Protocols and Methods
An alternative and robust synthesis of [13C4]Baraclude® (entecavir)
Article first published online: 16 JUL 2013
Copyright © 2013 John Wiley & Sons, Ltd.
Journal of Labelled Compounds and Radiopharmaceuticals
Volume 56, Issue 12, pages 632–636, October 2013
How to Cite
Easter, J. A., Burrell, R. C. and Bonacorsi, S. J. (2013), An alternative and robust synthesis of [13C4]Baraclude® (entecavir). J Label Compd Radiopharm, 56: 632–636. doi: 10.1002/jlcr.3064
- Issue published online: 13 NOV 2013
- Article first published online: 16 JUL 2013
- Manuscript Accepted: 24 APR 2013
- Manuscript Revised: 17 APR 2013
- Manuscript Received: 26 MAR 2013
- stable isotope labeling;
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.