Synthesis of 1‐([18O2]‐2‐nitro‐1‐imidazolyl)‐3‐methoxy‐2‐propanol ([18O2]‐misonidazole)

Abstract

AbstractA short, efficient synthesis for 1‐(2‐[18O2]‐nitro‐1‐imidazolyl)‐3‐methoxy‐2‐propanol ([18O2]‐misonidazole) from 2‐aminoimidazole is described. The required 18O‐labeled sodium nitrite (82.6 atom %) was conveiently synthesized by the treatment of sodium nitrite with DOWEX 50W (H+) in H218O. When 2‐aminoimidazole reacted with excess of 18O‐labeled sodium nitrite in the presence of sulfuric acid containing copper sulfate in H218O, the 18O‐labeled 2‐nitroimidazole was formed with a reasonable yield (43%). [18O2]‐Misonidazole (70 atom %) was achieved with good yield by the coupling of sublimed 18O‐labeled 2‐nitroimidazole with freshly distilled 1,2‐epoxy‐3‐methoxypropane in ethanol in the presence of a catalytic amount of anhydrous potassium carbonate under reflux for one hour. The desired product was purified by recrystalization and TLC, and characterized by 1H NMR and mass spectra. The 18O content and distribution of synthetic 18O‐labeled misonidazole was determined from the FAB‐MS spectra.