Yethapyrilene, I, once a commonly found a n t i h i a t u i n i c drug, has been synthesized with f o u r deuterium l a b e l s , t h r e e of which a r e on t h e thiophene ring. I n i t i a l l y , thiophene was d e u t e r a t e d by s o l r o l y s i s of t h e t e t r a m e r c u r i c acetate-derivat i r e w i t h d e u t e r i o l chloride. Carbonylation of t h e thiophene r i n g a t t h e 2-position.
by t h e a d d i t i o n of d i m e t h y l f o a u i d e t o t h e 2-1ithio-derivative,
gave [3,4,5-d,] thiophene-2oarboxaldehyde. Condensation of t h i s aldehyde with 2-uino- p y r i d i n e followed by reduction of t h e r e s u l t i n g imine with sodium borodeuteride t o y i e l d t h e N-([3,4,5-da]-2-thienyl[d]rethylene)-l-uiopyridine, VIII. s a l t of VIII with dimethylaminoethylchloride gave N,N-direthyl-N'-~2~~ridyll-N'-~C3,4,5-dal-2-thienyl-[dlmethylene~-l,2-ethane d i u i n e , I, in good y i e l d .
confirmed t h e i d e n t i t y of t h e prcduct which w i l l be u s e f u l f o r metabolic s t u d i e s .
Alkylation of t h e l i t h i u m
Combustion analY8i8, 500 d Z m, and Bm88 8pOCtrOaOt~ KEY WORDS: Yethapyrilene, deuterium l a b e l e d antihistamine8 Yethapyr i l e u e (N, N-dime thyl-N'-[2-pyr i d y l l -n'-(2-thienylme thylone)-lr2-ethanediamine) was f i r s t synthesized about 40 years ago (1). and rubrequently patented as an a n t i h i s t a m i n i c drug (2). A f t e r years of usage t h e drug was found t o be a p o t e n t r a t hepatocarcinogen (3,4), though not caroinogenio in e i t h e r guinea p i g s o r h u r t e r 8 (5) and subsequently removed from t h e m r k e t p l a o o . reported as non-oarainogenic in r a t s (6,7).