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Keywords:

  • Baraclude®;
  • entecavir;
  • carbon-13;
  • stable isotope labeling;
  • antiviral;
  • nucleoside

Stable isotope-labeled [13C4]entecavir (1) was prepared in 11 steps. Commercially available [13C]guanidine hydrochloride and diethyl[1,2,3-13C3]malonate were condensed to yield 2-amino[2,4,5,6-13C4]pyrimidine-4,6-diol (8). This was converted to the desired purine (7) in five steps. Introduction of the chiral epoxide was followed by subsequent deprotection to give [13C4]entecavir (1), in an overall yield of 5.7% from labeled precursors. The chemical purity of the title compound was determined to be >99% by HPLC. The isotopic distribution was determined by mass spectrometry to be 282[M + 4], 98.4%; 281[M + 3], 1.6%; and 278[M + 0], <0.1%. Copyright © 2013 John Wiley & Sons, Ltd.