AT219610B - Process for the preparation of new iminodibenzyl derivatives and their salts - Google Patents

Description

  

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  Process for the preparation of new iminodibenzyl derivatives and their salts
The present invention relates to a process for the preparation of new N-heterocyclic compounds with valuable pharmacological properties, as well as the associated intermediate products.



   It has been found that compounds with valuable pharmacological properties which correspond to the general formula I
 EMI1.1
 where R is hydrogen, a lower alkyl radical or an aralkyl radical, X is a straight-chain or branched alkylene radical with 2 - 6 carbon atoms, and Am is a lower alkylamino or dialkylamino group, one of the two alkyl radicals of a dialkylamino group Am being directly (1) with the alkyl radical Xor both alkyl radicals can be linked directly (2) or via an oxygen atom (3), a lower alkylimino (4), hydroxyalkylimino (5) or alkanoyloxyalkylimino group (6) or can produce their salts with inorganic or organic acids by one compounds of the general formula:

   
 EMI1.2
 where X 'and Am "' denote radicals which, with the radicals X and Am defined above, except for at least one carbonyl group bonded to a nitrogen atom which takes the place of a methylene group in at least one of the radicals X 'and Am"', match, and R 'has the meaning given under the general formula 11, reduced with an alkali metal-earth metal hydride, in particular with lithium aluminum hydride and, if necessary, the reduction product, depending on the meaning of R', preferably by acid hydrolysis or by hydrogenolysis into a compound of the general formula I defined above.



   The following formulas are specific examples to illustrate the above-mentioned six bonding possibilities in the grouping X - Am

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 EMI2.1
 
 EMI2.2
 
 EMI2.3
 
 EMI2.4
 

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 EMI3.1
 derworin R 'and X have the meaning given above with alkali metal compounds of lower alkanecarboxamides, alkanecarboxylic acid N-alyl amides, dialkanecarboximides, 6-valerolactam, e-caprolactam, succinimide or glutarimide,

   or optionally also by acylation of substituted 5-aminoalkyl- or 5-alkylaminoalkyl-iminodibenzyls of the general formula
 EMI3.2
 wherein Am "denotes the amino group or a lower alkylamino group and X and R 'have the meaning given above.



   The compounds which can be prepared according to the invention have, in particular, antiallergic, sedative, serotonin-antagonistic, antipyretic and thymoleptic activity with only low vegetative activity
Side effects. They are suitable, for example, for the treatment of certain forms of mental illness, in particular mood depression, and they can also be used orally or parenterally in the form of aqueous solutions of non-toxic salts. Some of them are also suitable as intermediate products for the manufacture of other substances with similar properties.



   With inorganic or organic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanedisulfonic acid, acetic acid, succinic acid, fumaric acid, maleic acid, malic acid, tartaric acid, citric acid, benzoic acid and phthalic acid, the compounds of the general formula I which can be prepared according to the invention form salts, some of which are water soluble.



   The following examples are intended to explain the preparation according to the invention of compounds of the general formula I in more detail, but by no means represent the only possible embodiments of the same. In the examples, parts mean parts unless otherwise noted. Parts by weight; these are related to parts of volume as g to cms. The temperatures are given in degrees Celsius.



    Example 1: 4.26 parts of 2-benzyloxy-5-piperidino-caxbonylmethyl-iminodibenzylin100 volumetric parts of tetrahydrofuran are added dropwise with stirring to a suspension of 1 part of lithium aluminum hydride in 100 parts by volume of diethyl ether, and the reaction mixture is then heated to reflux for 5 hours cooled and decomposed with water. The ethereal phase is repeated three times with 2-n. Hydrochloric acid extracted, the combined hydrochloric acid extracts with conc. Ammonia solution made basic and the resulting suspension extracted with ether. The ether extract is dried over sodium sulfate and evaporated, the crude 3-benzyloxy-5- (ss-piperidino-ethyl) -iminodibenzyl remaining.

   This is converted into the hydrochloride by means of an ethanolic hydrogen chloride solution and the latter is recrystallized from methanol / acetone. M.p. 208-2090 after conversion into fine needles above 1850.



   Example 2: 4.0 parts of 2, benzyloxy-5- [y- (N-formyl-methylamino) -propylJ-iminodibenzyl in 100 parts by volume of diethyl ether are added dropwise with stirring to a suspension of 1 part of lithium aluminum hydride in 50 parts by volume of diethyl ether and that The reaction mixture was heated to reflux for 5 hours. After cooling, the excess lithium aluminum hydride is decomposed with 3 parts by volume of methanol in 15 parts of ether, water is added to the whole, the ethereal phase is separated off and 2-n. Hydrochloric acid extracted. The combined extracts are with conc. Caustic soda alkaline

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 posed. The precipitated base is taken up in ether, dried and evaporated.

   The residue is distilled in a high vacuum, the 2-benzyloxy-5- (γ-dimethylamino-propyl) -iminodibenzyl passes over under 0.002 mm pressure at 212-215.
 EMI4.1
 (y-dimethylamino-propyl) -iminodibenzyl mp. 132 PATENT CLAIM: Process for the preparation of new iminodibenzyl derivatives of the general formula
 EMI4.2
   where R is hydrogen, a lower alkyl ester or an aralkyl radical, X is a straight-chain or branched alkylene radical having 2 to 6 carbon atoms. and Am is a lower alkylamino or dialkylamino group
 EMI4.3
 ganischen or organic acids, characterized in that one is a compound of the general formula
 EMI4.4
 
 EMI4.5
 

** WARNING ** End of DESC field may overlap beginning of CLMS **.

 

Claims (1)

Reduced on the '"residual metal hydride, in particular with lithium aluminum hydride and, if necessary, the reduction product, depending on the meaning of R', preferably by acid hydrolysis or by hydrogenolysis in a compound of the general formula I defined above and optionally converting the bases obtained with inorganic or organic Acids converted into salts. ** WARNING ** End of CLMS field may overlap beginning of DESC **.