The synthesis of tritium labeled cardioselectlve beta-adrenoceptor antagonists

✍ Scribed by Shtacher G.; Erez M.; Cohen S.; Cohen A.; Buchman O.

• Publisher: John Wiley and Sons
• Year: 1977
• Tongue: French
• Weight: 292 KB
• Volume: 13
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580130105

✦ Synopsis

Abstract

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.