Hazard and Precautionary Statements (GHS)

amesergide Chemical Properties,Usage,Production

Originator

Amesergide,Onbio Inc.

Uses

Serotonin antagonist.

Manufacturing Process

To a 250 ml three-neck round bottom flask was added 10.0 g (32.01 mmol) of (8β)-1-isopropyl-6-methylergoline-8-carboxylie acid, 4.43 g (32.1 mmol) of potassium carbonate and 200 ml of N,N-dimethylformamide. The mixture was refluxed and 25 ml of a distillate was collected. The remaining solution was cooled in an ice bath, and then with an acetonitrile/carbon dioxide bath which lowered the temperature of the reaction mixture to about -45°C this mixture was added 4.59 g (33.62 mmol) of isobutyl chloroformate dropwise. The resulting mixture was stirred for approximately 5 min and 3.49 g (35.21 mmol) of cyclohexylamine was added. The reaction mixture was allowed to warm to room temperature and stirred for approximately 19 h. To the mixture was added 500 ml of ice water containing 25 ml of concentrated ammonium hydroxide. The mixture was cooled and the precipitated solid was collected by vacuum filtration. The resulting solid was washed with water and dried in vacuo to provide 10.13 g (yield 76.8%) of the (8β)-N-cyclohexyl-1-isopropyl- 6-methylergoline-8-carboxamide having a purity of 92.3%.
The resulting solid was combined with three other lots of the desired compound previously synthesized to provide a total weight of 33.6 g. This material was dissolved in 1200 ml of hot methanol and the resulting solution was filtered. The filtrate was allowed to cool to room temperature and 600 ml of water was added dropwise. The mixture was cooled in the freezer and the precipitated crystals were collected by vacuum filtration. The crystals were washed with methanol and dried in vacuo to provide 26.95 g of the desired compound having a purity of 96.5% as determined by HPLC. The dried solid was dissolved in 1100 ml of hot methanol, and the resulting solution was filtered hot and allowed to cool. To this mixture was added 600 ml of water and again the precipitated solid was collected by vacuum filtration. The solid was washed with water and dried in vacuo to provide 25.82 g of the (8β)-Ncyclohexyl- 1-isopropyl-6-methylergoline-8-carboxamide, melting point 250°C. The assayed material indicated 98.7% purity.

Therapeutic Function

Serotonin antagonist