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The preparation of deuterium‐ and tritium‐labeled pirbuterol hydrochloride
Author(s) -
McIlhenny Hugh M.
Publication year - 1976
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.2580120407
Subject(s) - chemistry , tritium , deuterium , acetamide , yield (engineering) , amide , hydrochloride , hydroxymethyl , radiochemistry , nuclear chemistry , pyridine , catalysis , aqueous solution , medicinal chemistry , organic chemistry , physics , materials science , quantum mechanics , nuclear physics , metallurgy
A mild exchange labeling procedure utilizing O‐deuterated or O‐tritiated t ‐butanol with sodium catalysis afforded isotope exchange in the α‐hydrogen position of the amide N‐ t ‐butyl‐2‐(5‐benzyloxy‐6‐hydroxymethyl‐2‐pyridyl)‐2‐hydroxy‐acetamide, thereby extending the utility of this approach with ketones to poor enolizers that are base labile. Complete label retention accompanied the subsequent steps of reduction and debenzylation to 2‐hydroxymethyl‐3‐hydroxy‐6(l‐hydroxy‐2‐ t ‐butylaminoethyl)‐pyridine dihydrochloride (pirbuterol hydrochloride)‐ 2 H or ‐ 3 H, in 15‐18% overall yield at the 4 mmole level. Deuterium incorporation was estimated to be 39%; a specific activity of 206 μc/mg was achieved by radiolabeling. A radiochemical and chemical purity of > 99.5% was established. Tritium label stability was demonstrated in aqueous media at acidic, neutral and basic pH.