Synthesis of 3H- and 14C-labelled astemizole (R 43 512)

✍ Scribed by J. B. A. Thijssen; A. G. Knaeps; J. J. P. Heykants

• Publisher: John Wiley and Sons
• Year: 1983
• Tongue: French
• Weight: 257 KB
• Volume: 20
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580200711

✦ Synopsis

A s t e m i z o l e , a new a n t i h i s t a m i n e d r u g , was s p e c i f i c a l l y l a b e l l e d w i t h t r i t i u m and l 4 C a t t h r e e d i s t i n c t p o s i t i o n s . T r i t i u m w a s i n t r o d u c e d e i t h e r i n t h e 4-methoxyphenyl (11) or i n t h e 4 -f l u o r o p h e n y l m e t h y l ( I V ) m o i e t y by c a t a l y t i c d e h a l o g e n a t i o n of t h e c o r r e s p o n d i n g h a l o g e n a t e d a n a l o g u e s w i t h t r i t i u m gas, y i e l d i n g 3H-astemizole w i t h s p e c i f i c a c t i v i t i e s o f 28.7 a n d 5.0 Ci/mmol r e s p e c t i v e l y . S t a r t i n g from [ 1 4 ~1 u r e a , [ 1 4 ~1 a s t e m i z o l e was s

y n t h e s i z e d w i t h t h e l a b e l b e i n g p l a c e d i n t h e 2 -p o s i t i o n o f t h e b e n z i m i d a z o l e m o i e t y . The r a d i o a c t i v e y i e l d of t h e t h r e e -s t e p s y n t h e s

i s was 22.4 %, s p r e a d o v e r t h r e e f r a c t i o n s w i t h s p e c i f i c a c t i v i t i e s o f 4.5 m C i / m o l , 1.7 m C i / m o l a n d 0.4 mCi/mmol. The l a b e l l e d compounds were r a d i o c h e m i c a l l y p u r e a c c o r d i n g t o t h i n -l a y e r (TLC) and high-performance l i q u i d chromatography (HPLC) .