CH451179A - Process for the production of new ketones of the lysergic acid series - Google Patents

Description

  

  
 



  Process for the production of new ketones of the lysergic acid series
It has been found that new ketones of the lysergic acid series of the general formula I (see formula sheet), in which Rt is hydrogen, an alkyl group with 1-5 carbon atoms or an aralkyl group with 7-9 carbon atoms and R2 is a monocyclic optionally substituted by alkyl or alkoxy groups Mean aryl group and xy for the grouping
EMI1.1
 can be obtained by adding compounds of the general formula II in which R1 and xy have the above meanings and;

   R3 and R4 denote hydrogen, or an alkyl group with 1-5 carbon atoms, or together with the nitrogen atom form a pyrrolidine, piperidxine or morphine ring, with organometallic compounds of the general formula III, in which R2 has the above meaning and Me is lithium or a halogenomagnesium radical, wherein halogen represents chlorine, bromine or iodine, means, reacts and hydrolyzes the complex obtained.



   As compounds of the general formula III Eigmel III, in which R2 has the above meaning and Me is lithium or a halogenated magnesium radical, in which Haloz. B. phenyl magnesium bromide.



   The method is carried out, for example, as follows: The solution of a lysergic acid derivative of the general formula II in an inert organic solvent, such as. B.



  Benzene or ether, with a solution of a compound of the general formula III in the same or in a different organic solvent (e.g. ether or tetrahydrofuran) and the mixture is left to stand for a while at room temperature. It is then decomposed with water and the organic layer is separated off. After drying the organic phase with sodium sulfate or potash, the solvent is evaporated off and the residue is purified by known methods by crystallization and chromatography on aluminum oxide. The new ketones of the lysergic acid series produced by the present process are usually easily crystallizing substances at room temperature and form salts with inorganic or organic acids.



   With Keller's color reagent (glacial acetic acid containing iron (III) chloride and conc. Sulfuric acid) they give a characteristic color depending on the type of substituent Rt.



   The new ketones of the lysergic acid series obtained according to the invention have a sedative effect on motor and psychological functions and influence the tone of the vessels.



   The invention also includes the preparation of salts of the new compounds. Such salts are e.g. B. those with inorganic acids such as hydrochloric acid, hydrobromic acid or sulfuric acid, or with organic acids such as fumaric acid, maleic acid, tartaric acid, methanesulfonic acid etc.



   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. As auxiliary substances are used, for. B. for tablets and dragees: lactose, starch, talc,
Stearic acid etc. for syrups: cane sugar, invert sugar,
Glucose solutions and the like a. for injection preparations: water, alcohols, glycerine, vegetable oils and the like. for suppositories: natural or hardened oils and waxes etc. a. 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 scope of the invention in any way, all temperatures are given in degrees Celsius. The melting points are uncorrected.
EMI2.1




   example
6-methyl-8-benzoyl-ergoline A solution of 0.2 g of 9, 1O-dihydroI-lysergic acid piperidide in 50 ccm of boiling benzene is mixed with 2 cc of a freshly prepared ethereal Li-phenyl solution, of which 1 com 2, 9 ccm of 0.2 N HCl consumed on methyl red, added, a white gelatinous precipitate separating out. After standing for 1 1/2 hours at room temperature, it is shaken out between sodium hydroxide solution and chloroform. The organic phase is dried over sodium sulfate, the solvent is evaporated off and the residue is chromatographed on a column of 20 g of aluminum oxide, the 6-methyl-8-benzoyl-ergoline being washed into the filtrate with absolute chloroform.

   The 6-methyl-8-benzoylergoline crystallizes from acetone in boat-shaped leaves with a melting point of 220-2210. [a] D20 = 1200 (c = 0.5 in pyridine).



   Keller's color reaction: violet-tinged blue.

 

Claims (1)

PATENT CLAIM Process for the preparation of new ketones of the lysergic acid series of the general formula I, in which R1 is hydrogen, an alkyl group with 1-5 carbon atoms or an aralkyl group with 7-9 carbon atoms and R2 is a monocyclic aryl group optionally substituted by alkyl or alkoxy groups and xy is the grouping EMI2.2 is characterized in that compounds of the general formula II, in which Rt and xy have the above meaning and R3 and R4 are hydrogen or an alkyl group with 1-5 carbon atoms, or together with the nitrogen atom form a pyrrolidine, piperidine or morpholine ring, with organometallic compounds of the general formula III, in which R2 is as defined above and Me is lithium or a halogenomagnesium radical, in which halogen is chlorine, bromine or iodine, and the complex is hydrolyzed.