Syntheses of [2-2H]-5-ethynyl-1-(β-D-ribofuranosyl) imidazole-4-carboxamide and 5-ethynyl-1-([5-3H]-β-D-ribofuranosyl)imidazole-4- carboxamide (EICAR)

Article abstract of DOI:10.1002/(SICI)1099-1344(199609)38:9<809::AID-JLCR899>3.0.CO;2-0

Metallation of 5-ethynyl-1-(2,3,5-tri-O-tert-butyldimethylsilyl-β-D-ribofura nosyl)imidazole -carboxamide (1) using n-BuLi, deuteration with deuterium oxide and removal of the tert-butyldimethylsilyl protecting groups using tetrabutylammonium fluroide yielded [2-²H]-5-ethynyl- 1-(β-D-ribofuranosyl)imidazole-4-carboxamide (5a, 75 atom % deuterium). Regiospecific deprotection of the masked aldehyde N,N'-diphenylethylenediamino synthon 14 using DIAION PK2I2 ion-exchange resin (H⁺ form) yielded the aldehyde derivative (15). Reduction of the aldehyde moiety of 15 using excess [³H]NaBH₄ gave the carbinol product 17. Removal of the ribofuranosyl 2,3-isopropylidene protecting group from 17 using 90% trifluoroacetic acid afforded 5-ethynyl-1-([5-³H]-β-D-ribofuranosyl)imidazole-4-carboxamide (18. 19% chemical yield, > 99% radiochemical purity, specific activity 1.56 Ci/mmol).