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Synthesis of [ 3 H] and [ 2 H 6 ]AZD6642, an inhibitor of 5‐lipoxygenase activating protein (FLAP)
Author(s) -
Lindelöf Åsa,
Ericsson Cecilia,
Simonsson Roger,
Nilsson Göran,
Grönberg Gunnar,
Elmore Charles S.
Publication year - 2016
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.3409
Subject(s) - chemistry , adduct , tritium , yield (engineering) , carbonylation , acetone , amide , stereochemistry , radiochemistry , medicinal chemistry , organic chemistry , catalysis , carbon monoxide , physics , materials science , nuclear physics , metallurgy
An AstraZeneca effort to identify a 5‐lipoxygenase activating protein inhibitor with good drug‐like properties resulted in the identification of AZD6642. To further understand its drug metabolism and pharmacokinetic properties, it was required labeled with tritium. The tritiation of AZD6642 was effected by Ir‐catalyzed exchange chemistry to give an average of one tritium per molecule. Additionally, a stable isotope labeled version of AZD6642 was required to support bioanalytical studies. The synthesis originated from [ 2 H 6 ]acetone which was converted to the trimethylsilyl cyanide adduct and subsequently reduced to give 2‐(aminomethyl)‐[1,1,1,3,3,3‐ 2 H 6 ]propan‐2‐ol in good yield. Carbonylation to give an amide adduct resulted in an intermediate that was converted to the final compound in four steps.