 1 to 6 carbon atom~
; and R2 represents hydrogen or a halogen atom, and their pharma-ceutically acceptable salts.
The halogen atoms are, for example, chlorine, fluorine, ~ bromine, particularly chlorine or fluorine. The lower alkyl group j preferably contains 1 to 4 carbon atoms, particularly 2 or 3 carbon atoms. Examples of such lower alkyl groups include methyl, ! ethyl, isopropyl, n-butyl, t-butyl, n-hexyl, and isobutyl. The compounds having the formula I may also be in the tautomeric form in which a hydrogen of the diazepine -CH2 group is at the nitrogen atom in the 3 position or at the carbon atom in 6 position while the double bonds are correspondingly shifted. The compounds can be partially or entirely in one of the possible tautomeric forms.
Under standard conditions of operation and storage there usually i is an equilibrium.
The compounds according to the invention have valuable pharmacodynamic properties and a particular they have sedative and marked psychosedative, anxiety-relieving and spasm-relieving i 30 , . . , . ~ :
- , ., ~ , .
~ . . , . :

~ ~ ' ' - . ,' :

104~5(~0 properties. To some extent the compounds also act as anti~
phlogistics.
The compounds according to the invention can be pro-duced in a conventional manner in particular a compound having the general formula X

1- ~ CH2 II
C ~,~/ " ' ~R2 .-. . .
wherein R2 is as above and X represents oxygen, sulphur, imino a benzyl-imino group or in its tautomeric form X may be an alkyl-thio or alkoxy group containing 1 to 5 carbon atoms or an alkyl or dialkyl-amino group in which the alkyl radicals containing 1 to 6 carbon atoms, is reacted with a compound having the formula N2N - NH - CORl III

wherein Rl has the above meaning, and is simultaneously or subsequently cyclized to the compound having the formula I.
The process can be carried out as a melt, in a solvent or in a dispersing agent at temperatures between 0 and 250C, preferably between 50 and 160C. For example, glacial acetic acid, aliphatic alcohols such as ethanol, butanol and hexanol cycloalkanols such as cyclohexanol, dioxane, tetrahydrofuran, dimethylsulphoxide, dimethylformamide, alphatic ethers chloro-form, hydrocarbons such as toluene, xylene, benzene, chloro-hydrocarbons such as chlorobenzene, ethers such as diethylene glycol dimethyl ether or diethyl ether or amides such as N,N,N ,N ,N",N:-hexamethyl phosphoric triamide, are suitable as 30 solvents or dipersing agents. If required, condensing agents such as polyphosphoric acid, polyphosphoric ester, sulphuric ., . . - .~ . ~ ., . . - .

- - ' :. ::... - - ~ . .. ' . , 104~5W
acid, zinc chloride, pyridine, pyridine salts or tertiary amines may be added.
When X in formula II represents an alkylthio group, alkoxy group or dialkylamino group, the compound having the formula II is in its tautomeric form, which is based on the structure XH
-N = C -For the other meanings of X there can also be corres-ponding tautomeric forms or tautomeric equilibria. This is immaterial insofar as the reaction in the process is concerned.
As lower alkylthio or alkoxy groups X preferably represents the methylthio or ethylthio group or the methoxy or ethoxy group.
These groups can be activated by a substituent. These activated groups are, for example, the o- or p-nitro-benzylthio or the o- or p-nitro-benzyloxy group. As a mono-substituted amino group X represents particularly a lower alkylamino group such as the methyl-amino group or an aralkyl-amino group, such as the benzyl-amino group. As a disubstituted amino group X represents a lower dialkylamino group such as the dimethyl-amino group.
Basic compounds having the general formula I can be converted into the pharmaceutically acceptable salts by conven-tional methods. The known and therapeutically applicable acid radicals are suitable as anions for these salts. Examples of these acids are sulphuric, phosphoric acid, hydrohalic acids, ; ethylene-diamine tetraacetic acid, sulphamic acid, benzosulphonic acid, p-toluenesulphonic acid, camphor sulphonic acid, methane sulphonic acid, guaiazulene sulphonic acid, maleic acid, fumaric acid, succinic acid, tartaric acid, lactic acid, citric acid, ascorbic acid, glycolic acid, salycilic acid, acetic acid, propionic acid, gluconic acid, benzoic acid, acetamino-acetic acid, hydroxy-ethane sulphonic acid.
The free bases can be produced from the salts of the .. . ...

- :.: - . ~

.

- lO~lS~O
compounds in the usual manner, for example, by treating a solution in an organic medium such as alcohols e.g. methanol with soda or with a solution of caustic soda.
Compounds having the formula I which contain asymmetric carbon atoms and usually are obtained as racemates can be split into the optically active isomers in a known manner, for example, by means of an optically active acid. However, it is also pos-sible to initially use an optically active starting substance and a corresponding optically active or diastereomeric form is then obtained as the final product.
The starting compounds used in the process can be pro-duced, for example, according to the process in Canadian Patent No. 990,289 or in a manner exactly analogous to this process.
Examples of the compounds according to the invention are compounds, wherein the radical Rl in the formula I represents an alkyl group containing 1 to 6 carbon atoms which R2 represents hydrogen, or compounds wherein Rl in the formula I represents an alkyl group containing 1 to 6 carbon atoms and R2 represents chlorine or fluorine, or compounds wherein Rl represents chlorine or fluorine.
The compounds according to the invention are suitable for the production of pharmaceutical compositions and preparations.
The pharmaceutical compositions or drugs contain, as the active substance, one or several compounds according to the invention, if required in mixture with other pharmacologically or pharma-ceutically active substances. The drugs can be produced with the ~ -use of conventional pharmaceutical auxiliaries and other con- ~-ventional fillers and diluents.
For example, substances which are recommended and/or listed in the following references form the literature as auxiliaries for pharmacy, cosmetics and related fields are .
.. , ~ ~ ' - ', ' '' ' suitable as this kind of fillers and auxiliaries: Ullmann's Encyklopàdie der technischen Chemie, Vol. 4 (1953), page 1 to 39;
Journal of Pharmaceutical Sciences, Vol. 52 (1963), page 918 ff, H.v. Czetsch-Lindenwald, Hilfsstoffe fur Pharmazie und angrenzende Gebiete; Pharm. Ind., No. 2, 1961, page 72 ff; Dr. H. P. Fiedler, Lexikon der Hilfsstoffe fùr Pharmazie, Kosmetik und angrenzende Gebiete, Cantor KG., Aulendorf i. Wurtt. 1971.
Examples are gelatin, natural sugar such as sucrose or lac:tose, lecithin, pectin, starch, for example, cornstarch, tylose, talc, lycopodium, silica for example, colloidal silica, cellulose, cellulose derivatives for example, cellulose ethers in which the cellulose-hydroxy groups are partially etherified with lower saturated aliphatic alcohols and/or lower saturated aliphatic oxy-alcohols, for example, methoxy-propyl cellulose stearates, magnesium and calcium salts of fatty acids, containing 12 to 22 carbon atoms, particularly of the saturated fatty acids for example, stearates, emulsifiers, oils and fats, particularly vegetable oils for example, peanut oil, castor oil, olive oil, sesame oil, cottonseed oil, corn oil, mono-, di-arid triglycerides of saturated fatty acids C12H2402 to C18H3602 and their mixtures, 20 pharmaceutically compatible monohydric or polyhydric alcohols and polyglycols such as polyethylene glycols as well as deriva-tives thereof, esters of aliphatic saturated or unsaturated fatty acids having from 2 to 22 carbon atoms, particularly 10 to 18 carbon atoms with monohydric aliphatic alcohols having 1 to 20 carbon atoms or polyhydric alcohols such as glycols, glycerine, diethylene glycol, pentaerythritol, sorbitol, and mannitol which, if required, can also be etherified, benzyl benzoate, dioxolanes, glycerin formals, glycol furoles, dimethyl acetamide, lactamides, lactates, ethyl carbonates and silicones particularly medium-vis-30 cosity dimethyl polysiloxanes and the like.
For example, water or physiologically compatible organicsolvents are suitable for the production of solutions, as for . . . . .. . . . . .

example, ethanol, l,2-propylene glycol, polyglycols and their derivatives, dimethyl sulphoxide, fat alcohols, triglycerides, partial esters of glycerin, and paraffins.
For the production of the preparation known and conventional dissolving intermediaries can be used, for example, polyoxyethylated fats, polyoxyethylated oleotriglycerides, linolized oleotriglycerides. Examples of oleotriglycerides are olive oil, peanut oil, castor oil, sesame oil, cottonseed oil, corn oil (see Dr. H. P. Fiedler "Lexikon der Hilfsstoffe fur Pharmazie, Kosmetik and angrenzende Gebiete" 1971, page 191 to 195). In this connection "polyoxyethylated" means that the substances concerned contain polyoxy-ethylene chains whose de-gree of polymerization usually is between 2 and 40 and part-icularly between 10 and 20. These polyoxyethylated substances can be obtained, for example, by reaction of the corresponding glycerides with ethylene oxide, for example, 40 moles of ethylene oxide per mole of glyceride.
The addition of preservatives, stabilizers, buffer substances, taste corrigents, antioxidants and complexing agents (for example, ethylene diamino tetraacetic acid) is also possible.
If required, the pH range may be adjusted for the stabilization of the active substance molecule to approximately 3 to 7 with physiologically compatible acids or buffers. In general, a pH
value as neutral as possible to weakly acid (to pH 5) is pre-ferred.
For example, sodium metabisulphite, ascorbic acid, gallic acid, gallic alkyl ester, butyl hydroxy anisole, nor-dihydro guaiaric acid, tocopherols as well as tocopherols +
synergists, substances which bind heavy metals by complexing action, for example, lecithin, ascorbic acid, phosphoric acid are used as antioxidants. The addition of the synergists substantially increases the antioxygenating action of the ~04~
tocopherols.
Thus, sorbic acid, p-hydroxy benzoic esters for example, lower alkyl ester, benzoic acid, sodium benzoate, trichloro isobutyl alcohol, phenol, cresol, benzethonium chloride and formalin derivatives are suitable as preservatives.
The pharmacological and galenic handling of the compounds accordin~ to the invention is carried out by means of the conventional standard methods. For example, active sub-stances(s) and auxiliaries and/or fillers are properly mixed by stirring or homogenizing (for example, by means of colloid mills, ball mills~ usually at temperatures between 20 and 80C, pre-ferably between 20 and 50C.
The drugs can be administered, for example, orally, parenterally, rectally, vaginally, perlingually or locally. The addition of other active medical substances is possible.
The compounds according to the invention show a good anti-convulsive and anxiety-preventing effect and/or a sedative effect, for example, in the Cardiazol shock test (mice), in the fighting test according to Tedeschi (mice) as well as in the motility test (mice) in the "ring" cage according to F. Heim.
This ~ffect is comparable to that of the known drug chloro diazepoxide. The lowest effective dose in the animal test ~, mentioned above is, for example.
0.5 mg per kg orally 0.2 mg per kg sublingually 0.1 mg per kg intravenously As a general dose range for obtaining an effect (animal test as above) the following dose is suitable, for example, 0.5 to 20 mg per kg orally 0.2 to 8 mg per kg sublingually 0.1 to 4 mg per kg intravenously ~-The compounds according to the invention are indicated .
- ::

. . .~ .

for states of anxiety, tension and restlessness, vegetative dystonia, irritability, nervousness, mood instability, stage fright, sensitivity to changes in weather, behavioral and adaptation disorders in children, functional cardiovascular, gastrointestinal and respiratory disorders, as well as for menstrual and climacteric disorders, prior to operations and in obstetrics.
The pharmaceutical preparations usually contain between 1 and 10% of the active component(s) according to the invention.
They can be dispense, for example, in the form of tablets, capsules, pills, dragées, suppositories, ointments, jellies, creams, powders, liquid, dusting powders or aerosols. For example, oily or aqueous solutions or suspensions or emulsions are suit-able as liquids. Tablets containing between 5 and 50 mg of the active substance or solutions containing between 0.1 and 1%
of the active substance are preferred forms of application.
The single dose of the active component relative to ~-the free base can be, for example, a) for oral drug forms between 1 and 50 mg b) for parenteral drug forms (for example, intravenously and intramuscularly) between 0.1 and 10 mg c) for drug forms to be inhaled (solutions or aerosols) between 0.2 and 20 mg d) for drug forms to be applied rectally or vaginally between 0.2 and 20 mg For example, three times daily from 1 to 3 tablets containing from 1 to 50 mg of active substance can be recommended or, for example, for intravenous injection 1 to 3 times daily 1 ampule containing 0.5 to 2 ml with 0.1 to 10 mg of substance.
When dispensed orally the minimum daily dose is, for example, 1.0 mg, and the maximum daily dose must not exceed 150 mg. The parenteral dose is between approximately 0.1 to 50 mg per kg of body weight.
For the treatment of cats and dogs the single oral dose usually is between approximately 1 and 50 mg per kg of body weight.
For the treatment of horses and cattle the single oral dose usually is between approximately 1 and 200 mg per kg of body weight and the single parenteral dose between approximate-ly 0.1 and 50 mg per kg.
In mice the acute toxicity of the compounds according to the invention (expressed by the Ld 50 mg/kg; method acco~ding to Miller and Tainter: Proc. Soc. Exper. Biol. a. Med. 57 (1944) 261) is, for example, for oral application between 200 and 2000 mg per kg (or above 2000 mg per kg).
The drugs can be used in human medicine, veterinary medicine and in agriculture either alone or in mixture with other pharmacologically active substances.
The present invention will be further illustrated by way of the following examples Example 1 1-methyl-4H-6-phenyl-8-chloro-s-triazolo-(4,3-a)-pyrido--(2,3-f)-1,4-diazepine /,N
A H3C - C ~ ~ ~ N

Cl ~ ~ ~ CH2 A mixture of 6 g of acetyl hydrazine, 10 g of 5-phenyl--6-azo-7-chloro-1,2-dihydro-3H-1,4 benzodiazepine-thione-(2) and 30 50 ml of dioxane is heated for 20 minutes to a temperature of 50 to 60C. The compound which crystallizes out upon cooling is - ' `

- : : ' ~

- 1()41S(J O
filtered with suction (and, if reguired, recrystallized from ethanol) and subsequently heated for 30 minutes in 40 ml of n-hexanol to a temperature of 140 to 150C. The substance crystallizes upon cooling and is recrystallised from hexanol.
m.p. = 258 to 260C, yield: 3.5 y The starting substance used is produced as follows:
A mixture of 54 ~ of 5-phenyl-6-aza-7-chloro-1,2-dihydro-3H-1,4-benzodiazepinone-(2), 44 g of phosphorus pentasulphide and 600 ml of toluene are boiled under nitrogen for 2.5 hours with reflux. The granular precipitate is filtered with suction, several times thoroughly stirred with chloroform, then treated with aqueous ammonia and once more extracted with chloroform.
The thione crystallizes in a pure form from the extracts upon drying. Yield: 30 g; m.p. = 202C

.

'4' 4lsdo ~ Supplem ntary Dlsclosure Example 2 l-methyl-4H-6-(o-chloro-phenyl)-8-chloro-s-triazolo-(4,3-a)-pyrido-(2,3-f)-1,4-diazepine N ~
H3C-C~ N
,D N--C ~
C1 1 N ~ C 3 N ~ 2 ~ Cl This compound is produced from 6 g of acetyl hydrazine ; and 11 g of 5-(o-chloro-phenyl)-6-aza-7-chloro-1,2-dihydro-3H-1,4-benzodiazepine-thione-(2) analogously to Example 1. Gross yield: 5 g. Yield upon recrystallization from hexanol: 2 g.
¦ Melting point: 262 to 264C.
~ Analytical Values ::
.
C: computed 55.8, obtained 55.3 to 55.5% ~ . .
~ H: computed 3.22, obtained 3.8%
; N: computed 20.34, obtained 20.3 to 20.4% ~ .:
Cl: computed 20.6, obtained 20.1% -The thione which is required as the starting material and has a melting point of 195 to 200C is obtained analogously to the thione used in Example 1. . :
Example 3 l-ethyl-4H-6-(o-chloro-phenyl)-8-chloro-s-triazolo-(4,3-a)-pyrido-(2,3-f)-1,4-diazepine N
C2H5-~ N~
~ N C
Cl ~ ~ N ~ :

~ Cl -- 11 -- : .

.. , ~ . - . .. : ~:
-- ... - , : ~ .. , . ... , . ,, . ~:

This compound is produced from 6 g of propionyl-hydrazine and 11 g of 5-(o-chloro-phenyl)-6-aza-7-chloro-1,2-dihydro-3H-l~4-benzodiazepine-thione-(2) analogously to Example 1, Gross yield: 6 g. Yield upon recrystallization from dimethy~
formamide/ether: 2.2 g Melting point 240 to 242C.
Example 4 l-methyl-4H-6-phenyl-8-chloro-s-triazolo-(4,3-a)-pyrido-(2,3-f)-1,4-diazepine N

H3C _ Cl \N

Cl ~7 ~ 6 S ; 2 .,~
~ .
6 g of acetyl hydrazine and 10 g of S-phenyl-6-aza-7-chloro-1,2-dihydro-3H-1,4-benzodiazepine-thione-(2) are heated on a ~ -water bath for 10 minutes to 100C while hydrogen sulphide is split off. The reaction mixture is then heated to a temperature of 220 to 240C until the melt thus formed solidifies a~ain (5 to 10 minutes). After cooling the fused cake it is dissolved in a small amount of dimethyl formamide and mixed with ether until I it is rendered turbid. The substance crystallizes upon seeding.
! Melting point: 258 to 260~C~ yield; 4 g.
Example S
l-methyl-4H-6-(o-chloro-phenyl)-8-chloro-s-triazolo-(4,3-a)-pyrido-(2,3-f)-(1,4)-diazepine ¦ (The same compound is also obtained according to Example 2).
A mixture of 2.625 g of 5-(o-chloro-phenyl)-6-aza-7-30 chloro-1,2-dihydro-3H-benzodiazepinon-(2)-imine, 2.6 g of acetyl hydrazine, 55.1 cu m of methanol and 0.47 cu m of formic acid is boiled for 2.5 hours with reflux while stirring. The by-- ~ - .

~0415()0 product precipitating during the reaction is filtered with suction while hot. The filtrate is cooled in an ice bath. The separated crystals are filtered with suction and washed with methanol. The filtrate is then concentrated to approximately 10 cu m while a second fraction crystallizes. This fraction is also washed with methanol. On crystallization from methanol the yield is 1 g. Melting point: 240 to 242C.
The compound can also he obtained in the following manner:
6 g of acetyl hydrazine and 10 g of 5-(o-chloro-phenyl)-6-aza-7-chloro-1,2-dihydro-3H-1,4-benzodiazepinone-(2) are first heated on a water bath to a temperature of 220 to 240C until the melt thus formed solidifies again. On cooling the fused cake it is dissolved in a small amount of dimethyl for~amide and mixed with ether until it is rendered turbid. The substance which crystallizes upon seeding is recrystallized from hexanol.
Melting point: 240 to 241C. Yield: 1.5 g.

-r :'' ' ' ' " '- ' ~ ' : , ' ' ' : ' .: ' ~ '. ' ' .

Claims (25)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. A process for producing a compound having the general formula I

(I) wherein R1 represents an alkyl group containing 1 to 6 carbon atoms and R2 represents hydrogen or a halogen atom, a tautomer thereof or a pharmaceutically acceptable salt thereof which comprises reacting a compound having the general formula II

(II) wherein R2 is as above and X represents oxygen, sulphur, imino a benzyl-imino group or in its tautomeric form may represent an alkylthio or alkoxy group containing 1 to 5 carbon atoms or an alkyl or dialkyl-amino group in which the alkyl radicals con-taining 1 to 6 carbon atoms, with a compound having the formula N2H - NH - COR1 (III) wherein R1 is as above, and simultaneously or subsequently cyclizing the product so formed to the compound having the formula I and, when the salt is required reacting the free to base with a suitable acid.

2. A process as claimed in claim 1 in which the reaction is effected at a temperature in the range 50 to 160°C.

3. A process as claimed in claim 2 in which the reaction is effected in a organic solvent.

4. A compound having the general formula (I) wherein R1 is an alkyl group containing 1 to 6 carbon atoms and R2 represents hydrogen or a halogen atom, a tautomer thereof or a pharmaceutically acceptable salt thereof when prepared by the process as claimed in claim 1, 2 or 3 or an obvious chemical equivalent thereof.

5. A process as claimed in claim 1 in which reactants R1 is an alkyl group having 1 to 6 carbon atoms and R2 is hydrogen, chlorine or fluorine.

6. A compound of formula I given in claim 1 or a tautomer or pharmaceutically acceptable salt thereof wherein R1 and R2 are as in claim 5 when prepared by the process as claimed in claim 5 or an obvious chemical equivalent thereof.

7. A process as claimed in claim 5 in which R1 is an alkyl group having 1 to 4 carbon atoms.

8. A compound of formula I given in claim 1 or a tautomer or pharmaceutically acceptable salt thereof wherein R1 is an alkyl group having 1 to 4 carbon atoms and R2 is hydrogen, chlorine or fluorine when prepared by the process as claimed in claim 7 or an obvious chemical equivalent thereof.

9. A process as claimed in claim 5 in which R1 is an alkyl group having 2 or 3 carbon atoms.

10. A compound of formula I given in claim 1 or a tautomer or pharmaceutically acceptable salt thereof wherein R1 is a alkyl group having 2 or 3 carbon atoms and R2 is hydro-gen, chlorine or fluorine when prepared by the process as claimed in claim 9 or an obvious chemical equivalent thereof.

11. A process as claimed in claim 9 in which in the reactants R2 is hydrogen.

12. A compound of formula I given in claim 1 or a tautomer or pharmaceutically acceptable salt thereof wherein R1 is a alkyl group having 2 or 3 carbon atoms and R2 is hydrogen when prepared by the process as claimed in claim 11 or an obvious chemical equivalent thereof.

13. A process as claimed in claim 1 in which in the reactants R1 is methyl and R2 is hydrogen.

14. A process as claimed in claim 1 which comprises heating a mixture of 5-phenyl-6-aza-7-chloro-1,2-dihydro-3H-1,4-benzodiazepine-thione-(2) in dioxane with acetyl hydrazine.

15. The compound 1-methyl-4H-6-phenyl-8-chloro-s-triazolo-(4,3-a)-pyrido-(2,3-f)-1,4-diazepine when prepared by the process as claimed in claim 13 or 14 or an obvious chemical equivalent thereof.

CLAIMS SUPPORTED BY THE SUPPLEMENTARY
DISCLOSURE

16. A process as claimed in claim 1 in which the reactants R1 is methyl, and R2 is chlorine in the ortho position.

17. A process as claimed in claim 1 which comprises heating a mixture of 5-(o-chloro-phenyl)-6-aza-7-chloro-1,2-dihydro-3H-1,4-benzodiazepine-thione-(2) in dioxane with acetyl hydrazine.

18. A process as claimed in claim 1 which comprises refluxing 5-(o-chloro-phenyl)-6-aza-7-chloro-1,2-dihydro-3H-benzodiazepinon-(2)-imine in methanol and in the presence of formic acid with acetyl hydrazine.

19. A process as claimed in claim 1 which comprises heating 5-(o-chlorophenyl)-6-aza-7-chloro-1,2-dihydro-3H,1,4-benzodiazepinone-(2) at a temperature of from 220 - 240°C with methyl hydrazine until the melt formed solidifies and dissolving the product obtained in dimethyl formamide and mixing the solution with ether until turbid.

20. 1-methyl-4H-6-(o-chloro-phenyl)-8-chloro-s-triazolo-(4,3-a)-pyrido-(2,3-f)-1,4-diazepine whenever prepared or produced by the process as claimed in claim 16, 17 or 18 or an obvious chemical equivalent thereof.

21. A process as claimed in claim 1 in which the reactants R1 is ethyl and R2 is chlorine in the o-position.

22. A process as claimed in claim 1 which comprises heating 5-(o-chloro-phenyl)-6-aza-7-chloro-1,2-dihydro-3H-1,4-benzodiazepine-thione-(2) in dioxane with propionyl hydrazine.

23. 1-ethyl-4H-6-(o-chloro-phenyl)-8-chloro-s-triazolo-(4,3-a)-pyrido-(2,3-f)-1,4-diazepine whenever prepared or produced by the process as claimed in claim 21 or 22 or an obvious chemical equivalent thereof.

24. A process as claimed in claim 1 which comprises heating acetyl hydrazine with 5-phenyl-6-aza-7-chloro-1,2-dihydro-3H-1,4-benzodiazepine-thione-(2) at 100°C to split off hydrogen sulphide and heating the reaction mixture to 220°C
to 240°C until the melt formed solidifies.

25. 1-methyl-4H-6-phenyl-8-chloro-s-triazolo-(4,3-a)-pyrido-(2,3-f)-1,4-diazepine whenever prepared or produced by the process as claimed in claim 24 or an obvious chemical equivalent thereof.