An alternative and robust synthesis of [(13) C4 ]Baraclude® (entecavir).


Stable isotope-labeled [(13) C4 ]entecavir (1) was prepared in 11 steps. Commercially available [(13) C]guanidine hydrochloride and diethyl[1,2,3-(13) C3 ]malonate were condensed to yield 2-amino[2,4,5,6-(13) C4 ]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 [(13) C4 ]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%.

DOI: 10.1002/jlcr.3064

Cite this paper

@article{Easter2013AnAA, title={An alternative and robust synthesis of [(13) C4 ]Baraclude® (entecavir).}, author={John Alan Easter and Richard C Burrell and Samuel J. Bonacorsi}, journal={Journal of labelled compounds & radiopharmaceuticals}, year={2013}, volume={56 12}, pages={632-6} }