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The synthesis of tritium labeled cardioselectlve beta‐adrenoceptor antagonists
Author(s) -
G. Shtacher,
M. Erez,
S. Cohen,
A. Cohen,
O. Buchman
Publication year - 1977
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.2580130105
Subject(s) - chemistry , practolol , isopropylamine , tritium , phenol , acetanilide , epichlorohydrin , medicinal chemistry , glucal , ring (chemistry) , salicylaldehyde , nuclear chemistry , stereochemistry , catalysis , organic chemistry , medicine , physics , nuclear physics , propranolol , schiff base
Two cardioselective beta‐adrenoceptor antagonists: dl‐acetanalide‐4′‐[3‐(isopropylamino)‐2‐hydroxypropoxy] (“practolol”), and dl‐chloroacetanilide‐4′‐[3‐(isopropylamino) ‐2‐hydroxypropoxy] (“chloropractolol”), labeled with tritium at positions 3′ and 5′of the aromatic ring were prepared. The starting 3 materials for the synthesis of the aryloxypropanolamines was 2,6‐di‐ 3 H‐4‐acetamido phenol, prepared by catalytic dehalogenation of 2,6‐dibromo‐4‐acetamido‐phenol, employing tritium gas. Condensation of 2,6‐di‐ 3 H‐4‐acetamido‐phenol with epichlorohydrin, followed by epoxide ring opening with isopropylamine yielded 3′ 5′‐di‐ 3 H‐acetanilide‐4′‐[3‐(isopropylamino)‐2‐hydroxypropoxy], (3′,5′‐di‐ 3 H‐ practolol). Deacetylation of 3′,5′‐di‐ 3 H‐practolol followed by selective ar‐N chloroacetylation of the resulting 1‐(2′,6′‐di‐ 3 H‐4‐amino)‐phenoxy‐3‐isopropylaminopropan‐2‐ol, gave 3′,5′‐di‐ 3 H‐chloropractolol with a specific activity of 750 mCi/mmol.