Synthesis of [14C]ABT‐770, matrix metalloproteinase inhibitor (MMPI), labelled in the phenoxy ring

The MMPI ¹⁴C]ABT‐770 (1) , N‐(1S)‐1‐(4,4‐Dimethyl‐2,5‐dioxo‐1‐imi‐dazolidinyl)methyl]]‐2‐4′‐(trifluoromethoxy)1,1′‐biphenyl]‐4‐yl]oxy]ethyl]‐N‐hydroxyformamide was synthesized in 8 steps using 4‐bromophenol‐UL‐¹⁴C (10) as a starting material. The Carbon‐14 label was introduced in one of the metabolically stable biphenyl rings. The key sequence of the synthesis was a three‐step one‐pot reaction in which the hydantoin moiety was introduced, the imine oxidized and further hydrolyzed to get the penultimate precursor to ¹⁴C]ABT‐770 (1) in 56% yield. Copyright © 2003 John Wiley & Sons, Ltd.