Lysuride maleate, Lisuride maleate, Dopergin

稠环乙脲Chemical Name: 3-(6-Methyl-9,10-didehydroergolin-8alpha-yl)-1,1-diethylurea maleate
CAS No. 18016-80-3 (free base)
项目整合开发状态: Launched-1982
项目研究机构: Schering-Plough (Originator)
合成路线:The reaction of carboxamide (I) with lead tetraacetate and K2CO3 in DMF gives the corresponding isocyanate (II),which,without isolation is treated with diethylamine (III) to afford the target diethylurea.

合成路线:Hofmann rearrangement of isolysergic acid amide (I) using lead tetraacetate produced isocyanate (II),which was further condensed with diethylamine to furnish urea (III).Hydrogenation of N-(D-6-methyl-8-isoergolenyl)-N',N'-diethylurea (III) in the presence of Raney nickel yielded a mixture of the desired isoergoline-I-yl urea along with minor amounts of its isoergoline-II-yl epimer (IV),which were separated by column chromatography.A more stereoselective hydrogenation of (III) was achieved under Birch reduction conditions using lithium amide/aniline to deprotonate the labile urea side chain.Similarly,isolysergic acid amide (I) underwent stereoselective Birch reduction to the 9,10-dihydro derivative (V),which was converted to the title compound via lead tetraacetate-promoted Hofmann rearrangement,followed by coupling with diethylamine.