Premium
Synthesis of the carbon‐14 labeled isotopomers of ( R )‐ N ‐methyl‐3‐[2‐methylphenoxyl]‐benzenepropanamine hydrochloride (atomoxetine hydrochloride, LY139603), and two of its metabolites
Author(s) -
Kuo Fengjiun,
Clodfelter Dean K.,
Wheeler William J.
Publication year - 2004
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.849
Subject(s) - chemistry , hydrochloride , ketone , reagent , medicinal chemistry , phenethylamine , benzoyl chloride , acetyl chloride , chloride , organic chemistry , stereochemistry , catalysis
Carbon‐14 labeled Straterra TM (Atomoxetine HCl, LY139603, (‐)‐ N ‐methyl‐3‐(2‐methylphenoxy)‐benzenepropanamine hydrochloride), a potent inhibitor of the presynaptic norepinephrine transporter, and two of its major metabolites were synthesized. The key component, S ‐(+)‐3‐chloro‐l‐phenyl‐l‐propanol‐[1‐ 14 C] was synthesized by Stille coupling of benzoyl chloride‐[carbonyl‐ 14 C] with vinyl tri ‐ n ‐butylstannane, followed by HCl addition to the vinyl ketone, and asymmetric reduction of the ketone by Corey's CBS reagent. Mitsunobu reaction of this S ‐(+)‐3‐chloro‐l‐phenyl‐l‐propanol‐[1‐ 14 C] with various phenol derivatives, followed by converting the chloride to amines, gave desired products. Copyright © 2004 John Wiley & Sons, Ltd.