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.
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.