Compounds with ergoline skeleton

#This invention relates to new compounds with ergoline skeleton and pharmaceutical compositions containing the same.

#The new compounds according to the invention correspond to the formula ##STR3## wherein R is hydrogen or methyl group,

#x y is a group of the formula ##STR4## and N IS AN INTEGER OF FROM 4 TO 10.

#2.81 g. of lysergic acid hydrazide, dissolved in 100 ml. of 0.1 N hydrochloric acid, are added to 10 ml. of a 1 N aqueous sodium nitrite solution, and thereafter 15 ml. of 1 N hydrochloric acid are added dropwise to the stirred mixture at 2.degree. to 5.degree. C. The mixture is stirred for an additional 15 minutes at 0.degree. to 5.degree. C. Thereafter the mixture is neutralized with saturated sodium bicarbonate solution, and extracted in three portions with a total amount of 2l. of ether. The etheral fractions are combined, dried over anhydrous potassium carbonate, filtered, and a solution of 1.32 g. of 3-allyloxy-2-oxy-propylamine in 100 ml. of isopropanol are added to the stirred filtrate. The mixture is stirred at room temperature for 4 hours, and thereafter washed with water. The aqueous phase is extracted with 2x50 ml. of chloroform. The organic solutions are combined, dried over anhydrous potassium carbonate, and evaporated to dryness.

#3.82 g. of lysergic acid-(3'-allyloxy-2'-oxy-propyl)-amide (free base) are dissolved in 150 ml. of acetonitrile with stirring, and a solution of 2.1 ml. of capryl chloride in 10 ml. of acetone is added dropwise to the stirred mixture at -10.degree. C. The mixture is stirred and cooled for an additional hour. The separated salt is filtered off, and the filtrate is evaporated. 100 ml. of water and 200 ml. of chloroform are added to the residue, the pH of the aqueous phase is adjusted to 8 with 10% ammonium hydroxide solution, the mixture is shaken, and the organic phase is separated. The aqueous phase is extracted five times more with 100 ml. amounts of chloroform. The organic phases are combined, dried over anhydrous sodium sulfate, and evaporated to dryness. The dry residue is dissolved in ethanol and converted into its maleate. The thus-obtained lysergic acid-(3'-allylxoy-2'-decanoyloxy-propyl)-amide bimaleate melts at 160-162.degree. C; (.alpha.).sub.D.sup.20 = +18.9.degree. (c = 0.5, in 50% ethanol). Yield: 5.2 g. (80 %).

#3.82 g. of lysergic acid-(3'-allyloxy-2'-oxy-propyl)-amide are dissolved in 150 ml. of pyridine with stirring. The solution is cooled to -20.degree. C, and a solution of 10 ml. of enanthyl chloride in 15 ml. of acetone is added dropwise. The reaction mixture is stirred at -20.degree. C for 30 minutes, then poured into 500 ml. of ice water, and 500 ml. of chloroform are added. The mixture is shaken, the organic phase is separated, and the aqueous phase is extracted with 6x50 ml. of chloroform. The organic phases are combined, dried over anhydrous sodium sulfate, filtered, and the filtrate is evaporated to dryness in vacuo. The residue is subjected to chromatography on a silica gel column (particle size of the filling agent: 0.09 to 0.16 mm.). A 90:4:30 mixture of chloroform, water and ethanol is used as eluting agent. The purified product is treated with an alcoholic solution of maleic acid. In this way 5.5 g. (85%) of lysergic acid-(3'-allyloxy-2'-enanthyloxy-propyl)-amide bimaleate are obtained: m.p.: 165.degree.-167.degree. C; (.alpha.).sub.D.sup.20 = +20.degree. (c = 0.5, in 50% ethanol).