DE1965894C2 - 2-hydrazino-5-phenyl-3H-1,4-benzodiazepine derivatives and process for their preparation - Google Patents

Description

worked up, with 2-hydrazino-5-phenyI-7-trifluoromethylr3H-1,4-benzodiazepine as a crystalline powder from melting point 127 ° C (sintering) or 133 to 135 ° C (with foaming) is obtained.

Elemental analysis: Calculated for Ci ^ Hi ₃ F ₃ N ₄ : C6037 H4.12 N 17.60 Found: C60.06H3.96N17.40

This shape is also suitable for this procedure.

The compound of formula (III) can, for example be prepared according to the procedure outlined in Journal of Organic Chemistry «29, 231 (1964)

The alkyl radical R ₅ is preferably an alkyl radical having 1 to 6 carbon atoms, e.g. For example, a methyl radical, ethyl radical, propyl radical, Isopropyirest, butyl, sec-butyl, tert-butyl, aryl or hexyl radical is The aralkyl group for R ₅ is z. B a benzyl or phenylethyl radical

The reaction is generally carried out in the presence of a solvent (e.g. methanol, ethanol and aqueous mixtures of methanol and ethanol) at about room temperature or optionally with heating to the boiling point of the solvent used. The hydrazine is used in an amount of about 1 to 10 moles per mole of the compound (III) are used

The 2-hydrazino-'5-phenyl-3H-l, 4-benzodiazepine derivatives (I) prepared in this way can by customary methods, for example by evaporation of the Solvent from the reaction mixture, are isolated.

The new compounds of the formula (I) are valuable intermediates for the preparation of the new S-TriazoIo [4,3-aIl, 4] -bfc; izodiazepine according to Master patent 19 55 349, which have muscular aping, calming and dampening effects and therefore are valuable as muscle relaxants, anticonvulsants, sedatives, tranquilizers.

example 1

To a suspension of 3.4 parts of 2-amino-7-chloro-S-phenyl-SH-l. ^ - benzodiazepine dihydrochloride in 60 Parts by volume of methanol are given 1.25 parts of 80% hydrazine hydrate. The suspension turns 40 Stirred minutes, diluted with water and extracted with methylene chloride. The extract is washed with Washed with water and dried over anhydrous sodium sulfate, whereupon the solvent was evaporated will. The residue is recrystallized from a mixture of methylene chloride and benzene, whereby 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine is obtained in the form of colorless prisms. Melting point about 170 ° C (browning); 202 to 204 ° C (dec.)

Elemental Analysis: Calculated WrC ₁₅ HuCIN ₄ : C 63.27 H 4.60 N 19.68 Found: C 63.43 H 4.48 N 19.27

Example 2

To a mixture of 9.1 parts of 2-amino-5-phenyl-7-trifluoromethyl-3H-1,4-benzodiazepine, 150 parts by volume Ethanol and 3.6 parts by volume of glacial acetic acid are given 4.5 parts by volume of 100% hydrazine hydrate. That The mixture is stirred for 30 minutes at room temperature and in the manner described in Example 1

Example 3

. To a mixture of 5.6 parts of 2-amino-7-nitro-5-phenyI-3H-1,4-benzodiazepine, 200 parts by volume of ethanol and 2.4 parts by volume of glacial acetic acid, 5 parts by volume of 80% hydrazine hydrate are added with stirring. That The mixture is stirred for 30 minutes at room temperature and in the manner described in Example 1 worked up, with 2-hydrazino-7-nitro-5-pheny -! - 3H- 1,4-benzodiazepine as a reddish, viscous oily substance is obtained.

Example 4 To a solution of 1fr parts of 2-amino-7-chloro-3-

isobutyl-5-phenyl-3H-1,4-benzodiazepine and 25 parts 100% hydrazine hydrate in 400 parts by volume of methanol 6 parts of glacial acetic acid are added while stirring and

is cooled with ice. The * mixture will then be 5 hours stirred at room temperature. After adding water the reaction mixture is extracted with chloroform

The chloroform layer is washed with water and

dried over sodium sulfate. The solvent is evaporated by treating the residue with

Isopropyl ether becomes 7-chloro-2-hydrazino-3-isobutyl-5-

phenyl-3H-1,4-benzodiazepine in the form of colorless

Crystals with a melting point of 165 to 168 ° C were obtained. This product is the same as in Example 7

manufactured product identical.

Example 5

To a solution of 2 parts of 7-chloro-2-methyImercapto-5-phenyI-3H-1,4-benzodiazepine in 70 parts by volume Ethanol is given to 5 parts by volume of 80% hydrazine hydrate. The mixture is left for 3 days at room temperature left the door. After evaporation of the solution by means of a small amount of water is added to the residue, 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine being obtained in the form of crystals. By recrystallization from a mixture of Methylene chloride and benzene are obtained crystals of melting point 175 ° C (browning) and 205-207 ⁰ C (dec.). This product is identical to the product produced according to Example 1.

Example 6

To a solution of 2.9 parts of 7-chloro-13-dihydro-5-phenyI-2H-1,4-benzodiazepine-2-thione in a mixture of 2.5 space hard dimethyl sulfoxide and 100 Parts of the volume of ethanol are 5 parts of the volume of 80% Given hydrazine hydrate. The mixture will last 24 hours ditched. After evaporation of the solvent under reduced pressure, the residue becomes with Diluted water, followed by extraction with methylene chloride. The methylene chloride layer is over Dried sodium sulfate and evaporated the solvent. By treating the residue with benzene 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiaze-din is obtained. Recrystallization from a mixture

of methylene chloride and benzene gives crystals with a melting point of 205 to 207 ⁰ G (decomp.). This product is identical to the product produced according to Examples 1 and 5

Example, 7

; To a solution of 1.6 parts of 7-chloro-3-isobutyl-2-methylmercapto-5-phenyl-3H-1,4-benzodiazepine 40 parts of lOOVoiges are in 150 parts of methanol Given hydrazine hydrate. The mixture is refluxed for 4.5 to hours and poured into water, followed by extraction with chloroform. The chloroform layer is washed with water and dried over sodium sulfate whereupon the solvent is evaporated. Treatment of the residue with diethyl ether gives 7-chloro-2-hydrazino-3-isobutyl-5-phenyl-3H-1,4-benzodiazepine obtained in forra of crystals. By recrystallization from a mixture yoE chloroform and η-hexane, colorless crystals with a melting point of 168 to 169 ° C. are obtained.

Elemental analysis:
Calculated for Ci ₉ H ₂ ICIN ₄ :
C 66.95 H 621
Found:
C 6721 H 6.19

N 16.44
N 16.70
Example 8

20th

25th

To a suspension of 143 parts of 2-amino-7-chloro-S-phenyl-SH-t / t-benzodiazepine ^ N-oxide in 400 parts by volume of methanol, 12.5 parts by volume are 100% Hydrazine hydrate and 10 parts by volume of methanol, which is saturated with hydrogen chloride, are given. The mixture is refluxed for 10 minutes and the resulting solution to half of the original Confined in volume. The concentrate is poured into 500 parts by volume of water and the resulting oily Substance extracted with chloroform. The chloroform slips is dried over sodium sulfate and evaporated. By treating the residue with Diethyl ether becomes 7-chloro-2-hydrazino-5-phenyl-3H-: 1,4-benzodiazepine-4N-oxide as pale yellow powdery form Crystals with a melting point of 262-263 ° C were obtained.

Elemental analysis:
Calculated for Ci ₅ HnClN ₄ O:
C 59.90 H 436 N 18.63
Found:
C 60.05 H 4.13 N 18.41

Example 9

To a mixture of 3 parts of 2-amino-7-nitro-5-phenyI-3H-1,4-benzodiazepine-4N-oxide and 100 parts by volume of ethanol become 2 parts of 100% hydrazine hydrate and 1.8 parts by volume of acetic acid. The mixture becomes light on the water bath for some time heated, with a solution int, and about 20 Minutes at room temperature geiübru The precipitated Crystals are separated off and washed with ethanol and then with diethyl ether, 2-hydrazino-7-nitro-5-phenyl-3H-1,4-benzodiazepine-4N-oxide in the form of yellow needles with a melting point of 176 ° C (sintering) and 226 ° C (dec.).

Elemental analysis:
Calculated for Ci ₅ H ₁₃ N ₅ O ₃ :
C 57.87 H 421 N 22.50
Found:
C 5738 H 4.01 N 22.26

Claims (2)

NHNH-, (D R ₄ wherein R _{2 is} a hydrogen atom or an alkyl radical having 1-4 carbon atoms, R _{3 is} a halogen atom or a trifluoromethyl group or nitro group and R _{4 is} a hydrogen atom or a halogen atom, their N ₄ -OxIdC and the acid salts of these compounds. 2. Process for the preparation of compounds according to claim 1, characterized in that one in a manner known per se