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Synthesis of carbon-14 and stable isotope labelled NN414: a potent potassium channel opener

✍ Scribed by Steen K. Johansen; Jesper B. Kristensen; Lars K. Müller; Claus U. Jessen; Christian Foged

Publisher
John Wiley and Sons
Year
2004
Tongue
French
Weight
133 KB
Volume
47
Category
Article
ISSN
0022-2135

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✦ Synopsis

Abstract

Currently, NN414, a potent β‐cell selective potassium channel opener, is undergoing clinical trials for the treatment of type 2 diabetes. Here, we report the synthesis of carbon‐14 and stable isotope labelled NN414 for use in metabolic studies and as an internal standard in pharmacokinetic assays, respectively. The carbon‐14 labelling was performed in two steps starting from an advanced intermediate. This provided [^14^C]NN414 in 60% overall radiochemical yield with a specific activity of 58mCi/mmol. The stable isotope labelling was accomplished from benzyl tert‐butyl malonate in eight steps using [^13^C,^2^H~3~]iodomethane and [^2^H~2~]dibromomethane as the source of carbon‐13/deuterium. The synthetic sequence, which included a Mannich reaction followed by deamination, a Simmons–Smith‐type cyclopropanation and a modified Curtius reaction, provided [^13^C,^2^H~5~]NN414 in 8.6% overall yield. Copyright © 2004 John Wiley & Sons, Ltd.

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