DE2344608C3 - Process for the preparation of D-lysergic acid amides - Google Patents

Description

15th

The invention relates to a process for the preparation of D-lysergic acid amides by reacting D-lysergic acid chloride hydrochloride with amino alcohols in the presence of a solvent.

Several processes for the preparation of D-lysergic acid amides are known, the most well known Process is reacted D-Lysergic acid azide with amino alcohols, whereby because of the racemization of the 2; D-Lysergic acid hydrazide the amides can be obtained with low yields. The D-lysergic acid can be reacted with amino alcohols in the presence of trifluoroacetic acid. According to a different procedure the basic salt of lysergic acid is converted into a mixed anhydride with sulfur trioxide which is reacted with various primary or secondary amines and amino alcohols.

The disadvantage of this process is the occurrence of a large number of by-products. J

Likewise, amides are made by reacting D-lysergic acid with amino alcohols in the presence of aromatic or aliphatic carbodiimides produced, but with the disadvantage that strong isomerization takes place during the course of the reaction.

Through the reference Chem. Abstr. 71 (1969), issue 11, Ref. 50 307s a process has become known in which the hydrochloride of Lysergic acid chloride with the Methyl ester of α-aminopropionic acid (which must be prepared beforehand) and the product obtained (Ester of the amide) is reduced with sodium borohydride and the reduction product is then converted into the maleate will. This procedure includes a large number of procedural steps and is therefore a tedious process. > o lead.

D-lysergic acid amides can also be produced from D-lysergic acid chloride hydrochloride and aliphatic Amines, e.g. B. with N-phenyl-piperazine or diethanolamine (e.g. the Swiss ■ ">"> Patent No. 4,635,525).

The invention aims at a simple process with few procedural specifications and high yield create.

The invention thus relates to a method for w> Production of lysergic acid amides by reacting D-lysergic acid chloride hydrochloride with amino alcohols in the presence of a solvent in which the reaction in the presence of DicbJoräthan as Solvent at temperatures between 17 and 24 ° C and in the presence of a hydrochloric acid binding agent, the reaction mixture is then carried out make a 5% sodium carbonate solution alkaline and extract the amide with dichloroethane

It does not matter which of the two isomers of dichloroethane, 1,2 dichloroethane or 1,1 Dichloroethane, is used.

The method of the invention has the following advantages:

A very pure substance is obtained. The manufacture of the substance is simple. The yields are approximately 88 to 92%.

example 1
D-lysergic acid propanolamide

A suspension of 1 g of D-Lysergic acid chloride hydrochloride in 100 ml of anhydrous dichloroethane (either 1.2 dichloroethane or 1.1 dichloroethane) is ^{a solution of at 0 0} C with stirring and in the presence of 1 g of potassium carbonate or 1 ml of triethylamine or pyridine 1 g of 2-aminopropanol in 30 ml of anhydrous dichloroethane is added, then stirred for 30 minutes at a temperature of 17-24 ° C., after which 50 ml of a 5% sodium carbonate solution are added. It is then extracted with dichloroethane (1.51)

The dichloroethane extract is dried over sodium sulfate and distilled to dryness For identification purposes, the residue is dissolved in methanol and then, after adding maleic acid, with Ethyl ether is precipitated as ergometrine maleate

1.2 ergometrine maleate is obtained, a solid white crystalline substance with a degree of purity of 99.9%; Melting point 167 ° C (decomposition); (») = + 50 - + 56 °, (C = 1% water); UV spectrum: maximum 312 ± 3 nm, minimum 268 ± 3 nm.

Example 2
D-lysergic acid butanolamide

A suspension of 0.5 g of D-lysergic acid chloride hydrochloride in 50 ml of anhydrous dichloroethane, cooled to 0 ° C., is stirred in the presence of 1 g Potassium carbonate or 1 ml of triethylamine or pyridine a solution of 0.5 g of 2 aminobutanol in 15 ml anhydrous dichloroethane added then stirred at 17 to 24 ° C for 30 minutes after which 25 ml of a 5% sodium carbonate solution is added and then extracted with dichloroethane (1.51) will.

The dichloroethane extract is dried over sodium sulfate and distilled to dryness.The residue obtained is dissolved in methanol for identification and then precipitated as methylergometrine maleate with ethyl ether after adding maleic acid.This gives 0.6 g of white methylergometrine maleate crystals with a purity of 99 %; Melting point 185-195 ° C (decomposition); (ex.) = +45 - + 50 °, (C = 0.5% water); UV spectrum maximum 226 ηm and 313 nm.

Claims (1)

Claim: Process for the production of D-lysergic acid amides by reacting D-lysergic acid chloride hydrochloride with amino alcohols in the presence of a solvent, characterized in that that the reaction in the presence of dichloroethane as a solvent at temperatures between 17 and 24 ° C and in the presence of a Hydrochloric acid binding agent carries out, then ι ο the reaction mixture with a 5% sodium carbonate solution makes alkaline and extracted the amide with dichloroethane