A novel synthesis of [2‐¹⁴C]2,5‐dichloropyrimidine

New radical methods for the potential synthesis of carbon‐13 and carbon‐14 labeled complex products

“…Products 85 and 86 were only formed in 42% and 34% yields, respectively, but also provide the possibility for the alkylation of the five position of isotopically labeled pyrimidines. 13,14 Lastly, steroid product 87 was formed in 60% yield. To make this useful for isotopic synthesis, the carbon-13 or carbon-14 would need to be located in one of the alkyl carbons of the redox-active ester or the number of equivalents of boronic acid would need to be reduced to one or to only a slight excess as was described previously for the formation of carbon-13 labeled product, 79 in Scheme 14.…”

“…Redox‐active esters were either isolated or formed in situ and then reacted with a nickel or iron catalyst and one of the eight ligands, L1–L8, shown in Figure . The majority of the reactions described in this review used ligands L1, L2, L3, or L5 . During the reaction, redox‐active esters react with the nickel or iron catalyst to eliminate carbon dioxide through electron transfer redox chemistry to generate a radical intermediate which reacts with various compounds to generate a wide range of products as shown in Scheme .…”

“…Obviously, the cyanide carbon on the aromatic ring in compound 84 would be an attractive position for isotopic labeling with carbon‐13 or carbon‐14. Products 85 and 86 were only formed in 42% and 34% yields, respectively, but also provide the possibility for the alkylation of the five position of isotopically labeled pyrimidines . Lastly, steroid product 87 was formed in 60% yield.…”

“…The majority of the reactions described in this review used ligands L1, L2, L3, or L5. [11][12][13][14][15][16][17][18] During the reaction, redox-active esters react with the nickel or iron catalyst to eliminate carbon dioxide through electron SCHEME 9 Olefin cross-coupling with carbon-13 vinyl sulfone and potential isotopically labeled daughter congeners 2 SCHEME 10 Hydrocyanation of olefins with tosyl cyanide 6 SCHEME 11 Hydrocyanation of olefins with tosyl cyanide 7 SCHEME 12 Two-step conversion of oximonitrile 53 into amidoxime, 57 7 SCHEME 13 Formation of redox-active esters and multiple radical cross-coupling reactions [11][12][13][14][15][16][17][18] FIGURE 1 Ligands L1-L8 used in redox-active ester cross-couplings SCHEME 14 Nickel catalyzed alkyl-alkyl coupling reactions between redox-active esters and alkyl zinc reagents 11 transfer redox chemistry to generate a radical intermediate which reacts with various compounds to generate a wide range of products as shown in Scheme 13.…”

An improved synthesis of [2‐14C]2, 5‐dichloropyrimidine

“…Historically, labeled pyrimidines have been difficult to prepare in high yields. Previously, our group published a five‐step synthesis of [2‐ 14 C]2, 5‐dichloropyrimidine from [ 14 C]urea by way of a boronic acid intermediate with an overall radiochemical yield of 22% . To avoid volatile and difficult to handle intermediates in that sequence and shorten the number of steps, we investigated an alternative synthesis starting from the same [ 14 C]urea precursor.…”