AT217465B - Process for the production of new esters of the indole series - Google Patents

Description

  

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  Process for the preparation of new esters of the indole series It has been found that new esters of the indole series of the general formula I can be:
 EMI1.1
 in which R and R, lower, identical or different alkyl groups with in particular 1-6 carbon atoms and Rs the remainder of an organic carboxylic acid, and their salts with inorganic ones
 EMI1.2
   mel II:
 EMI1.3
 in which R and l) have the above meaning, esterified by treatment with a reactive derivative of an organic carboxylic acid, whereupon the end products can be converted into the corresponding salts with inorganic or organic acids.



   The procedure is carried out as follows, for example:
A hydroxyindole derivative of the above formula II is first dissolved either in the presence of 1 mol of base in water or in the form of its salt with an inorganic base in an inert solvent and the solution is mixed with a suitable acid derivative. Acid halides, in particular acid chlorides such as e.g. Acetyl chloride, benzoyl chloride, p-toluene sulfonic acid chloride, chlorine sulfonic acid and the like. a. ; acetic anhydride can also be used for the acetylation. One sets z. B. 4-hydroxy-N-dimethyl-tryptamine in the form of the alkali salt in an inert solvent such as toluene, l, 2-dimethoxyethane, tert.

   Amyl alcohol, etc., with benzoyl chloride, shake for a few hours at room temperature and then distribute the reaction mixture in a separating funnel between water and a water-immiscible organic solvent. The organic phase is separated off and dried and the solvent is evaporated. The remaining crude product can be obtained directly from a suitable solvent or solvent mixture, such as. B. chloroform or ethyl acetate / petroleum ether etc., are crystallized. If this does not work, filtration through an aluminum oxide column is recommended.

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   The hydroxyindole derivatives of the above formula II used as starting materials are produced according to Belgian patent specification no. 582352.



   The new connections are solid at room temperature, and for the most part beautiful. Crystallized compounds. With organic and inorganic acids, they form stable, sometimes water-soluble salts. They are moderately to well soluble in almost all organic solvents, but are generally sparingly soluble in water. With the Keller reagent (glacial acetic acid containing ferric chloride and concentrated sulfuric acid), they give a positive color reaction, the shade of which depends on the type of ester group.



   The new esters of the indole series are characterized by interesting, therapeutically utilizable pharmacodynamic properties. Many of these stimulate the central sympathetic nervous system in particular, which manifests itself in mydriasis, an increase in blood pressure, an increase in temperature and an increase in blood sugar as well as an inhibition of bowel activity. Furthermore, they have clear serotone-antagonistic properties and promote the spinal reflexes. At the same time, the substances have a slightly calming effect and inhibit drive. They are also able to suppress the sedative and cramp-promoting effects of reserpine.

   As a result of their centrally vegetative and their drive-inhibiting properties as well as their reserpine-antagonistic properties, they can be used for the treatment of a wide variety of mental illnesses, such as obsessive-compulsive disorders and depression, moods and anxiety of neurotic and psychotic origins. The 4-hydroxy-indole - esters of the above formula I show a very low toxicity. They are absorbed practically quantitatively by the organism and are therefore preferably used orally, but can just as easily be administered subcutaneously, intramuscularly or intravenously. They are intended to be used in therapy, but are also valuable intermediates for the manufacture of drugs.



   In the following examples, which illustrate the implementation of the process but are not intended to restrict the scope of the invention in any way, all temperatures are given in degrees Celsius.



  The melting points are uncorrected.



    Example 1: 4-Hydroxy-N-dimethyltryptamine-benzoic acid ester [3- (2'-dimethylaminoethyl) - - 4-benzoxy-indole]. 408 mg of 4-hydroxy-N-dimethyltryptamine are evaporated to dryness with 2 cm of ln sodium hydroxide solution, the dry residue is dissolved in 15 cm! 1, 2-dimethoxy-ethane and mixed with a solution of 267 mg of benzoyl chloride in 5 cms of 1, 2-dimethoxy-ethane. The mixture is shaken on the shaker for two hours and then shaken between water and chloroform in a separating funnel.

   The separated chloroform phase is dried over potash, evaporated to dryness and the residue is crystallized from ethyl acetate / petroleum ether, 4-hydroxy-N-dimethyltryptamine-benzoic acid ester being obtained in hexagonal plates with a melting point of 109-1110.



   Keller's color reaction: brownish violet.



    Example 2: 4-Hydroxy-N-dimethyltryptamine-acetic acid ester [3- (2'-dimethylaminoethyl) -4-acetoxy-indole]. 408 mg of 4-hydroxy-N-dimethyltryptamine are reacted with acetyl chloride as in Example 1 in the form of the sodium salt in 1,2-dimethoxyethane solution and the reaction mixture is worked up as described in Example 1 after standing for two hours. After crystallization from ether / petroleum ether, 4-hydroxy-N-dimethyl-tryptamine-acetic acid ester melts at 92 - 950.



   Keller's color reaction: green, becomes violet.



    Example 3: 4-Hydroxy-N-dimethyltryptamine trimethyl acetic acid ester [3- (2'-dimethylamino-ethyl) -4-trimethylacetoxy-indole]. 345 mg of sodium are dissolved in 30 cm3 of abs. Ethanol, add 2.81 g of 4-hydroxy-N-dimethyltryptamine under a nitrogen atmosphere and then evaporate to dryness. 40 cms of 1,2-dimethoxyethane are added to the dry residue, a solution of 1.69 g of trimethylacetyl chloride (pivalic acid chloride) in 20 ems of 1,2-dimethoxyethane is added and the mixture is stirred for three hours at room temperature.

   The reaction mixture is filtered through talc, the filtrate is evaporated to dryness and the residue is chromatographed on a column of aluminum oxide with chloroform. 4-Hydroxy-N-dimethyltryptamine trimethyl acetic acid ester crystallizes from benzene / petroleum ether in boats and drusen with a melting point of 123-1240.



   Keller's color reaction: green.



   Van Urk's color reaction: light blue.

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

 

Claims (1)

PATENT CLAIMS: 1. Process for the preparation of new esters of the indole series of the general formula I: <Desc / Clms Page number 3> EMI3.1 in which R. and R denote lower, identical or different alkyl groups with in particular 1-6 carbon atoms and R. denotes the remainder of an organic carboxylic acid, and their salts with inorganic or organic acids, characterized in that a hydroxyindole derivative of the general Formula II: EMI3.2 in which R'andR have the above meaning, esterified by treatment with a reactive derivative of an organic carboxylic acid, whereupon the end products can be converted into the corresponding salts with inorganic or organic acids. 2. The method according to claim 1, characterized in that 4-hydroxy-N-dimethyltryptamine of the formula III: EMI3.3 in the form of an alkali salt, in an inert organic solvent, optionally under nitrogen EMI3.4 tryptamine trimethyl acetic acid ester of formula IV: EMI3.5 implements.