Syntheses of tritium and carbon‐14 labelled N‐ (3‐dimethyl aminopropyl) ‐N‐(ethylaminocarbonyl)‐6‐(2‐propenyl)ergoline‐8β‐carboxamide (cabergoline), a potent long lasting prolactin lowering agent

The syntheses of 3H‐ and 14C‐labelled cabergoline (FCE 21336), namely N‐(3‐dimethylaminopropyl)‐N‐(ethylamino‐carbonyl)‐6‐(2‐propenyl)ergoline‐8 β ‐carboxamide 1 and its analogues are described. Tritiated cabergoline ([3H]cabergoline) 6, namely N‐(3‐dimethylaminopropyl)‐N‐(ethylaminocarbonyl)‐6‐(2‐ [2,3‐3H]‐propenyl)ergoline‐8β‐carboxamide, was obtained, by catalytic reduction with tritium gas, according to two different synthetic procedures: ‐ a three step route, starting from 6‐(2‐propargyl)‐dihydro lysergic acid‐methyl ester 3 gave [3H]cabergoline, 97% radiochemically pure, with a specific radioactivity of 11.19 GBq/mmol and in an overall radiochemical yield of 3.5%. ‐ a one step route, starting from 1‐ethyl‐3‐(3‐dimethyl‐aminopropyl)‐3‐6′‐(2‐propargyl)ergoline‐8′β‐ carbonyflurea 5′ yielded [3H]cabergoline with a radiochemical purity >97%, specific radioactivity 1.06 TBq/mmol and radiochemical yield of 23%. A modification of this last procedure also gave [3H]dihydro cabergoline ([3H]FCE 23411), namely N‐(3‐dimethylaminopropyl) ‐N‐(ethylaminocarbonyl)‐6‐(2‐[2,3‐3H]propyl)ergoline‐8β‐carboxamide 7, 97% radiochemically pure and with a specific radioactivity up to 4.03 TBq/mmol. The synthesis of [14C]cabergoline was carried out, in a three step route, by addition of potassium[14C]cyanide to 6‐(2‐propenyl)‐8β‐chloroergoline 12 to give the expected N‐(dimethylaminopropyl)‐N‐(ethylaminocarbonyl)‐6‐(2‐propenyl)‐ergoline‐8β‐ [14C]carboxamide 15′, 97% radiochemically pure with a specific radioactivity of 2.09 GBq/mmol and an overall radiochemical yield of 16%.