CH637654A5 - Triazolobenzazepine derivatives, process for their preparation and pharmaceutical preparations containing them - Google Patents

Abstract

The novel triazolobenzazepine derivatives correspond to the formula: <IMAGE> in which A, R<1>, R<2>, X and Z have the meanings given in Patent Claim 1. The compounds of the formula I have outstanding pharmacological actions and are utilisable as medicaments, such as muscle relaxants, analgesics and anti-inflammatory agents. Also described, then, are pharmaceutical preparations which contain the compounds I as active compound, and processes for the preparation of the latter.

Description

       

  
 

** WARNING ** beginning of DESC field could overlap end of CLMS **.

 
EMI2.1
 in which R1 and R2 are hydrogen or alkyl radicals, X for
EMI2.2
 wherein R3 and R4 are hydrogen, alkyl radicals, aryl radicals or aralkyl radicals and R5 is hydrogen or an alkyl radical, and R7 is an alkyl radical or aralkyl radical and ring A is unsubstituted or mono- or polysubstituted by halogen atoms, lower alkyl radicals, lower alkoxy radicals and / or trifluoromethyl radicals is characterized in that compounds of the formula:
EMI2.3
 in which Y is a halogen atom or a group of the formula -S (O) nR5, in which R6 is an alkyl radical or aralkyl radical and n is 1 or 2, and the other symbols have the meanings given above, with an alcoholate of the formula:

  :
R7-OM, (VI) in which M is an alkali metal and R? has the meaning given above.



   7. Process for the preparation of compounds of the formula:
EMI2.4
 in which Rl, R2 and R6 have the meanings given in claim 3 and the ring is unsubstituted or substituted in the manner mentioned in claim 3, characterized in that compounds of the formula Ia in which R3 and R4 are hydrogen, using a Oxidizing agent oxidized.



   8. Process for the preparation of compounds of the formula:
EMI2.5
 in which R1, R2 and R6 have the meanings given in Claim 3, R5 represents hydrogen or alkyl and ring A is unsubstituted or substituted in the manner mentioned in Claim 3, characterized in that compounds of the formula Ia in which R3 and R4 are hydrogen, with an aldehyde of the formula RtCHO, in which R5 has the meaning given above.



   The invention relates to new, valuable triazolbenzazepine derivatives.



   From U.S. Patent No. 4,002,638 to Y. Kuwada et al are benzazepine derivatives of the formula:
EMI2.6
 wherein the ring A is unsubstituted or substituted by halogen, nitro, alkyl, alkoxy or trifluoromethyl, R is hydrogen or optionally substituted alkyl, X is oxygen or sulfur and Y is -CHfCH2- or CH = CH-, and their pharmaceutically acceptable salts known. These compounds have pharmacological effects such as analgesic and muscle relaxant effects.



   New triazolbenzazepine derivatives of the formula:
EMI2.7
 in which R1 and R2 are hydrogen or alkyl, X for
EMI 2.8
 wherein R3 and R4 are hydrogen, alkyl, aryl or aralkyl and R5 is hydrogen or alkyl, Z is -SR6, -S (O) "R6 or -OR7, wherein R6 and R7 are alkyl or aralkyl and n is 1 or 2 , is and the ring A is unsubstituted or mono- or polysubstituted with halogen, lower alkyl, lower alkoxy or trifluoromethyl, and their salts, which are effective and valuable as medicaments, for example as muscle relaxants, analgesics and anti-inflammatory agents.



   The invention thus relates to the new verb



  (I) and their salts, which have excellent pharmacological activities. The invention is also directed to pharmaceutical preparations which contain the compounds (I) and to the processes for preparing the compounds (I) as defined in claims 3 to 8.



   In the above formula (I), the alkyl radicals denoted by R1, R2, R3, R4, R5, R6 and R7 can, for example, lower alkyl radicals having preferably about 1 to 4 carbon atoms (for example methyl, ethyl, propyl, isopropyl, butyl, isobutyl , sec. butyl, t-butyl, cyclopropylmethyl). The aralkyl radicals R3, R4, R6 and R7 can be aliphatic radicals having about 1 to 4 carbon atoms which are substituted by a phenyl radical (ie phenyl-C1-C4-alkyl), for example benzyl, phenethyl, z-phenylethyl and phenylpropyl, and the aryl radicals denoted by R3 and R4 can be, for example, phenyl radicals. These aralkyl and aryl radicals can each have any number of substituents in the substitutable positions on the benzene ring, substituents of the same type as on ring A, which are mentioned below, being suitable.

  The above-mentioned radicals R1 and R2 and R3 and R4 can be the same or different.



   If the ring A is mono- or polysubstituted, it can contain the following substituents: halogen atoms (e.g. fluorine, chlorine, bromine or iodine), lower alkyl radicals preferably with about 1 to 4 carbon atoms (e.g. methyl, ethyl, propyl, isopropyl and Butyl), lower alkoxy radicals, preferably having about 1 to 4 carbon atoms (for example methoxy, ethoxy, propoxy, isopropoxy and butoxy) and trifluoromethyl. These substituents are located on substitutable positions of ring A and can be the same or different.



  The maximum number of substituents can be up to 4.



   Examples of compounds (I) according to the invention are: 3-methylthio-11H-s-trizolo [3,4-b] [3] benzazapine 3-ethylthio-11H-s-trazolo [3,4-b] [ 3] benzazepine 3-n-propylthio-11H-s-trizolo- [3,4-b] [3] benzazepine 3-isopropylthio-11H-s-triazolo [3,4-b] [3] benzazepine 3-n- Butylthio-11 Hs-triazolo [3, 4-b] [3] benzazepine
11-methyl-3-methylthio-11H-s-triazolo [3,4-b] [3] benzazepine 3-ethylthio-11-methyl-11H-triazolo [3,4-b] [3] benzazepine 3-isopropylthio- 1 1-methyl-1 1H-trazolo [3,4-b] [3] benzazepine
11-ethyl-3-methylthio-11H-s-triazolo [3,4-b] [3] benzazepine
11-ethyl-3-ethylthio-11H-s-triazolo [3,4-b] [3] benzazepine
11-ethyl-3-isopropylthio-1 1H-s-triazolo [3,4-b] [3] benzazepine
11-isopropyl-3-methylthio-11H-s-triazolo [3,4-b] benz azepine ethylthio-11-isopropyl-11H-s-triazolo [3,4-b] [3] benzazepine
11-butyl-3-methylthio-1

   1H-s-triazolo [3,4-b] [3] benzazepine-11,11-dimethyl-3-methylthio-11 Hs-triazolo [3,4-b] [3] benzazepine 11,11-dimethyl-3 -ethylthio- 11H-s-triazolo- [3,4-b] [3] benz azepine 11 -ethyl-1 l-methyl-3-methylthio-l 1H-s-triazolo [3, Pb] [3] benzazepine 11 -Benzyl-3-methylthio- 11 Hs-triazolo [3,4-b] [3] benzazepine 3-methylthio-1-phenyl-11 1H-s-triazolo [3,4-b] [3] benzazepine 3-ethylthio -11 -phenyl-1 1 Hs-triazolo [3,4-b] [3] benzazepine 6-methyl-3-methylthio-1 1 Hs-triazolo [3,4-b] [3 benzazepine 6-ethyl-3- methylthio-11H-s-triazolo [3,4-b] [3] benzazepine 5-methyl-3-methylthio-11H-s-triazolo [3,4-b] [3] benzazepine 5-ethyl-3-methylthio- 11 Hs-triazolo [3,4-b] [3] benzazepine 5-isopropyl-3-methylthio-11 Hs-triazolo

   [3, 4-b] [3] benzazepine 5,11 -dimethyl-3-methylthio-11 H-s-triazolo [3,4-b] [3] benz azepine
3-methylthio-5,11,11-trimethyl-11H-s-triazolo [3,4-b] [3] benzazepine
5-methyl-3-methylthio-1 1-phenyl-1 1H-s-triazolo [3,4-b] [3] benzazepine
8-chloro-3-methylthio-11H-s-triazolo [3,4-b] benzazepine
9-chloro-3-methylthio-1 1H-s-triazolo [3, 4-b] [3] benzazepine
10-chloro-3-methylthio-1 lH-s-triazolo [3,4-b] [3] benzazepine
8-bromo-3-methylthio-1 lH-s-triazolo [3, 4b] [3] benzazepine
8-methyl-3-methylthio-1 lH-s-triazolo [3,4-b] [3] benzazepine 8-methoxy-3-methylthio-11H-s-triazolo [3,4-b] [3] benzazepine 9 -Methoxy-3-methylthio-1 1 Hs-triazolo [3,4-b] [3] benzazepine
8,9-Dimethoxy-3-methylthio-1 1H-s-triazolo [3,4-b] [3] - benzazepine 3-methylthio-8-trifluoromethyl-1 <RTI

    ID = 3.16> 1H-s-triazolo [3,4-b] [3] benzazepine
11 -Methylene-3-methylthio-1 1H-s-triazolo [3,4-b] [3] benzazepine
11-ethylidene-3-methylthio-11H-s-triazolo [3,4-b] [3] benz azepine
3-methylthio-1 1-propylidene-1 1H-s-triazolo [3,4-b] [3] -benz azepine
8-chloro-11-methylene-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine
11-methylene-8-methyl-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine
11-methylene-8-methoxy-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine
11-methylene-9-methoxy-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine) 8,9-dimethoxy-11-methylene-3-methylthio-11H-s-rtiazole [3 , 4-b] [3] benzazepine
3-methylthio-11H-s-triazole [3,4-b] benzazepin-11-one 3-ethylthio-1 1H-s-triazole [3,4-b] [3] benzazepine-11-one
3-isopropylthio-11 H-s-triazole [3,4-b] [3] benzazepin- 1 1-one <RTI

    ID = 3.20> 8-chloro-3-methylthio-11 H-s-triazole [3,4-b] [3] benzazepin -11-one
8-methyl-3-methylthio-11H-s-triazole [3,4] [3] benzazepin -11-one
8-methoxy-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepin -11-one
9-methoxy-3-methylthio-1 1H-s-triazole [3,4-b] [3] benzazepin-11-one
3-methylthio-8-trifluoromethyl-1 1H-s-triazolo [3,4-b] [3] - benzazepin-1 1-one
3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzapepine
3-methylsulfonyl-11 H-s-triazole [3,4-b] [3] benzazepine
3-ethylsulfinyl-11 H-s-triazole [3,4-b] [3] benzazepine
3-ethylsulfonyl-11 H-s-triazole [3,4-b] [3] benzazepine
3-propylsulfinyl-11H-s-triazole [3,4-b] [3] benzapepine
3-propylsulfonyl-11 H-s-triazole [3,4-b] [3]

   benzazepine
3-isopropylsulfinyl-11H-s-triazole [3,4-b] [3] benzapepine
3-isopropylsulfonyl-11 H-s-triazole [3, 4-b] [3] benzapepine
3-butylsulfinyl-11H-s-triazole [3,4-b] [3] benzapepine
3-butylsulfonyl-11H-s-triazole [3,4-b] [3] benzapepine 1 1-methyl-3-methylsulfinyl-11 H-s-triazolo [3, 4-b] [3] benz azepine
11-methyl-3-methylsufonyl-11H-s-triazole [3,4-b] [3] benz azepine 3-ethylsulfinyl-11-methyl-11H-s-triazolo [3,4-b] [3] benz azepine
3-ethylsulfonyl-11-methyl-11H-s-triazolo [3,4-b] [3] benz azepine 3-isopropylsulfonyl-1 1-methyl-1 lH-s-triazolo [3,4-b] [3] - benzazepine
11-ethyl-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine
11-ethyl-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine
11-ethyl-3-ethylsulfinyl-11 H-s-triazole [3, 4-b] [3] benzazepine 11-ethyl-3-ethylsulfonyl-11 H-s-triazole [3, 4-b] [3] benzazepine

   3-methylsulfinyl-11-propyl-11H-s-triazole [3,4-a] [3] benz azepine 3-methylsulfonyl-l 1-propyl-1 1H-s-triazole [3,4-b] [3] benz azepine 11-isopropyl-3-methylsulfinyl-11H-s-triazole [3,4-a] [3] benz azepine 11-isopropyl-3-methylsulfonyl-11 Hs-triazole [3, 4-b] [3] benz azepine 11.1 1-dimethyl-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine 11,11 -dimethyl-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine 11,11 -dimethyl-3-ethylsulfinyl-11H-s-triazole [3,4-b] [3] benz azepine
11,11-dimethyl-3-ethylsulfonyl-11H-s-triazole [3,4-b] [3] benz azepine
11-ethyl-11-methyl-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine
11-ethyl-11-methyl-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine
11-benzyl-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benz azepine
11-benzyl-3-methylsulfonyl-11H-s-triazole [3,4-b]

   [3] benz azepine
3-methylsulfinyl-11-phenyl-11H-s-triazole [3,4-b] [3] benz azepine
3-methylsulfonyl-11-phenyl-11 Hs-triazole [3, 4-b] [3] benz azepine 3-ethylsulfinyl-11 -phenyl-1 1H-s-triazole [3,4-b] [3] benz azepine 3-ethylsulfonyl-11-phenyl-11H-s-triazole [3,4-b] [3] benz azepine 6-methyl-3-methylsulfinyl-1 1H-s-triazole [3,4-b] [3] benz azepine 6-methyl-3-methylsulfonyl-11 Hs-triazole [3,4-b] [3] benz azepine
5-methyl-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benz azepine
5-methyl-3-methylsulfonyl-1 lH-s-triazole [3,4-b] [3] benz azepine 5-ethyl-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benz azepine
5-ethyl-3-methylsulfonyl-11 Hs-triazole [3, 4-b] [3] benz azepine 5,11 -Dimethyl-3-methylsulfinyl-11 Hs-triazole [3,4-b] [3] benz- azepine
5,11-dimethyl-3-methylsulfonyl-11H-s-triazole [3,4-b] [3]

   benzazepine
3-methylsulfinyl-5, 11,11-trimethyl-11H-s-triazole [3,4-b] [3] benzazepine
3-methylsulfonyl-5.1 1.1 l-trimethyl-1 1H-s-triazole] 3,4-b [[3] benzazepine
5-methyl-3-methylsulfinyl-11-phenyl-11H-s-triazole [3,4-b] [3] benzazepine
5-methyl-3-methylsulfonyl-11-phenyl-11H-s-triazole [3,4-b] [3] benzazepine
8-chloro-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine
8-chloro-3-methylsulfonyl-11 H-s-triazole [3,4-b] [31 benzazepine
9-chloro-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine 9-chloro-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine
10-chloro-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine
10-chloro-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine
8-bromo-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine
8-bromo-3-methylsulfonyl-11 H-s-triazole [3,4-b] [3] benzazepine
8-methyl-3-methylsulfinyl-11 H-s-triazole [3,4-b] [3]

   benzazepine
8-methyl-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine 8-methoxy-3-methylsulfinyl-1 1H-s-triazole [3, 4-b] [3] benz azepine 8-methoxy-3-methylsulfonyl-11 Hs-triazole [3,4-b] [3] benz azepine 9-methoxy-3-methylsulfinyl-1 lH-s-triazole [3,4b] [3] benz-azepine 9 -Methoxy-3-methylsulfonyl-1 1H-s-triazole [3,4-b] [3] benz azepine 8,9-dimethoxy-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine 8,9-dimethoxy-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine 3-methylsulfinyl-8-trifluoromethyl-1 1H-s-triazole [3,4-b] [3 ] benzazepine 3-methylsulfonyl-8-trifluoromethyl-11H-s-triazole [3,4-b] [3] benzazepine 11-methylene-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benz azepine 11-methylene-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benz azepine

   3-ethylsulfinyl-11-methylene-11H-s-triazole [3,4-b] [3] benz azepine 3-ethylsulfonyl-11-methylene-1 1H-s-triazole [3,4-b] [3] benz azepine 11-ethylidene-3-methylsulfinyl-11H-s-triazole- [3,4-b] [3] benz azepine 11-ethylidene-3-methylsulfonyl-1 1H-s-triazole [3, 4-b] [3 ] benz azepine 3-methylsulfinyl-11-propylidene-11H-s-triazole [3,4-b] [3] benz-azepine 3-methylsulfonyl-11-propylidene-11H-s-triazole [3,4-b] [3,4-b] [ 3] benzazepine 8-chloro-11-methylene-3-methylsulfinyl-11 Hs-triazole [3,4-b] [3] benzazepine 8-chloro-11-methylene-3-methylsulfonyl-11H-s-triazole r3, 4 -b] - [3] benzazepine 11-methylene-8-methyl-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine 11-methylene-8-methyl-3-methylsulfonyl-11H- s-triazole [3,4-b] [3] benzazepine 11-methylene-8-methoxy-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine 11

     -Methylene-8-methoxy-3-methylsulfonyl- 1 lH-s-triazole- [3,4-b] [3] benzazepine 11-methylene-9-methoxy-3-methylsulfinyl-1 lH-s-triazole- [3 , 4-b] [3] benzazepine 11 -methylene-9-methoxy-3-methylsulfinyl-11 Hs-triazole [3,4-bl [3] benzazepine 8,9-dimethoxy-11-methylene-3-methylsulfinyl-11H -s-triazole [3,4-b] [3] benzazepine 8,9-dimethoxy-11-methylene-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine 3-methylsulfinyl-11H -s-triazol [3,4-b] [3] benzazepin-11-one 3-methylsulfonyl-11 Hs-triazol [3, 4-b] [3] benzazepin-1 1-one 3-ethylsulfinyl-11H-s -triazol [3,4-b] [3] benzazepin-11-one 3-ethylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepin-11-one 3-isopropylsulfinyl-11 Hs-triazole [ 3,4-b] [3] benzazepin-1 1-one 3-isopropylsulfonyl-

   11 Hs-triazole [3,4-b] [3] benzazepine-11-one 8-chloro-3-methylsulfinyl-l 11 Hs-triazole [3,4-b] [3] benzazepine -11-one 8- Chloro-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepin -11-one 8-methyl-3-methylsulfinyl-11 Hs-triazole [3,4-b] [3] benz- azepin-1 1-one 8-methyl-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benz azepin-1 1-one 8-methoxy-3-methylsulfinyl-l 1 Hs-triazole [ 3,4-b] [3] benz azepin-1 1-one
8-methoxy-3-methylsulfonyl-1 1H-s-triazole [3,4-b] [3jbenz-azepin-1 1-one
9-methoxy-3-methylsulfinyl-1 1H-s-triazole [3,4-b] [3] benz azepin-1 1-one
9-methoxy-3-methylsulfonyl-11 H-s-triazole [3,4-b] [3] benz azepin-11-one
3-methylsulfinyl-8-trifluoromethyl-11H-s-triazole [3,4-b] [3] benzazepin-1

   1-on
3-methylsulfonyl-8-trifluoromethyl-11 H-s-triazole [3,4-b] [3] benzazepin-1 1-one
3-benzylsulfinyl-1 1H-s-triazole [3,4-b] [3] benzazepine
3-benzylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine
3-methoxy-11 H-s-triazole [3,4-b] [3] benzazepine 3-ethoxy-11 H-s-triazole [3,4-b] [3] benzazepine
3-propoxy-11H-s-triazole [3,4-b] [3] benzazepine
3-isopropoxy-11 H-s-triazole [3,4-bj [3rd

   ] benzazepine
3-butoxy-11H-s-triazole [3,4-b] [3] benzazepine
3-benzyloxy-11H-s-triazole [3,4-b] [3] benzazepine
3-phenethyloxy-11H-s-triazole [3,4-b] [3] benzazepine
3-methoxy-11-methyl-11H-s-triazole [3,4-b] [3] benzazepine
3-ethoxy-11-methyl-11H-s-triazole [3,4-b] [3] benzazepine
11-methyl-3-isopropoxy-11H-s-triazole [3,4-b] [3] benzazepine
11-ethyl-3-methoxy-11H-s-triazole [3,4-b] [3] benzazepine
3-ethoxy-11-ethyl-11H-s-triazole [3,4-b] [3] benzazepine
3-methoxy-11-propyl-11H-s-triazole [3,4-b] [3] benzazepine
3-ethoxy-11-propyl-11H-s-triazole [3,4-b] [3] benzazepine
11-butyl-3-methoxy-11H-s-triazole [3,4-b] [3] benzazepine
11,11-dimethyl-3-methoxy-11H-s-triazole [3,4-b] [3] benz azepine
11,11-dimethyl-3-ethoxy-11 H-s-triazole [3,4-b] [3] benzazepine
11-ethyl-3-methoxy-11-methyl-11H-s-triazole [3,4-b] [3] benz

   azepine
11-benzyl-3-methoxy-11H-s-triazole [3,4-b] [3] benzazepine
11-benzyl-3-ethoxy-11H-s-triazole [3,4-b] [3] benzazepine
1-methoxy-11-phenyl-11H-s-triazole [3,4-b] [3] benzazepine 3-ethoxy-11-phenyl-11H-s-triazole [3,4-b] [3] benzazepine 3- Methoxy-6-methyl-11 Hs-triazole [3,4-b] [3] benzazepine 3-ethoxy-6-methyl-1 1 Hs-triazole [3,4-b] [3] benzazepine 3-ethoxy-6 -ethyl-1 1 Hs-triazole [3,4-b] [3] benzazepine 3-methoxy-5-methyl-11H-s-triazole [3,4-b] [3] benzazepine 3-ethoxy-5-methyl -11H-s-triazole [3,4-b] [3] benzazepine 5-ethyl-3-methoxy-11 Hs-triazole [3,4-b [3] benzazepine 3-ethoxy-5-ethyl-11 Hs- triazole [3 4-b] [3] benzazepine 5,11-dimethyl-3-ethoxy-11H-s-triazole [3,4-b] [3] benzazepine 3-ethoxy-5-methyl-11-phenyl-11H -s-triazole [3,4-b] [3] benz azepine

   8-chloro-3-methoxy-11 Hs-triazole [3,4-b] [3] benzazepine 8-chloro-3-ethoxy-11 Hs-triazole 13,4-b] [3] benzazepine 9-chloro-3 -ethoxy- 11 Hs-triazole [3,4-b] [3] benzazepine
10-chloro-3-ethoxy-11H-s-triazole [3,4-b] [3] benzazepine 8-bromo-3-ethoxy-11H-s-triazole [3,4-b] [3] benzazepine 3- Methoxy-8-methyl-11H-s-triazole [3,4-b] [3] benzazepine 3-ethoxy-8-methyl-11H-s-triazole [3,4-b] [3] benzazepine 3,8- Dimethoxy-11H-s-triazole [3,4-b] [3] benzazepine 3-ethoxy-8-methoxy-11H-s1-triazole [3,4-b] [3] benzazepine 3,9-dimethoxy-1 1 Hs-triazole [3, 4-b] [3] benzazepine 3-ethoxy-9-methoxy-11H-s-triazole [3,4-b] [3] benzazepine 8,9-dimethoxy-3-ethoxy-11H- s-triazole [3,4-b] [3] benzazepine 3-ethoxy-8-trifluoromethyl-11H-s-triazole [3,4-b] [3] benzazepine 3-methoxy-11-methylene-11H-s- triazole [3,4-b] [3] benzazepine 3-ethoxy-l <RTI

    ID = 5. 18> l-methylene-1 1H-s-triazole [3,4-b] [3] benzazepine 1 I-ethylidene-3-methoxy-11H-s-triazole [3,4-b] [3] benzazepine 3- Methoxy-11-propylidene-11H-s-triazole [3,4-b] [3] benzazepine 8-chloro-3-methoxy-11-methylene-11H-s-triazole [3,4-b] [3] benzazepine 8-chloro-11-ethylidene-3-methoxy-11H-s-triazole [3,4-b] [3] benz azepine 3-methoxy-8-methyl-11-methylene-11H-s-triazole [3,4 -b] [3] benzazepine 11-ethylidene-3-methoxy-8-methyl-11H-s-triazole [3,4-b] [3] -benzazepine 3,8-dimethoxy-1 1-methylene-1 lH- s-triazole [3,4b] [3] benz azepine 3,9-dimethoxy-11-methylene-11H-s-triazole [3,4-b] benz azepine 3-methoxy-11H-s-triazole [3,4 -b] [3] benzazepin-11-one 3-ethoxy-11H-s-triazole [3,4-b] [3] benzazepin-11-one 3-ethoxy-6methyl-11H-s-triazole [3,4 -b] [3] benzazepin-11-one 8-chloro-3-methoxy-1 1H-s-triazole [3,4-b] [3] benzazepin-1 1-one

   8-chloro-3-ethoxy-11H-s-triazole [3,4-b] [3] benzazepin-11-one 3-ethoxy-8-methyl-11H-s-triazole [3,4-b] [3 ] benzazepin-11-one 3-iithoxy-8-methoxy-11 Hs-triazole [3,4-b] [3] benzazepin -11-one
According to the invention, the compounds (I) are prepared by processes A, B, C, D, E and F described below. 

 

  Procedure A
The compounds (I) are compounds of the formula:
EMI5. 1
 in which all symbols have the meanings given above, prepared by compounds of the formula:
EMI5. 2nd
 in which Q represents carbonyl or an acetalized carbonyl and the other symbols have the meanings given above, are subjected to the intramolecular cyclization. 



   In the above formula (II), the acetal group Q is a group of the formula:
EMI5. 3rd
 in the R8 and R9 lower alkyl radicals with about 1 to 3 carbon atoms (e.g. B.  Methyl, ethyl, propyl, etc. ) or R8t and R9 together are a lower alkylene radical with about 2 to 4 carbon atoms (e.g. B.  Form ethylene and propylene).   



   The reaction to cyclize compounds (II) to compounds (Ia) in this process normally takes place in the presence of an acid catalyst.  Suitable acid catalysts are, for example, mineral acids (e.g. B.  Hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid and perchloric acid), Lewis acids (e.g. B.  Aluminum chloride, titanium trichloride, tin trichloride and boron trifluoride), polyphosphoric acids and polyphosphoric acid esters. 



  In general, at least one molar equivalent of this acid, based on the compound (II), is used. 



  The reaction is usually carried out in a solvent.  Either any of the acids mentioned above for the cyclization reaction, which in this case are both a cyclizing agent and a solvent, or any other inert solvent which does not interfere with the reaction, can be used as the solvent.  For example, aromatic hydrocarbons (e.g. B.  Benzene, toluene and xylene) and halogenated aliphatic hydrocarbons (e.g. B.  Dichloromethane, dichloroethane, chloroform, carbon tetrachloride or tetrachloroethane) can be used.  The reaction is usually carried out at a suitable temperature between - 10 "and + 2000C.  In general, it is advantageous to carry out the reaction near room temperature. 

  If necessary, work can be carried out at elevated temperature. 



  Procedure B
The compounds (Ia) are also obtained by reacting compounds of the formula:
EMI6. 1
 in which all symbols have the meanings given above, with an alkylating or aralkylating agent. 



   In this process, the reaction of the compounds (III) to the compounds (Ia) is carried out with the aid of an alkylating or aralkylating agent.  As an alkylation or  Aralkylating agents can be used in any type of reagent provided they can introduce R6 into the mercapto group of compound (III).  Normally, preference is given to a dialkyl sulfate or diaryl sulfate of the formula: (R6) 2SO4 (IVa) in which R6 has the meaning given above, or an alkyl halide or aralkyl halide of the formula: R5X '(IVb) in which R6 has the meaning given above and X' is a halogen atom is similar to the substituent on ring A. 

  This reaction does not always have to be carried out in the presence of a solvent, but the alkylation or  Aralkylating agents are used in excess, so that it is also effective as a solvent.  Normally, however, this reaction is advantageously carried out in a suitable solvent, e.g. B.  an alcohol (e.g. B.  Methanol and ethanol), a hydrocarbon (e.g. B.     Benzene, toluene and xylene), dimethylformamide or dimethyl sulfoxide.  Good results are generally obtained when the mercapto group of compound (III) is first converted to an alkali salt before alkylation or aralkylation according to the invention. 



  To prepare such an alkali metal salt of compound (III), alkali metal hydroxides (e.g. B.  Sodium hydroxide or potassium hydroxide4), alkali alkoxides (e.g. B.  Sodium methoxide, potassium methoxide, sodium ethoxide, potassium ethoxide or potassium t-butoxide), alkali metal amides (e.g. B.  Sodium amide and potassium amide) or alkali metal hydrides (e.g. B.  Sodium hydride or lithium hydride) can be used.  The alkali compound is normally used in an amount of about 1 to 5 molar equivalents based on the compound (III).  The amount of alkalizing or  Aralkylating agent is usually preferably 1 to 5 equivalents based on the compound (III).  This reaction normally takes place at room temperature or a lower temperature, but it can be accelerated by carrying out the reaction at a suitable elevated temperature. 



  Procedure C
The compounds (I) are compounds of the formula:
EMI6. 2nd
 in which all symbols have the meanings given above, by oxidation of compounds of the formula:
EMI6. 3rd
 in which all symbols have the meanings given above.    



   In this process, the reaction is carried out using an oxidizing agent.  Any reagents which are capable of oxidizing a thioether group are suitable as oxidizing agents.  Usually hydrogen peroxide, organic peracids (e.g. B.     Performic acid, peracetic acid.  Perbenzoic acid or m-chloroperbenzoic acid), permanganoic acid salts (e.g. B.  Potassium permanganate, sodium permanganate).  Halogens (e.g. B.  Chlorine and bromine) or active organic halogen compounds (N-bromosuccinimide or N-chlorosuccinimide) can be used successfully.  Usually this reaction is advantageously carried out in a suitable solvent, e.g. B.  Water, alcohol (e.g. B.  Methanol, ethanol or propanol), organic carboxylic acids (e.g. B.  Formic acid or acetic acid), halogenated hydrocarbons (e.g. B.  Dichloromethane or chloroform), aromatic hydrocarbons (e.g. B. 

  Benzene, toluene or xylene), tetrahydrofuran or dioxane.   



   There are cases where, depending on the type of oxidizing agent, this reaction is more advantageously carried out in the presence of an acid or a base.  Suitable acids are usually mineral acids (e.g. B.  Hydrochloric acid, hydrobromic acid, sulfuric acid and phosphoric acid) or organic acids (e.g. B.  Formic acid and acetic acid).  Suitable bases are, for example, alkali metal hydroxides (e.g. B.  Sodium hydroxide and potassium hydroxide) and tertiary amines (e.g. B.  Trimethylamine, triethylamine and pyridine). 



   In this reaction, either the compound of formula (Ib), in which n is 1, or the compound (Ib), in which n is 2, can be selectively prepared by selecting the appropriate type and amount of the oxidizing agent, the reaction temperature and other reaction parameters .  Usually, when the reaction is carried out at a temperature not higher than room temperature using the oxidizing agent in an amount of 1 molar equivalent of active oxygen per mol of the compound (Ia '), the compound (Ib) in which n is 1 is usually formed while the compound (Ib) in which n is 2 is normally formed when the oxidizing agent is used in excess. 



   This reaction is usually carried out at a temperature between -20 "and + 1500C.  In many cases the reaction is generally smooth near room temperature.  The reaction can optionally be carried out at elevated or reduced temperature. 



     Procedure D
The compounds (I) are compounds of the formula:
EMI7. 1
 in which all symbols have the meanings given above, by reacting compounds of the formula:
EMI7. 2nd
 in which Y is a halogen or a group of the formula -S (O) "R6, in which R6 and n have the meanings given above and the other symbols have the meanings mentioned above, with an alcoholate of the formula:
R7-OM (VI), in which M is an alkali metal and R7 has the meaning given above. 



   In formula (V) the halogen atom Y can be, for example, chlorine, bromine or iodine.  Examples of suitable alkali metals M are sodium or potassium. 



   In this process, the compound (V) is reacted with the compound (VI) to give the desired compound (Ic).  The reaction is usually carried out in the presence of a solvent.  Any solvents that do not interfere with the reaction are suitable.  An alcohol which contains the same radical R as the alcoholate (VI) used as reactant is preferably used as the solvent.  As examples are methanol, ethanol, propanol, isopropanol butanol, sec. -Butanol and t-Butanol to name.  Other solvents that are inert in the reaction, e.g. B.  aromatic hydrocarbons (e.g. B.  Benzene, toluene and xylene) or ether (e.g. B.  Diethyl ether, isopropyl ether, tetrahydrofuran and dioxane) can be used.  Preferably 1 mole of compound (V) is reacted with not less than 1 mole to about 10 moles of compound (VI). 

  The reaction is usually carried out at temperatures between - 100 and +200 C and generally suitably at a temperature around the boiling point of the solvent used. 



  Procedure E
The compounds (I) are compounds of the formula: 
EMI7. 3rd




  in which all symbols have the meanings given above, by oxidation of compounds of the formula (Ia) in which R3 and R4 are hydrogen. 



   The reaction in this process is carried out using an oxidizing agent, e.g. B.  Selenium dioxide. 

 

  Procedure F
The compounds (I) are compounds of the formula:
EMI7. 4th
 in which all symbols have the meanings given above, by reacting compounds of the formula (Ia) in which R3 and R4 are hydrogen with an aldehyde of the formula R5.     CHO, wherein R5 has the meaning given above. 



   This reaction is generally carried out in the presence of a base, e.g. B.  an alkali hydroxide (e.g. B.  Sodium or potassium hydroxide) or of triethylamine or trimethylbenzylammonium hydroxide. 



   The compounds (Ia), (Ia "), (Ia" '), (Ib) and (Ic), i. H. 



  the desired compounds (I) can be used as products with the desired degree of purity according to known separation and purification processes, e.g. B.  Concentration, concentration, extraction, chromatography and recrystallization can be isolated.  The compounds (I) can also be used as physiologically acceptable salts, e.g. B.  as salts of mineral acids, by treatment with the corresponding inorganic acid (e.g. B.  Hydrochloric acid, hydrobromic acid and sulfuric acid) can be obtained. 



   The compounds (I) and their salts which can be prepared in the above-mentioned manner have activities as muscle relaxants, analgesics, anti-inflammatory agents, antipyretics and other activities in animals, in particular in mammals (e.g. B.  in humans, dogs, rabbits, rats and mice) and are therefore valuable as muscle relaxants, analgesics, anti-inflammatory agents and remedies for the therapy and relief of myalgia and other diseases.  When the compounds (I) and their salts are used as medicaments for these purposes, they can safely be taken orally or paranterally either as such or in admixture with pharmaceutically acceptable inert carriers in suitable medicinal forms such as powders, granules, tablets, capsules, solutions for injection, suppositories etc.  be administered. 

  The correct dosage of the compounds (I) or their salts depends on factors such as the route of administration, symptoms and severity of the disease, but when used as analgesics for the treatment of myalgia they are usually administered in a daily dose of about 10 mg to about 250 mg for the Administered to adults orally. 



   The analgesic effects of some representative compounds (I) are listed in Table 1 below. 



   TABLE 1 Analgesic Effect (Mouse, Acetic Acid Pain Curvature Method)
EMI8. 1
 Compounds ED5o (950Jo confidence limit), mg / kg oral (I ') Z = SEC, 10.5 (6.3-17.3) (I') Z = SOCH3 10.3 (5.6-19.0 )
The compounds (I) are not only valuable as such as drugs, but are also suitable as intermediates for the synthesis of drugs.  For example, the compounds (Ia), (Ia "), (Ia" ') or (Ib) by treatment with acid or alkali in keto compounds (VII) or with the aid of a desulfurizing agent (e.g. B.  Raney nickel) can be converted into compounds (VIII) as illustrated by the following reaction scheme:
EMI8. 2nd

Here all symbols have the meanings mentioned above. 



   The aforementioned compounds (VII) and (VIII) have analgesic effects, a slackening effect on the muscles, anti-inflammatory and other pharmacological effects and are valuable as medicaments, e.g. B.  as analgesics, muscle relaxants etc.  (see DT-OS 2442 987). 



   The starting compounds for processes A, B and D described above can be prepared, for example, as follows:
EMI9. 1
   Here R stands for a lower alkyl radical and X 'and V' for halogen atoms, while the other symbols have the meanings given above. 



   As the reaction scheme (a) shows, a phenylacetic acid hydrazide derivative of the formula (IX) is reacted with an isothiocyanate compound of the formula (X) or a mixed anhydride of the dithiocarbamic acid carbonic acid ester of the formula (X ').  This reaction is carried out without a solvent or normally in the presence of a solvent (e.g. B.  Water, alcohols, tetrahydrofuran or benzene) at a temperature from room temperature to the boiling point of the solvent used.  In this reaction, a thiosemicarbazide derivative of the formula (XI) is obtained.  Compound (XI) can be isolated, but normally the reaction mixture containing compound (XI) is subjected to the next cyclization reaction.  For example, the compound (XI) is cyclized by treatment with alkali. 

  This cyclization is normally carried out using a metal hydroxide (e.g. B. 



  Sodium hydroxide or potassium hydroxide) with an aqueous solvent or an alcoholate (e.g. B.  Sodium or potassium methoxide or ethoxide) with the appropriate alcohol.  The reaction proceeds at temperatures from room temperature to the boiling point of the solvent used.  The reaction leads to the triazole derivatives (XII) and their tautomers (XII '). 



   By reaction with an alkyl halide (or aralkyl halide) in the presence of an alkali base (e.g. B.  Sodium hydroxide, potassium hydroxide, sodium methoxide, potassium methoxide, sodium ethoxide or potassium ethoxide) normally in a solvent, preferably an anhydrous solvent, e.g. B.  an alcohol (for example methanol or ethanol) are made from the compounds (XII) or  (XII ') the starting compounds (II) are obtained. 



   The starting compounds (III) can be prepared, for example, by the process described in DT-OS 2442 987 by the applicant in the manner shown in reaction scheme (b).  Note that the compound (III ') is a tautomeric form of the compound (III). 



   The compounds (V '), i. H.  the compounds (V) in which Y is a halogen atom can be obtained by reacting the compounds (VIII) with a halogenating agent (e.g. B. 



  Chlorine, bromine or N-bromosuccinimide) can be prepared in the manner shown in reaction scheme (c). 



   The invention is explained in detail by the following reference examples and exemplary embodiments. 



   Reference Example I
A mixture of 2.3 g of phenylacetic acid hydrazide and 2.8 g of 2,2-diethoxyethyl isothiocyanate in 30 ml of ethanol was heated to 900 ° C. for 5 minutes on a water bath and then left to stand at room temperature for 30 minutes.  The solvent was evaporated and the residue treated with n-hexane.  The crystals of 4- (2. 2-Diethoxyethyl) -1 -phenylacetylthiosemicarbazid were recrystallized from ethanol-n-hexane and aqueous ethanol in this order.  Colorless needles of melting point 93-940C were obtained. 



  Elemental analysis for: C15H23N303S calculated: C 55.36 H 7.12 N 12.91 found: C 55.45 H 7.26 N 12.61
Reference Example 2
3.25 g of the 4- (2,2-diethoxyethyl) -1-phenylacetylthiosemicarbazide prepared according to Reference Example 1 were added to 20 ml of an aqueous 2N potassium hydroxide solution. 



  The mixture was heated to 95 ° C on the water bath for 15 minutes, after which 2.4 g of ammonium chloride were added while cooling with ice.  The crystalline 3-benzyl-4- (2,2-diethoxyethyl) -4H-1,2,4-triazol-5-thione obtained was filtered off.  Recrystallization from aqueous ethanol gave colorless crystals with a melting point of 87-880C. 



  Elemental analysis for: C, 5H2lN302S calculated: C 58.60 H 6.89 N 13.67 found: C 58.50 H 6.93 N 13.77
Reference example 3
0.307 g of the 3-benzyl-4- (2,2-diethoxyethyl) -4H -1,2,4-triazol-5-thione prepared according to Reference Example 2 was dissolved in 3 ml of methanol.  0.6 ml of a 2N solution of sodium methoxide in methanol was added to the solution.  While stirring, 0.07 ml of methyl iodide was added dropwise.  After 30 minutes the methanol was evaporated. 



  The residue was diluted with water and extracted with chloroform.  The chloroform layer was washed with water and dried over Na3SO4.  Evaporation of the solvent gave 3-benzyl-4- (2,2-diethoxyethyl) -5- -methylthio-4H-1,2,4-triazole in the form of an oil (quantitative yield). 



  NMR: 8 (CDCl3) 1.20 (6H, t), 2.75 (3H, s), 3.50 (4H, d-q),
3.80 (2H, d, J = 5Hz), 4.30 (2H, s), 4.40 (1H, t, J = 5Hz),
7.30 (4H). 



  Elemental analysis for: C, 6H33N302S calculated: C 59.78 H 7.21 N 13.07 found: C 59.26 H 7.15 N 12.99
Reference example 4
In the manner described in Reference Example 3, 3-benzyl-4- (2,2-diethoxyethyl) -4H- 1,2,4-triazol-5-thione was converted into 3-benzyl-4- (2,2-diethoxyethyl) - Obtained 5-ethylthio-4H-1,2,4-triazole in the form of an oil. 



  NMR: 8 (CDCl3) 1.20 (6H, t, J = 7Hz), 1.45 (3H, t, J = 8Hz),
3.10-3.80 (6H, m), 3.80 (2H, d, J = 5Hz), 4.30 (2H, s),
4.40 (1H, t, J = 5Hz), 7.25 (4H, s). 



   Reference Example 5
To a solution of 1.9 g of aminoacetone ethylene acetal in 26 ml of tetrahydrofuran was added 1.7 ml of triethylamine with stirring, after which 0.8 ml of carbon disulfide was added dropwise.  After 10 minutes, 1.3 ml of ethyl chlorocarbonate was added dropwise.  The mixture was stirred at room temperature for 20 minutes.  The solvent was evaporated and the residue extracted with chloroform.  The chloroform layer was washed with water and dried over Na2SO4.  The solvent was evaporated and the oily residue was dissolved in 20 ml of benzene.  After adding 1.7 g of phenylacetic acid hydrazide, the solution was refluxed for 10 minutes. 

 

  The solvent was then evaporated.  This was 4- (2,2-ethylenedioxypropyl) -1 -phenylacetylthiosemicarbazid
EMI10. 1
 obtained in the form of an oil.  To this oil was added 20 ml of a 2N potassium hydroxide aqueous solution.  The mixture was heated to 90 ° C on the water bath for 15 minutes. 



  After cooling, 2.6 g of ammonium chloride were added.  The precipitate was filtered off.  The crystals of 1 - (3-benzyl-1,5-dihydro-5-thioxo-4H-1,2,4-triazol-4-yl) -2-propanoneethylene acetal obtained in this way were recrystallized from aqueous methanol.  Colorless prisms with a melting point of 119-120 ° C. were obtained.   



     A rnrw2 analysis for: C14Hl7N302S calculated: C 57.71 H 5.88 N 14.42 found: C 57.82 H 5.79 N 14.50
Reference example 6
To 10 ml of ethanol were added 1.1 g of the 1- (3-benzyl-1,5-dihydro-5-thioxo-4H- - 1, 2,4-triazol-4-yl) -2-propanoneethylene acetal prepared according to Reference Example 5 added, followed by the addition of 5.0 ml of 2N hydrochloric acid.  The mixture was refluxed for 40 minutes and then concentrated to half its original volume.  Water was added to the concentrate.  The precipitate formed was filtered off.  1- (3-Benzyl-1,5-dihydro-5-thioxo- -4H-1, 2,4-triazol-4-yl) -2-propanone was obtained in the form of crystals.  Recrystallization from ethyl acetate gave colorless needles melting at 163-1 650C. 



     Elencentaz analysis for: Cl2Hl3N3OS calculated: C 58.27 H 5.30 N 16.99 found: C 58.51 H 5.22 N 17.13
Reference Example 7
In the manner described in Reference Example 3, 1- (3-benzyl-1,5-dihydro-5-thioxo-4H-1,2,4-triazol-4-yl) -2-propanone was converted to 1- (3-benzyl -5-methylthio-4H-1,2,4-triazol-4-yl) -2-propanone obtained in the form of crystals.  Colorless prisms with a melting point of 113-114 ° C. were obtained by recrystallization from ethyl acetate. 



     Elemental analysis for: Cl3HlsN3OS calculated: C 59.74 H 5.79 N 16.08 found: C 59.68 H 5.72 N 16.21
Reference Example 8
In the manner described in Reference Example 1, 4- (2nd 2-Diethoxyäthyl) - 1 - (x-methylphenylacetyl) thiosemi- carbazid obtained from methylphenylacetic acid hydrazide.  The product was in the form of colorless prisms with a melting point of 105-1060C (after recrystallization from aqueous methanol). 



     E1etieii tauztialyse for: Cl6H25N303S calculated: C 56.61 H 7.42 N 12.38 found: C 56.38 H 7.40 N 12.42 reference example 9
In the manner described in Reference Example 2, 4- (2,2-diethoxyethyl) -1 - (a-methylphenylacetyl) thiosemicarbazide 4- (2,2-diethoxyethyl) -3 - (α-methylbenzyl) -4H- Obtained 1,2,4- -triazol-5-thione in the form of an oil. 



   Reference example 10
In the manner described in Reference Example 3, 4- (2,2-diethoxyethyl) -3 - (α-methylbenzyl-4H-1,2,4-triazol-5-thione became 4- (2,2-diethoxyethyl ) -3 - (α-methylbenzyl) -5-methylthio-4H-l, 2,4-triazole in the form of an oil. 



   Reference Example 11
In the manner described in Reference Example 1, 1 - (4-chlorophenylacetyl) -4- (2,2-diethoxyethyl) thiosemicarbazide was obtained from 4-chlorophenylacetic acid hydrazide in the form of colorless needles with a melting point of 107-1090C (after recrystallization from ethanol). 



  Elemental analysis for: C15H22CIN3O3S calculated: C 50.06 H 6.16 N 11.68 found: C 50.28 H 6.14 N 12.09 reference example 12
In the manner described in Reference Example 2, I - (4-chlorophenylacetyl) -4- (2,2-diethoxyethyl) thiosemicarbazide and 2N sodium hydroxide became 3- (4-chlorobenzyl) -4- (2nd 2 -Diethoxyäthyl) -4H-1,2,4-triazol-5-thione as colorless needles of melting point 164-165 C (after recrystallization from methanol). 



  Elemental analysis for: C15H20ClN302S calculated: C 52.70 H 5.90 N 12.29 found: C 52.77 H 5.97 N 12.28
Reference Example 13
3- (4-Chlorobenzyl) -4- (2,2-diethoxyethyl) -4H- 1,2,4 -triazol-5-thione was converted into 3- (4-chlorobenzyl) -4- in the manner described in Reference Example 3 Obtained (2,2-diethoxyethyl) -5-methylthio-4H-1,2,4-triazole in the form of an oil. 



   Reference Example 14
From diphenylacetic acid hydrazide, 1-diphenylacetyl-4- (2,2-diethoxyethyl) thiosemicarbazide was obtained in the form of crystals in the manner described in Reference Example 1.  Recrystallization from ethanol gave colorless needles melting at 151-1520C. 



  Elemental analysis for: C21H27NsO3S calculated: C 62.81 H 6.78 N 10.47 found: C 63.07 H 6.80 N 10.54
Reference Example 15
1-Diphenylacetyl-4- (2,2-diethoxyethyl) thiosemicarbazide became 4- (2,2-diethoxyethyl? -3-diphenylmethyl-4H-1,2,4-triazole-5) in the manner described in Reference Example 2 - -thion obtained in the form of crystals.  Recrystallization from ethyl acetate-n-hexane gave colorless needles with a melting point of 155-1560C.    



  Elemental analysis for: C21H25N302S calculated: C 65.77 H 6.57 N 10.96 found: C 65.82 H 6.58 N 10.93
Reference Example 16
In the manner described in Reference Example 3, 4- (2,2-diethoxyethyl) -3-diphenylmethyl-4H-1,2,4-triazole -5-thione was 4- (2,2-diethoxyethyl) -3-diphenylmethyl- 5-methyl-thio-4H-1,2,4-triazole obtained in the form of crystals.  Recrystallization from acetone-n-hexane gave colorless
Prisms with melting point 80-81 C obtained. 



  Elemental analysis for: C22H27N302S calculated: C 66.47 H 6.85 N 10.57 found: C 66.76 H 6.72 N 10.44
Reference Example 17
In the manner described in Reference Example 1, 4- (2,2-diethoxyethyl) -1- (4-methylphenylacetyl) thiosemicarbazide was obtained in the form of crystals from 4-methylphenylacetic acid hydrazide.  Colorless needles of melting point 122 were obtained by recrystallization from aqueous ethanol
Received 123 C. 

 

     Elemental analysis for: Cl6H2sN303S calculated: C 56.61 H 7.42 N 12.38 found: C 56.07 H 7.38 N 12.38
Reference Example 18
In the manner described in Reference Example 2, 4- (2,2-diethoxyethyl) -1 - (4-methylphenylacetyl) thiosemicarbazide became 4- (2,2-diethoxyethyl) -3- (4-methylbenzyl) -4H-1,2 , 4- triazol-5-thione in the form of crystals. 

  Recrystallization from aqueous ethanol gave colorless needles with a melting point of 110-11 10C, elemental analysis for: C16H23N1O2S calculated: C 59.78 H 7.21 N 13.07 found: C 59.80 H 7.14 N 13.21
Reference Example 19
In the manner described in Reference Example 3, 4- (2,2-diethoxyethyl) -3- (4-methylbenzyl) -4H- 1,2,4-tri azole-5-thione was converted to 4- (2,2-diethoxyethyl) -3- (4-methylbenzyl) -5-methylthio-4H-1,2,4-triazole obtained in the form of an oil. 



   NMR: 8 (CDCl3) 1.30 (6H, t), 2.45 (3H, s), 2.85 (3H, s),
3.20-4.05 (4H, m), 3.90 (2H, d), 4.40 (2H, s), 4.45 (1H, t), 7.25 (4H, s). 



   Reference Example 20
In the manner described in Reference Example 1, 4- (2,2-diethoxyethyl) -1- (4-methoxyphenylacetyl) thiosemicarbazide was obtained in the form of crystals from 4-methoxyphenylacetic acid hydrazide.  After recrystallization from ethanol, colorless needles of melting point 120-121 "C were obtained. 



   Elemental analysis for: Cl6H2sN304S calculated: C 54.06 H 7.09 N 11. 82 found: C 53.80 H 7.12 N 11.62 Reference Example 21
In the manner described in Reference Example 2, 4- (2,2-diethoxyethyl) -1 - (4-methoxyphenylacetyl) thiosemicarbazide 4- (2,2-diethoxyethyl) -3- (4-methoxybenzyl) -4H -1 , 2,4-triazol-5-thione in the form of crystals.  By
Recrystallization from aqueous ethanol became colorless
Obtain needles of melting point 115-1 160C. 



   Elemental analysis for: C, 6H23N303S calculated: C 56.95 H 6.87 N 12.45 found: C 56.97 H 6.82 N 12.58
Reference Example 22
In the manner described in Reference Example 3, 4- (2,2-diethoxyethyl) -3- (4-methoxybenzyl) -4H- 1,2,4-tri azole-5-thione was 4- (2,2-diethoxyethyl) -3- (4-methoxybenzylmethylthio-4-H-1,2,4-triazole obtained in the form of an oil. 



   NMR: 8 (CDCl3) 1.30 (6H, t), 2.85 (3H, s), 3.10-4.00 (6H, m), 3.90 (3H, s), 4.35 ( 2H, s), 4.50 (1H, t), 6.80-7.60 (4H, m). 



   Reference Example 23
In the manner described in Reference Example 1, 4- (2,2-diethoxyethyl) -1 - (3-methoxyphenylacetyl) thiosemicarbazide would be obtained in the form of crystals from 3-methoxyphenylacetic acid azide.  Colorless needles of melting point 109 111 ° C. were obtained by recrystallization from aqueous methanol. 



  Elemental analysis for: C16H2N3O4S: Calculated: C 54.06 H 7.09 N 11.82 Found: C 53.74 H 6.88 N 12.07
Reference Example 24
In the manner described in Reference Example 2, 4- (2,2-diethoxyethyl) - 1 - (3-methoxyphenylacetyl) thiosemicarbazide 4- (2,2-diethoxyethyl) -3 - (3-methoxybenzyl) -4H- - Obtained 1,2,4-triazol-5-thione in the form of crystals.  Recrystallization from aqueous methanol gave colorless needles with a melting point of 67-69 ° C.    



  Elemental analysis for: C16H23NsO3S calculated: C 56.95 H 6.87 N 12.45 found: C 56.64 H 6.75 N 12.46
Reference Example 25
In the manner described in Reference Example 3, the product prepared according to Reference Example 24 was used
Obtained 4- (2,2-diethoxyethyl) -3- (3-methoxybenzyl) -5-methylthio-4H -1,2,4-triazole in the form of an oil. 



   NMR: Ï (CDCl3) 1.20 (6H, t), 2.75 (3H, s), 3.20-3.80 (4H, m), 3.75 (3H, s), 3.75 ( 2H, d), 4.30 (2H, s), 4.35 (1H, t),
6.70-7.40 (4H, m). 



   Reference Example 26
0.2 g of potassium hydroxide and then 0.23 g of 3-methylthio-l 1H-s-triazole [3,4-b] [3] benzazepine were added to 2 ml of ethylene glycol.  The mixture was at 150 to 2 hours
160 C stirred, whereupon water was added.  The mixture was acidified with 4N hydrochloric acid and extracted with chloroform.  The chloroform layer was washed with water and dried over Na2SOg.  The solvent was evaporated and the residue treated with ethyl acetate.  This gave 2,1 1-dihydro-3H-s-triazole [3,4-b] [3] - benzazepin-3-one in the form of crystals. 

  Recrystallization from methanol gave light brown needles with a melting point of 207-208 "C.     The following compounds were prepared in a manner similar to that described in this reference example 11-methyl-3-methylthio-11 H-s-triazole [3, 4-b] [3] benzazepine was treated with potassium hydroxide.  The reaction mixture was worked up in the manner described. 



  This gave 2,11-dihydro-ll-methyl-3H-s-triazole [3,4-b] - [3] benzazepin-3-one in the form of crystals.  The product had the form of pale brown needles (after recrystallization from ethanol) with a melting point of 119 120 ° C.    



   3-Methylthio-11-phenyl-11 H-s-triazole [3,4-b] [3] benzazepine was treated with potassium hydroxide.  The reaction mixture was worked up in the manner described. 



  2,11-Dihydro-ll-phenyl-3H-s-triazole [3,4-b] - [3] benzazepin-3-one was obtained in the form of crystals.  Recrystallization from methanol gave colorless needles melting at 258-2600C. 



   From 8-chloro-3-methylthio-1 1H-s-triazole [3. 4-b] [3] benzazepine, 8-chloro-2, 11-dihydro-3H-s-triazole [3,4-b] [3] benzazepin-3-one was obtained in the form of crystals.  The product was in the form of colorless platelets (after recrystallization from chloroform-methanol) with a melting point of 281-283 C.    



   8-Methyl-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine became 2,11-dihydro-8-methyl-3H-s-triazole [3,4-b] [3 ] benzazepin-3-one obtained in the form of crystals.  Recrystallization from chloroform-methanol gave colorless platelets melting at 232-2340C. 



   9-Methoxy-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine became 2,11-dihydro-9-methoxy-3H-s-triazole [3,4-b] [3 ] benzazepin-3-one obtained in the form of crystals.  Recrystallization from chloroform-methanol gave colorless needles with a melting point of 271-274 "C.    

 

   Reference Example 27
10 ml of 2N potassium hydroxide was added to 2.3 g of 8-chloro-3-methylsulfonyl-IIH-s-triazole [3,4-b] - [3] benzazepine in 20 ml of dioxane.  The mixture was heated on the water bath at 95 C for 30 minutes.  The solvent was evaporated and water was added to the residue. 



  The mixture was acidified with 2N HCl.  The crystalline precipitate obtained was filtered off and dried.  8-Chloro-2,11-dihydro-3H-s-triazole [3,4-b] [3] benzazepin-3-one was obtained in the form of crystals.  Recrystallization from chloroform-methanol gave colorless platelets with a melting point of 281-283 C.    



     Learning tar analysis for: C11H, ClN3O calculated: C 56.65 H 3.45 N 17.99 found: C 56.30 H 3.25 N 17.83
Reference Example 28
In the manner described in Reference Example 27, 8-methyl-3-methylsulfonyl-1 Hs-triazole [3, 4-b] [3] benzazepine 8-methyl-2, 1 1-dihydro-3H-s-triazole [3 , 4-b] [3] benzazepin-3-one obtained in the form of crystals.  Recrystallization from chloroform-methanol gave colorless platelets with a melting point of 232-234 "C.    



  Elemental analysis for: Cl2H, IN3O calculated: C 67.59 H 5.20 N 19.71 found: C 67.31 H 5.10 N 19.80
Reference Example 29
0.245 g of 3-methylsulfinyl-1 lH-s-triazole [3,4-b] [3] benzazepine was added to 3 ml of 80% phosphoric acid.  The mixture was heated on the oil bath at 130-140 "C for 1 hour.  After adding water, the crystals were filtered off and dried.  This gave 2,1 1-dihydro-3H-s-triazole [3,4-b] [3] benzazepin-3-one.  Recrystallization from chloroform-methanol gave colorless needles with a melting point of 210-2110C.    



   Reference Example 30
In the manner described in Reference Example 29, 8-methyl-3-methylsulfinyl-11 Hs-triazole [3,4-b] [3] benzazepine 2,11 -dihydro-8-methyl-3H-s-triazole [3, 4-b] [3] benzazepin-3-one obtained in the form of crystals.  Recrystallization from chloroform-methanol gave colorless platelets melting at 233-2340C. 



   Reference Example 31
6 ml of Raney nickel (wet) were added to 1.15 g of 3-methylthio-IIH-s-triazole [3,4-b] [3] benzazepine in 20 ml of ethanol.  The mixture was refluxed with stirring for 15 minutes.  The Raney nickel was filtered off and the solvent was separated from the filtrate.  Water was added to the residue.  Here, 1 1H-s-triazole [3,4-b] - [3] benzazepine was obtained in the form of crystals.  Recrystallization from ethanol-n-hexane gave colorless needles with a melting point of 157-1580C.  The infrared spectrum was identical to the spectrum of the same compound obtained by reacting 2-hydrazine-3-benzazepine with the o-formic acid ester. 



   The following compound was made by a procedure similar to that described in this reference example:
3-Methylthio-11-phenyl-11H-triazole [3,4-b] [3] benzazepine was treated with Raney nickel in the manner described.  Here, ll-phenyl-1 1H-s-triazole [3,4-b] [3] - benzazepine was obtained in the form of crystals.  Recrystallization from ethanol gave colorless prisms with a melting point of 217-218 "C.    



     Reference Example 32
To 1.83 g of 11H-s-triazole [3,4-b] [3] benzazepine in 40 ml of chloroform was added 0.1 ml of pyridine, and 0.55 ml of bromine was added dropwise with stirring.  The mixture was stirred for 2 hours and then washed with water and dried over Na2SO4.  After evaporation of the solvent, the residue was treated with ether.  This gave 3-bromo-IIH-s-triazole [3,4-b] [3] benzazepine in the form of crystals.  These crystals were recrystallized from ethanol and methanol in this order to obtain pale brown platelets with a melting point of 169-1700C. 



     Ele ientara, ialyse for: CllH8BrN3 calculated: C 50.40 H 3.08 N 16.03 found: C 50.87 H 3.12 N 15.78
example 1
12 ml of 2N sodium methoxide / methanol were added to a solution of 6.15 g of 3-benzyl-4- (2,2-diethoxy-ethyl) -4H-1,2,4-triazol-5-thione in 36 ml of methanol. whereupon 1.48 ml of methyl iodide was added with stirring.  The reaction mixture was then worked up in the manner described in Reference Example 3, whereby 3-benzyl-4- (2,2-di ethoxyethyl) -5-methylthio-1,2,4-triazole was obtained in the form of an oil (almost quantitative yield ).  To the total amount of this oily product was added 40 ml of a 70% aqueous solution of perchloric acid.  The mixture was heated to 80 to 90 ° C.  After 25 minutes, ice water was added to the mixture, whereupon an oil separated. 

  The supernatant liquid was removed by decantation, and the residue was neutralized by adding a saturated aqueous sodium hydrogen carbonate solution and extracted with chloroform.  The chloroform layer was washed with water and dried over Na2SO4.  The solvent was evaporated and the residue treated with ethyl acetate.  The crystals of 3-methylthio-11H-s-triazole [3,4-b] [3lbenz-azepine formed in this way were recrystallized from methanol.  Colorless needles of melting point 1 68-1690C were obtained. 



  Elemental analysis for: Cl2HllN3S calculated: C 62.85 H 4.84 N 18.33 found: C 62.86 H 4.70 N 18.61
Example 2
11.0 g of sodium were dissolved in 11% methanol.  134.4 g of 3-benzyl-4 (2,2-diethoxyethyfl-4H-1,2,4-triazole-5-thione were added to the solution.  Then 30.0 ml of methyl iodide was added dropwise and the mixture was stirred for 20 minutes.  The reaction mixture was then worked up in the manner described in Reference Example 3, 140 g of 3-benzyl-4- (2,2-diethoxyethyl) -5-methylthio-1,2,4-triazole being obtained in the form of an oil. 



  This oil was gradually added to 430 ml of concentrated sulfuric acid previously cooled with ice sodium chloride.  The mixture was then stirred at room temperature for 30 minutes and then poured into 5 liters of ice water.  The mixture was neutralized with concentrated aqueous ammonia.  The crystals formed in this way were filtered off.  The crystalline 3-methylthio-1 1H-s- -triazole [3,4-b] [3] benzazepine obtained was recrystallized from methanol.  Colorless needles with a melting point of 168-1690C were obtained.  The infrared spectrum of this product was identical to the spectrum of the product produced according to Example 1. 



   Example 3
To 10 ml of concentrated sulfuric acid, which had previously been cooled with ice-sodium chloride, was added 3. 2 g of the 3-benzyl-4- (2,2-di ethoxyethyl) -5-ethylthio-4-H-1, 2,4-triazole prepared according to reference example 4.  The mixture was left at room temperature for 15 minutes and then worked up in the manner described in Example 2.  The 3-ethylthio-1H-s-triazole- [3,4-b] [3] benzazepine obtained was recrystallized from ethyl acetate. 

 

  Colorless prisms with a melting point of 9495 C were obtained. 



  Elemental analysis for: Cl3Hl3N3S calculated: C 64.17 H 5.39 N 17.27 found: C 64.09 H 5.29 N 17.40
Example 4
15.0 g of polyphosphoric acid were added to 0.3 g of the 1- (3-benzyl-5-methylthio-4H-1,2,4-triazol-4-yl) -2-propanone prepared according to Reference Example 7.  The mixture was heated on an oil bath at 160-170 ° C for 4 hours.  The reaction mixture was poured into ice water, neutralized with concentrated aqueous ammonia and extracted with chloroform.  The chloroform layer was washed with water and dried over Na2SO4.  The solvent was evaporated and the residue treated with isopropyl ether.  Here, 6-methyl-3-methylthio-IIH-s-triazole- [3,4-b] [3] benzazepine was obtained in the form of crystals. 

  Recrystallization from ethyl acetate gave colorless platelets with a melting point of 129-130 "C.    



  Elemental analysis for: Cl3Hl3N3S calculated: C 64.17 H 5.39 N 17.27 found: C 64.09 H 5.27 N 17.25
Example 5
To cold concentrated sulfuric acid, 12.5 g of the 4- (2,2-diethoxyethyl) -3 - (α-methylbenzyl) -5-methylthio-4H-1,2,4-triazole prepared according to Reference Example 10 were added.  The cyclization reaction mixture was worked up in the manner described in Example 2.  11-Methyl-3-methylthio-11H-s-triazole [3, 4-b] [3] benzazepine was obtained in the form of an oil. 



  NMR: ô (CDCl3) 1.70 (3H, d), 2.80 (3H, s), 4.45 (1H, q),
6.75 (2H, d-d), 7.40 (4H). 



   Example 6
To the total amount of 1.7 g of 3- (4-chlorobenzyl) -4 - (2,2-diethoxyethyl) -4H- 1,2,4-triazole according to the reference example
13 ml of 3- (4-chlorobenzyl) -4- (2,2-diethoxyethyl) -5-methylthio-4H-1,2,4-triazole were added to 10 ml of 70% aqueous perchloric acid.  The cyclization reaction was
1.3 / 4 hours at 90-95 "C in the manner described in Example 1.  The reaction mixture was worked up in the manner described in Example 1, 8-chloro-3-methylthio-1 lH-s-triazole [3,4-b] [3] benzazepine being obtained in the form of crystals.  Recrystallization from methanol gave colorless needles with a melting point of 166-167 ° C.    



  Elemental analysis for: Cl2HloCIN3S calculated: C 54.64 H 3.82 N 15.93 found: C 54.62 H 3.71 N 16.18
Example 7
In the manner described in Example 1, 20.0 g of 4- (2,2-diethoxy-ethyl) -3-diphenylmethyl-5-methylthio-4H-1,2,4-triazole prepared in accordance with Reference Example 16 to 50 ml 70% aqueous perchloric acid solution with cooling with ice.  The mixture was heated to 60 65OC for 20 minutes.  The cyclization reaction mixture was worked up as described, whereby 3-methylthio-11-phenyl-1 1H-s-triazole [3,4-bj [31benzazepine was obtained in the form of crystals.  Recrystallization from ethanol gave colorless platelets with a melting point of 169-1700C. 



  Elemental analysis for: Cl8HlsN3s calculated: C 70.79 H 4.95 N 13.76 found: C 71.10 H 4.89 N 14.05
Example 8
0.215 g of 2,1 1-dihydro-3H-s-triazole [3,4-b] [3] benzazepin-3-thione was added to 3 ml of methanol.  0.6 ml of 2N sodium methoxide / methanol was added with stirring. 



  Then 0.07 ml of methyl iodide was added dropwise.  After 20 minutes the reaction mixture was extracted with ethyl acetate.  The ethyl acetate layer was washed with water and dried over Na2SOç.  The solvent was then evaporated and the residue treated with ether.  Here, 3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals.  Recrystallization from methanol gave colorless needles, melting point 168-1 690C.    



  This product was identical to the products produced according to Examples 1 and 2. 



   The following compound was prepared by a procedure similar to that described in this example:
By reacting 2,1 1-dihydro-3H-s-triazole [3,4-b] - [3] benzazepin-3-thione with benzyl bromide in the presence of sodium methoxide, 3-benzylthio-11 Hs-triazole [3,4 -b] - [3lbenzazepine obtained. 



  NMR: 8 (CDCl3) 4.05 (2H, s), 4.35 (2H, s), 6.55 (2H, d-d),
7.05-7.55 (9H, m). 



   Example 9
3- (4-Chlorobenziv-4- (2,2-diethoxyethyl) -4H- 1,2,4 -triazol-5-thione was converted into 3- (4-chlorobenzyl) -4- ( Obtained 2,2-diethoxyethyl) -5-methylthio-4H-1,2,4-triazole as an oil.  The oil was added to 75 ml of concentrated sulfuric acid.  The mixture was worked up in the manner described in Example 2.  8-Chloro-3-methylthio-1 1H-s-triazole [3,4-b] - [3] benzazepine was obtained in the form of crystals.  Recrystallization from methanol gave colorless needles melting at 167-1680C.  The infrared spectrum was identical to the spectrum of the product produced according to Example 6. 



   Example 10
In the manner described in Example 2, 4 - (2,2-diethoxyethyl) -3- (4-methylbenzyl) -5-methylthio-4H- -1,2,4-triazole was obtained in the manner described in Reference Example 19 8-methyl-3-methylthio-l 1H- -s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals.  Recrystallization from ethyl acetate gave colorless needles melting at 161-1 620C.    



  Elemental analysis for: C, 3HI3N3S calculated: C 64.17 H 5.39 N 17.27 found: C 63.92 H 5.33 N 17.32
Example 11
In the manner described in Example 4, 4- (2,2-diethoxyethyl) -3- (4-methoxybenzyl) -5-methylthio-4H-1, 2,4-triazole 8-methoxy-3- methylthio-11H-s-triazole [3,4-b] [3] benzazepine obtained in the form of crystals.  Recrystallization from ethyl acetate gave colorless needles with a melting point of 167-168 "C.    



  Elemental analysis for: Cl3H, 3N3OS calculated: C 60.21 H 5.05 N 16.21 found: C 60.08 H 4.91 N 15.87
Example 12
In the manner described in Example 4, 4- (2,2-diethoxyethyl) -3- (3-methoxybenzyl) -5-methylthio-4H-1,2,4-triazole made from 4- (2,2-diethoxyethyl) -3-methyl-9-methoxy3-methyl was prepared according to Example 25 -thio-ll Hs-triazole [3,4-b] [3] benzazepine obtained in the form of crystals.  Recrystallization from ethyl acetate gave colorless prisms melting at 138-1390C. 

 

  Elemental analysis for: C, 3H, 3N30S calculated: C 60.21 H 5.05 N 16.21 found: C 60.09 H 5.01 N 16.26
Example 13
4.6 g of 3-methylthio-1 lH-s -triazole [3,4-b] [3] benzazepine and 6.7 g of selenium dioxide were added to 100 ml of dioxane. 



  The mixture was heated to reflux with stirring for 7.5 hours.  The insoluble matter was filtered off hot and the filtrate was concentrated.  The crystals thus obtained were filtered off, washed with ethanol and dried, whereby 3-methylthio-1 1H-s-triazole [3,4-b] [3] - benzazepin-1 1-one was obtained in the form of crystals. 



  Recrystallization from methanol gave pale yellow platelets melting at 162-1630C.    



     Elemental analysis for: Cl2H9N3OS calculated: C 59.24 H 3.72 N 17.27 found: C 59.20 H 3.61 N 17.17
Example 14
In the manner described in Example 13, 8-chloro-3-methylthio-IIH-s was reacted with 8-chloro-5-methylthio-1 lH-s-triazole [3,4-b] - [3] benzazepine with selenium dioxide - -Triazol [3,4-b] [3] benzazepin-1 1-one obtained in the form of crystals.  Recrystallization from chloroform-methanol gave colorless platelets with a melting point of 254-2550C. 



     Elemental analysis for: Cl2H8CIN3OS calculated: C 51.89 H 2.90 N 15.13 found: C 51.79 H 2.78 N 15.06
Example 15
In the manner described in Example 13, 8-methyl-3-methylthio-1 1H- -s was reacted with 8-methyl-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine with selenium dioxide -triazol [3,4-b] [3] benzazepin-11-one in the form of crystals.  Recrystallization from methanol gave colorless platelets melting at 178-1 790C.    



  Elemental analysis for: Cl3Hl, NsOS calculated: C 60.68 H 4.31 N 16.33 found: C 60.53 H 4.49 N 16.30
Example 16
To 4.6 g of 3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine in 60 ml of tetrahydrofuran were added 2.4 g of paraformaldehyde together with 4.0 ml of a 40% solution of trimethylbenzylammonium hydroxide in methanol given.  The mixture was refluxed for 30 minutes after which the solvent was evaporated.  The residue was diluted with water and extracted with ethyl acetate.  The ethyl acetate layer was washed with water and dried over Na2SO4.  The solvent was then evaporated.  The crystals were filtered off, washed with isopropyl alcohol and dried.  Here, 1 1-methylene-3-methylthio-1 1H-s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals. 

  Recrystallization from ethyl acetate gave colorless needles melting at 121-1220C. 



  Elemental analysis for: C13H11N3S calculated: C 64.70 H 4.59 N 17.42 found: C 64.79 H 4.52 N 17.34
Example 17
A solution of 4.6 g of 3-methylthio-IIH-s-triazole [3,4-b] - [3] benzazepine in 100 ml of dichloromethane was stirred with ice while cooling, and 5.2 g of m-chloroperbenzoic acid were added.  The mixture was stirred for an additional 40 minutes and then washed with sodium sulfite solution, saturated sodium hydrogen carbonate solution and water in that order and then dried over Na2SO4.  The solvent was then evaporated and the crystalline residue was filtered off and washed with ethyl ether.  Here, 3-methylsulfinyl-1 1H-s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals.  Recrystallization from methanol gave colorless needles melting at 176-1770C. 



  Elemental analysis for: C12H11N3OS calculated: C 58.75 H 4.52 N 17.13 found: C 58.66 H 4.40 N 16.91
Example 18
In the manner described in Example 17, 8-methyl-3-methylthio-11 Hs-triazole [3,4-b] [3] benzazepine was reacted with m-chloroperbenzoic acid, 8-methyl-3-methylsulfinyl-1 1H- s-triazole [3,4-b] [3] benzazepine was obtained.  Recrystallization from methanol gave colorless needles melting at 158-159 C. 



  Elemental analysis for: C, 3H, 3N30S calculated: C 60.21 H 5.05 N 16.21 found: C 60.24 H 4.96 N 15.88
Example 19
In the manner described in Example 17, 8-chloro-3-methylthio-1 1H-s-triazole [3,4-b] [3] benzazepine was reacted with m-chloroperbenzoic acid, 8-chloro-3-methyl sulfinyl-1 1H-s-triazole [3, 4-b] [3] benzazepine was obtained. 



  Recrystallization from methanol gave colorless needles with a melting point of 183-1850C. 



  Elemental analysis for: Cl2HloCIN3OS calculated: C 51.52 H 3.60 N 15.02 found: C 51.41 H 3.43 N 15.19
Example 20
In the manner described in Example 17, 8-methoxy-3-methylthio-1 1H-s-triazole [3,4-b] [3] benzazepine was reacted with m-chloroperbenzoic acid, 8-methoxy-3-methylsulfinyl-11H- s-triazole [3,4-b] [3] benzazepine was obtained.  Recrystallization from chloroform-methanol gave colorless needles with a melting point of 241-242 C. 



  Elemental analysis for: Cl3Hl3N302S calculated: C 56.71 H 4.76 N 15.26 found: C 56.51 H 4.71 N 15.31
Example 21
In the manner described in Example 17, 9 methoxy-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine was reacted with m-chloroperbenzoic acid, 9-methoxy-3-methylsulfinyl-1 1H-s -triazole [3,4-b] [3] benzazepine was obtained.  Recrystallization from methanol gave colorless needles melting at 176-1770C. 



  Elemental analysis for: Cl3H, 3N302S calculated: C 56.71 H 4.76 N 15.26 found: C 56.37 H 4.62 N 15.17
Example 22
In the manner described in Example 17, 3-ethylthio-11H-triazole [3,4-b] [3] benzazepine was reacted with m-chloroperbenzoic acid, 3-ethylsulfinyl-11H-s-triazole [3,4-b] [ 3] benzazepine was obtained.  Recrystallization from ethyl acetate gave colorless needles melting at 9899 C. 



  Elemental analysis for: Cl3H, 3N3OS calculated: C 60.21 H 5. 05 N 16.21 found: C 59.92 H 4.98 N 16.17
Example 23
While cooling with ice, 0.515 g of m -chloroperbenzoic acid was added to 0.23 g of 3-methylthio-IIH-s-triazole- [3,4-b] [3] benzazepine in 5 ml of dichloromethane.  After 5 minutes the ice bath was removed.  The mixture was then left to stand at room temperature overnight.  The reaction mixture was washed with sodium sulfite solution, aqueous sodium hydrogen carbonate solution and water in that order and then dried over Na2SO4.  The solvent was evaporated and the residue treated with ethanol.  Here, 3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals. 



  Recrystallization from ethanol gave colorless needles melting at 110-11 10C.      



  Elemental analysis for: C, 2H "N302S calculated: C 55.16 H 4.24 N 16.08 found: C 54.88 H 4.16 N 16.06
Example 24
0.2 ml of concentrated sulfuric acid and 0.5 ml of 30% hydrogen peroxide were added to a solution of 0.23 g of 3-methylthio-1 lH-s-triazole- [3,4-b] [3] benzazepine in 2 ml of acetic acid added dropwise with stirring.  After 20 hours, sodium sulfite solution was added and the solvent was evaporated.  Saturated aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with chloroform.  The chloroform layer was washed with water and dried over Na2SO4.  The solvent was then evaporated and the residue treated with ethanol. 

  This gave 3-methylsulfonyl-1H-s-triazole [3,4-b] [3] benzazepine in the form of crystals of melting point 110-11 10C.  Because of the infrared spectrum and other key figures, this compound was identical to the compound prepared according to Example 23. 



   Example 25
5.0 ml of concentrated sulfuric acid were added to a solution of 6.1 g of 8-methyl-3-methylthio-IIH -s-triazole [3,4-b] [3] benzazepine in 75 ml of acetic acid.  While cooling and stirring with ice, 12.5 ml of 30% H202 was added dropwise.  The mixture was stirred at room temperature for 10 minutes and then kept on the water bath at 60-65 ° C. for 2 hours.  The mixture was cooled with ice and then aqueous sodium sulfite solution was added to decompose the excess hydrogen peroxide.  The solvent was evaporated.  After adding water, the residue was neutralized with concentrated aqueous ammonia while cooling with ice and extracted with chloroform.  The chloroform layer was washed with water and dried over Na2SO4. 

  The solvent was evaporated and the residue treated with ether.  8-Methyl-3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals.  Recrystallization from ethanol gave colorless needles melting at 152-1530C. 



  Elemental analysis for: Cl3Hl3N302S calculated: C 56.71 H 4.76 N 15.26 found: C 56.67 H 4.71 N 15.42
Example 26
In the manner described in Example 25, by oxidation of 8-chloro-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine with aqueous 30% H202, 8-chloro-3-methylsulfonyl-11H -s-triazole [3,4-b] [3] benzazepine obtained in the form of a crystalline product.  Recrystallization from chloroform-methanol gave colorless prisms with a melting point of 221-2230C.    



  Elemental analysis for: C12H10ClN3O2S calculated: C 48.73 H 3.41 N 14.11 found: C 48.61 H 3.37 N 14.21
Example 27
In the manner described in Example 25, 8-methoxy-3-methylthio-11 Hs-triazole [3,4-b] [3] benzazepine was reacted with 30% aqueous H202, with 8-methoxy -3-methylsulfonyl-11H- s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals.  Recrystallization from methanol gave colorless prisms with a melting point of 145-146 "C.    



     Elemental analysis for: C13H13N3O3S calculated: C 53.59 H 4.50 N 14.42 found: C 53.61 H 4.41 N 14.59
Example 28
In the manner described in Example 25, 9-methoxy-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine was reacted with 30% hydrogen peroxide, 9-methoxy -3-methylsulfonyl-11 Hs -triazol [3, 4-b] [3] benzazepine in the form of crystals.  Recrystallization from ethyl acetate gave colorless prisms with a melting point of 146 to 147 C. 



  Elemental analysis for: C13H13N3O2S calculated: C 53.59 H 4.50 N 14.42 found: C 53.42 H 4.41 N 14.42
Example 29
In the manner described in Example 24, 3-methylthio-11-phenyl-11H-s-triazole [3,4-b] [3] benzazepine was reacted with aqueous 30% H302 to react 3-methylsulfonyl-11-phenyl- 1 Hs-triazole [3,4-b] [3] benzazepine obtained in the form of crystals.  Recrystallization from methanol gave colorless needles melting at 175-1760C. 



  Elemental analysis for: Cl8HlsN3o2s calculated: C 64.07 H 4.48 N 12.46 found: C 63.93 H 4.47 N 12.58
Example 30
In the manner described in Example 24, 1 1-methyl-3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine was reacted with 30% aqueous H2O2 solution, 11 -Me- thyl-3-methylsulfonyl-11 Hs-triazole [3,4-b] [3] benzazepine in
Form of crystals was obtained.  Recrystallization from ethanol gave colorless prisms with melting point 147
1480C. 



  Elemental analysis for: C13H13NsO2S calculated: C 56.71 H 4.76 N 15.26 found: C 56.49 H 4.61 N 15.22
Example 31
While cooling with ice and stirring, 0.224 g of chloroperbenzoic acid was added to a solution of 0.243 g of 3-methylthio-1 lH-s-triazole [3,4-b] [3] benzazepine in 4 ml of dichloromethane.  The mixture was stirred for 30 minutes and then another 0.035 g of m-chloroperbenzoic acid was added.  After further stirring for 1 hour, the reaction mixture was washed with aqueous sodium sulfite solution u.  saturated aqueous sodium bicarbonate solution shaken well. 



  The dichloromethane layer was washed with water and dried over Na2SO4.  The solvent was evaporated and the crystalline precipitate was filtered off and washed with ethyl acetate.  Here, 3-methylsulfinyl-1 1H-s-triazole [3,4-b] [3] benzazepin-11-one was obtained in the form of crystals.  Recrystallization from chloroform-methanol gave colorless needles melting at 208-21 10C.    

 

  Elemental analysis for: C12H0N3O2S calculated: C 55.58 H 3.50 N 16.21 found: C 55.82 H 3.34 N 16.17
Example 32
In the manner described in Example 17, 1 1-methylene-3-methylthio-1 1H-s-triazole [3, 4-b] [3] benzazepine was reacted with m-chloroperbenzoic acid, 11-methylene-3- - methylsulfinyl-11 Hs-triazole [3, 4-b] [3] benzazepine was obtained in the form of crystals.  Recrystallization from ethyl acetate gave colorless prisms with a melting point of 140-142 "C.    



  Elemental analysis for: C13H11N3OS calculated: C 60.68 H 4.31 N 16 33 found: C 60.79 H 4.27 N 16.26
Example 33
0.2 ml of concentrated sulfuric acid was added to 0.230 g of 3-methylthio-11H-s-triazole [3,4-b] [3] benzazepine in 3 ml of acetic acid, followed by 0.3 ml of 30% aqueous hydrogen peroxide solution while cooling with ice were added dropwise.  The mixture was allowed to stand at 3 to 5 C for 7 hours.  After this time, aqueous sodium sulfite solution was added to the mixture to decompose excess hydrogen peroxide.  The solvent was evaporated and the residue diluted with water.  The crystals were filtered off.  Here, 3-methylsulfinyl -1 1H-s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals. 

  Recrystallization from methanol gave colorless needles with a melting point of 176-177 "C.     Based on the infrared spectrum and other key figures, this compound was identified as the compound prepared according to Example 17. 



   Example 34
To 0.522 g of 3-methylsulfonyl-1 1H-s-triazole [3,4-b] [3] - -benzazepine in 5 ml of methanol was added 3 ml of 2N sodium methoxide / methanol.  The mixture was refluxed for 15 minutes after which the solvent was evaporated.  The residue was diluted with water and extracted with chloroform.  The chloroform layer was washed with water and dried over Na2SO4.  The solvent was then evaporated and the residue treated with isopropyl ether.  Here, 3-methoxy-11H- -s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals.  Recrystallization from ethyl acetate-n-hexane gave colorless prisms with a melting point of 160-1610C.    



     Elemental analysis for: C12HuN3O calculated: C 67.59 H 5.20 N 19.71 found: C 67.31 H 5.15 N 19.72
Example 35
In the manner described in Example 34, 3-methyl sulfonyl-1 1 Hs-triazole [3,4-b] [3] benzazepine was reacted with sodium ethoxide / ethanol instead of sodium methoxide / methanol, 3-ethoxy-1 H-s -triazol [3,4-b] [3] benz-azepine was obtained in the form of crystals.  Recrystallization from acetone gave colorless needles melting at 143-144 C. 



  Elemental analysis for: Cl3Hl3N3O calculated: C 68.70 H 5.77 N 18.49 found: C 68.47 H 5.68 N 18.33
Example 36
In the manner described in Example 35, 0.245 g of 3-methylsulfinyl-1 1H-s-triazole [3,4-b] [3] benzazepine instead of 3-methylsulfonyl-11H-s-triazole [3,4-b] [3] benzazepine reacted with 1.2 ml of in-sodium ethoxide / ethanol in 2 ml of ethanol, whereby 3-ethoxy-II Hs-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals.  Recrystallization from acetone gave colorless needles melting at 143-144 C. 



  The infrared spectrum of this product matched the spectrum of the compounds prepared according to Example 35. 



   Example 37
1.0 ml of 2N sodium methoxide / methanol was added to a solution of 0.262 g of 3-bromo-1 IH-s-triazole [3,4-b] [3] benzazepine in 2 ml of methanol.  The mixture was refluxed for 1 hour.  The solvent was evaporated.  After adding water, the residue was extracted with ethyl acetate.  The ethyl acetate layer was washed with water and dried over Na2SO4.  The solvent was then evaporated and the residue treated with isopropyl ether.  Here, 3-methoxy-11 H-s-triazole [3,4-b] [3] benzazepine was obtained in the form of crystals.  Recrystallization from ethyl acetate-n-hexane gave colorless prisms with a melting point of 161-162 C.     The infrared spectrum of this product was identical to the spectrum of the compound prepared according to Example 34. 



   Example 38
According to the methods described in the preceding examples or  In analogous processes, the compounds mentioned below were prepared from the corresponding starting compounds. 



   By reacting 8-methyl-3-methylsulfonyl-IIH- -s-triazole [3,4-b] [3] benzazepine with sodium methoxide, 3-methoxy-8-methyl-1 1H-s-triazole [3,4- b] [3] benzazepine in the form of colorless prisms (after recrystallization from ethyl acetate) obtained with a melting point of 148-1490C. 



   By reacting 8-chloro-3-methylsulfonyl-1 1H-s-triazole [3,4-b] [3] benzazepine with sodium methoxide, 8-chloro-3-methoxy-1 1H-s-triazole [3, 4 -b] [3] benzazepine in the form of colorless needles (after recrystallization from aqueous acetone) with a melting point of 177-1780C. 



   By reacting 8-methoxy-3-methylsulfonyl-1 1H- -s-triazole [3,4-bj [3] benzazepine with sodium methoxide, 3,8-dimethoxy-11H-s-triazole [3,4-b] [ 3] received benzazepine. 



  Colorless needles (after recrystallization from aqueous methanol) with a melting point of 185-1860C. 



   By reacting 9-methoxy-3-methylsulfonyl-1 1H- -s-triazole [3,4-b] [3] benzazepine with sodium methoxide, 3,9-dimethoxy-1 1H-s-triazole [3,4b] [ 3] received benzazepine. 



  Colorless needles (after recrystallization from aqueous acetone) with a melting point of 176-177 "C.    



   By reacting 3-methylsulfonyl-11-phenyl-IIH- -s-triazole [3,4-b] [3] benzazepine with sodium methoxide, 3-methoxy-1 1-phenyl-1 1H-s-triazole [3,4 -b] t3] benzazepine obtained.  Colorless prisms (after recrystallization from aqueous methanol) with a melting point of 183-184 C. 



   By reacting 1 1-methyl-3-methylsulfonyl-1 1H- -s-triazole [3,4-b] t3] benzazepine with sodium methoxide, 3-methoxy-1 1-methyl-11 Hs-triazole [3,2- b] t3] benzazePin obtained.  Colorless prisms (after recrystallization from ether) with a melting point of 101-102 C.    



   By reacting 3-bromo-1 lH-s-triazole [3,4-b] [3] - benzazepine with sodium ethoxide, 3-ethoxy-1 1H-s-triazole [3,4-b] [3] received benzazepine.  Colorless needles (after recrystallization from acetone) with melting point 143-1440C. 

 

  The infrared spectrum of this compound was identical to the spectrum of the products obtained according to Examples 35 and 36. 



   By reacting 11-methylene-3-methylsulfinyl-11H-s-triazole [3,4-b] [3] benzazepine with sodium methoxide, 3-methoxy-11-methylene-11H-s-triazole [3,4-b ] [3] received benzazepine.  Colorless needles (after recrystallization from ethyl acetate) with a melting point of 160-1610C. 

 

   By reacting 3-methylsulfinyl-1 1H-s-triazole [3,4-b] [3] benzazepin-1 1-one with sodium methoxide, 3-methoxy-11H-s-triazole [3,4-b] [3 ] benzazepin-11-one obtained.  Colorless platelets (after recrystallization from methanol) with a melting point of 149-1500C.   



   Example 39
Preparation of tablets for use as an analgesic 1) 3-methylthio-11 Hs-triazole [3,4-b] [3] - -benzazepine 10 mg 2) lactose 55 mg 3) corn starch 34.5 mg 4) magnesium stearate 0, 5 mg
100.0 mg per tablet Manufacture:
22.5 mg of corn starch are mixed with ingredients (1) and (2).  The mixture is granulated with a paste made from 7 mg of corn starch.  Ingredient (4) and 5 mg corn starch are added to the granules.  The mass is pressed into tablets with a diameter of 7 mm.  


    

Claims (8)

 PATENT ADDRESS 1. Compounds of the formula: EMI1.1  in which R1 and R2 are hydrogen or alkyl, X for EMI1.2  wherein R3 and R4 are hydrogen, alkyl, aryl or aralkyl and R5 is hydrogen or alxyl, Z is -SR6, -S (O), R6 or, OR7, wherein R6 and R7 are alkyl or aralkyl and n is 1 or 2 , is and the ring A is unsubstituted or mono- or polysubstituted with halogen, lower alkyl, lower alkoxy or trifluoromethyl, and their salts.  2. Pharmaceutical preparations containing as an active ingredient at least one compound according to claim 1 and a pharmaceutically acceptable carrier.  3. Process for the preparation of compounds of the formula: EMI1.3  in which R1 and R2 are hydrogen or alkyl radicals and R3 and R4 are hydrogen, alkyl radicals, aryl radicals or aralkyl radicals, Ro is an alkyl radical or aralkyl radical and ring A is unsubstituted or mono- or polysubstituted by halogen atoms, lower alkyl radicals, lower alkoxy radicals and / or trifluoromethyl radicals , characterized in that compounds of the formula: EMI1.4  in which Q is carbonyl or carbonyl protected by an acetal group and the other symbols have the meanings given above, subject to intramolecular cyclization.  4. Process for the preparation of compounds of the formula: EMI1.5  in which Rt, R2, R3, R4 and Ro have the meanings given in claim 3 and ring A is unsubstituted or substituted in the manner mentioned in claim 3, characterized in that compounds of the formula: EMI1.6  in which R1, R2, R3, R4 and A have the meanings given above, with an alkylating agent or aralkylating agent.  5. Process for the preparation of compounds of the formula: EMI1.7  in which R1 and R2 are hydrogen or alkyl, X for EMI 1.8  wherein R3 and R4 are hydrogen, alkyl, aryl or aralkyl and Rs is hydrogen or alkyl, Rs is alkyl or aralkyl n is 1 or 2 and ring A is unsubstituted or simple or with halogen atoms, lower alkyl radicals, lower alkoxy radicals and / or trifluoromethyl radicals is multiply substituted, characterized in that compounds of the formula: EMI1.9  in which all symbols have the meanings given above, oxidized.  6. Process for the preparation of compounds of the formula: EMI2.1  in which R1 and R2 are hydrogen or alkyl radicals, X for EMI2.2  wherein R3 and R4 are hydrogen, alkyl radicals, aryl radicals or aralkyl radicals and R5 is hydrogen or an alkyl radical, and R7 is an alkyl radical or aralkyl radical and ring A is unsubstituted or mono- or polysubstituted by halogen atoms, lower alkyl radicals, lower alkoxy radicals and / or trifluoromethyl radicals is characterized in that compounds of the formula: EMI2.3  in which Y is a halogen atom or a group of the formula -S (O) nR5, in which R6 is an alkyl radical or aralkyl radical and n is 1 or 2, and the other symbols have the meanings given above, with an alcoholate of the formula: : R7-OM, (VI) in which M is an alkali metal and R? has the meaning given above.  7. Process for the preparation of compounds of the formula: EMI2.4  in which Rl, R2 and R6 have the meanings given in claim 3 and the ring is unsubstituted or substituted in the manner mentioned in claim 3, characterized in that compounds of the formula Ia in which R3 and R4 are hydrogen, using a Oxidizing agent oxidized.  8. Process for the preparation of compounds of the formula: EMI2.5  in which R1, R2 and R6 have the meanings given in Claim 3, R5 represents hydrogen or alkyl and ring A is unsubstituted or substituted in the manner mentioned in Claim 3, characterized in that compounds of the formula Ia in which R3 and R4 are hydrogen, with an aldehyde of the formula RtCHO, in which R5 has the meaning given above.  The invention relates to new, valuable triazolbenzazepine derivatives.  From U.S. Patent No. 4,002,638 to Y. Kuwada et al are benzazepine derivatives of the formula: EMI2.6  wherein the ring A is unsubstituted or substituted by halogen, nitro, alkyl, alkoxy or trifluoromethyl, R is hydrogen or optionally substituted alkyl, X is oxygen or sulfur and Y is -CHfCH2- or CH = CH-, and their pharmaceutically acceptable salts known. These compounds have pharmacological effects such as analgesic and muscle relaxant effects.    New triazolbenzazepine derivatives of the formula: EMI2.7  in which R1 and R2 are hydrogen or alkyl, X for EMI 2.8  wherein R3 and R4 are hydrogen, alkyl, aryl or aralkyl and R5 is hydrogen or alkyl, Z is -SR6, -S (O) "R6 or -OR7, wherein R6 and R7 are alkyl or aralkyl and n is 1 or 2 , is and the ring A is unsubstituted or mono- or polysubstituted with halogen, lower alkyl, lower alkoxy or trifluoromethyl, and their salts, which are effective and valuable as medicaments, for example as muscle relaxants, analgesics and anti-inflammatory agents. ** WARNING ** End of CLMS field could overlap beginning of DESC **.