CH493521A - (A) Compds. (I):- where R1 = H or Me; R2 = 7-9 C aralkyl or aryl (opt. substd. by one or more methyl or 1-4 C alkoxy groups, Br or Cl); X Y = CH - Google Patents

Abstract

(A) Compds. (I):- where R1 = H or Me; R2 = 7-9 C aralkyl or aryl (opt. substd. by one or more methyl or 1-4 C alkoxy groups, Br or Cl); X Y = CH = (B) Acid addition salts of (I). Sedatives and neuroleptics; at high doses, antiserotonin and sympathicomimetic effects. 10 ml. N-phenylpiperazine added to 5 g. d-lysergic acid chloride hydrochloride in 200 ml. CH2Cl2 at 0 deg.C., the mixt. stirred 1 hr. at room temp., extd. between a soln. of Na2CO3 and CHCl3, the org. extd. dried, evapd., the residue mixed with Et2O and the insol. residue chromatographed on 240 g. SiO2 gel gave on elution with CHCl3 contng. 1.5-2.0% MeOH (I, R1 = H, R2 = Ph, X Y = CH = ), bimaleate m. 200 deg.C., (alpha)20D -20 deg. (C = 0.5, 50% alc.).

Description

  

  
 



  Process for the preparation of new heterocyclic compounds
The present invention relates to a process for the preparation of compounds of the general formula I in which R1 is hydrogen or methyl and R2 is aralkyl with 7-9 carbon atoms or aryl, the aryl radical in each case being replaced by one or more of the following groups, methyl, alkoxy may be substituted with 1-4 carbon atoms, chlorine or bromine, and their acid addition salts.



   According to the invention, the compounds of general formula I and their acid addition salts are obtained by catalytically hydrogenating the compounds of general formula II in which R1 and R2 have the above meaning, isolating the compounds of formula I obtained in a manner known per se and optionally subsequently converting them into them Acid addition salts transferred.



   This hydrogenation is preferably carried out at room temperature and normal pressure and using catalysts such as palladium deposited on aluminum oxide or activated carbon, in an organic solvent inert under the reaction conditions, such as ethyl acetate, methanol, ethanol or mixtures of methylene chloride with methanol or ethanol.



  After the hydrogen uptake has ended (approx. 2 hours), the catalyst is filtered off and the solvent, respectively. The solvent mixture is removed and the residue is purified in a manner known per se, such as by crystallization and / or chromatography.



   The compounds of general formula I prepared according to the invention are solid compounds which usually crystallize nicely at room temperature and which, with suitable organic or inorganic acids, form stable, crystallized, more or less readily water-soluble salts. Such salts are, for example, the hydrochlorides, hydrobromides, sulfates, phosphates, fumarates, maleinates, malates, acetates or tartrates. With Keller's and van Urk's color reagents, the compounds prepared according to the invention give characteristic colorations.



   The compounds of general formula I prepared according to the invention have sedative-neuroleptic properties which make their use in the treatment of neurovegetative disorders and in psychiatry
2 Make possible the treatment of states of mental excitement and anxiety, as they occur in neuroses and psychoses. In high doses they also have a sympathomimetic and serotonin-antagonistic effect.



   The new compounds can be used as medicaments alone or in corresponding medicament forms for enteral or parenteral administration.



  In order to produce suitable dosage forms, these are processed with inorganic or organic, pharmacologically indifferent auxiliaries. The auxiliaries used are e.g.



  for tablets and dragees:
Lactose, starch, talc, stearic acid, etc.



  for syrups:
Cane sugar, invert sugar, glucose solutions, etc.



  for injection preparations:
Water alcohols, glycerine, vegetable oils and the like.



  for suppositories:
Natural or hardened oils and waxes, etc. more.



   In addition, the preparations can contain suitable preservatives, stabilizers, wetting agents, solubilizers, sweeteners, colorants, flavorings, etc.



   In the following example, which explains the implementation of the method but is not intended to limit the invention in any way, all temperatures are given in degrees Celsius and have been corrected.
EMI1.1
  
EMI2.1


 

   example
9,10-dihydro-d-lysergic acid-N-phenylpiperazide
36 g of d-lysergic acid-N-phenylpiperazide are dissolved in 750 ml of an ethanol / methylene chloride (1: 1) mixture and hydrogenated in the presence of 25 g of a prehydrogenated palladium-aluminum oxide catalyst at room temperature and normal pressure. After the uptake of hydrogen has ceased (approx. 2 hours), the catalyst is filtered off and the methylene chloride is removed in a rotary evaporator in vacuo, with crystallization starting to 2630 (dec.), [cc] D20 = -82.50 (c = 2 in methylene chloride / methanol 1: 1).

 

Claims (1)

PATENT CLAIM Process for the preparation of compounds of the general formula I, wherein; R1 represents hydrogen or methyl and R2 represents aralkyl with 7-9 carbon atoms or aryl, where the aryl radical can in each case be substituted by one or more of the following groups, methyl, alkoxy with 1-4 carbon atoms, chlorine or bromine, and their acid addition salts , characterized in that compounds of the general formula II, in which R1 and R have the above meanings, are catalytically hydrogenated, the compounds of the formula I obtained are isolated and, if appropriate, then converted into their acid addition salts. SUBClaim Process according to claim, characterized in that the hydrogenation is carried out in an organic solvent which is inert under the reaction conditions at room temperature and normal pressure in the presence of a palladium catalyst.