Details

Autor(en) / Beteiligte

• Easter, John A.
• Burrell, Richard C.
• Bonacorsi Jr, Samuel J.

Titel

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

Ist Teil von

• Journal of labelled compounds & radiopharmaceuticals, 2013-10, Vol.56 (12), p.632-636

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2013

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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. This paper describes the synthesis of stable isotope‐labeled [13C4]entecavir prepared in 11 steps. A total of 239 mg of [13C4]entecavir was prepared from commercially available [13C]guanidine hydrochloride and diethyl[1,2,3‐13C3]malonate in 5.7% overall yield. 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%.