CS262282B1 - 13-acetyltergurid and process for preparing thereof - Google Patents

Abstract

13-acetyl terguride of formula I and method its production by hydrogenolysis of 13-acetyl-2- -bromterguride in a hydrogen atmosphere at heterogeneous palladium catalysts or platinum.

Description

The invention relates to 13-acetyl terguride of formula (I)

and a method for producing the same.

13-acetyl terguride in pharmacological tests shows significant effects on prolactin secretion.

The 13-acetylterguride of formula I has three chiral centers in the molecule, asymmetric carbons at the 5, 8 and 10 positions, with the hydrogen atom at C (5) having the beta position, the diethylureide group at C (8) having the alpha position and hydrogen at C 10) has an alpha position, thus the compound configuration is (5R, 8S, 10R).

According to the invention, 13-acetyl terguride of formula I can be prepared from 13-acetyl-2-bromo terguride of formula IX

(II) hydrogenolytic cleavage of the bromine atom bound to the 2-position by hydrogenation of a solution of 13-acetyl-2-bromo derivative under catalysis with heterogeneous palladium or platinum catalysts.

The reaction is preferably carried out by treating the substrate in a suitable protic or polar aprotic solvent such as alcohols such as methanol or ethanol, or acetic acid, optionally tetrahydrofuran, dioxane or 1,2-dimethoxyethane, and preferably in the presence of tertiary. an amine such as triethylamine, N-ethyl-N, N-diisopropylamine, 1,2,2,6,6-pentamethylpiperidine and the like, serving as acceptor by hydrogenolysis of the resulting hydrogen bromide, adds a heterogeneous palladium or platinum catalyst such as palladium or platinum black, or palladium or platinum on a suitable support, such as activated carbon or alumina, or palladium hydroxide on a suitable support, and the resulting reaction mixture is then hydrogenated under conditions dependent on the catalyst used, e.g., room temperature and hydrogen atmospheric pressure, or its slight overpressure. Alternatively, a suitable platinum or palladium compound such as tetrachloroplatinic acid or palladium chloride is added to the substrate solution in a suitable solvent as described above, and the active catalyst form is reduced in situ by hydrogen and then preferably added as an acceptor to the reaction mixture. hydrogen bromide tertiary amine, e.g. Alternatively, the hydrogenolysis can also be carried out using the above solvent and catalyst, but without the addition of a tertiary amine.

The reaction proceeds with stirring, for example at room temperature under atmospheric hydrogen pressure, depending on the catalyst used, for 1 to 20 hours and leads to high product yields,

The reaction mixture after the reaction is worked up by methods customary in the chemistry of ergoline derivatives, for example by pouring into water, optionally alkalinizing, shaking the product into a water-immiscible solvent, evaporating the solvent from solution, chromatography and / or crystallization from the solvent. a suitable solvent, e.g. ethanol.

13-Acetyl terguride is a colorless substance having a slightly basic nature and forming acid addition salts with strong acids. These water-soluble salts can be used for therapeutic purposes using a pharmaceutically acceptable acid such as hydrochloric, sulfuric, methanesulfonic, acetic, tartaric, maleic or citric acid.

The process for the preparation of 13-acetyl terguride is explained in more detail in the following non-limiting example. The melting point is determined on a Kofler block and is reported in ° C.

The structure of the substance was confirmed by infrared, ultraviolet and NMR spectra, the composition of the substance by elemental analysis.

Example

530 mg (1.15 mmol) of 13-acetyl-2-bromo-terburide are dissolved in a mixture of 10 ml of methanol and 10 ml of tetrahydrofuran and after addition of 40 mg of 20% palladium hydroxide on Norit and 0.3 ml of triethylamine the reaction mixture is stirred with hydrogen. for 4 hours. The catalyst was filtered off from the reaction mixture, washed with methanol on the filter, the combined solutions were evaporated and the residue was crystallized from ethanol. 400 mg (91% of theory) of 13-acetyl terguride are obtained,

mp 112 ° C to 114 ° C, specific rotation ^{= +} 55.34 ° (c = 0.2, pyridine)

Claims (2)

D SUBJECT OF THE INVENTION 1. 13-Acetyl terguride of formula I 2. A process for the preparation of 13-acetyl terguride of the formula I as claimed in claim 1, characterized in that 13-acetyl-2-bromo-terguride is hydrogenolysed under a hydrogen atmosphere using a heterogeneous palladium or platinum catalyst.