An alternative and robust synthesis of [13C4]Baraclude® (entecavir). (16th July 2013)

• Record Type: Journal Article
• Authors: Easter, John A.; Burrell, Richard C.; Bonacorsi, Samuel J.
• Is Part Of: Journal of labelled compounds & radiopharmaceuticals. Volume 56:Number 12(2013)
• Page Start: 632
• Page End: 636
• Publication Date: 2013-07-16
• Subjects: Tracers (Chemistry) -- Periodicals; Radiopharmaceuticals -- Periodicals; 615.8424
• DOI: 10.1002/jlcr.3064
• Languages: English
• ISSNs: 0362-4803

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 &gt;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], &lt;0.1%. Copyright © 2013 John Wiley &amp; Sons, Ltd.</p> </abstract>