Preparation of carbon-14 labeled N-(2-ethyl-3-chloro-4-pyridinyl)-4 -(4-chlorophenoxy)phenylacetamide

Article abstract of DOI:10.1002/(SICI)1099-1344(199802)41:2<151::AID-JLCR64>3.0.CO;2-R

A 4-step modified route has been developed for the synthesis of N-(2-ethyl-3-chloro-4-pyridinyl-2-[¹⁴C])-4-(4-chloro- phenoxy)phenylacetamide ([¹⁴C]-1). The key transformation in the sequence is an amination/cyclization pair of reactions that furnished 2-[¹⁴C]-4-amino-2-ethylpyridine (4) from 5-[¹⁴C]-1-methoxyhept-1-en-3-yn-5-one (3) and ammonia. Amine 4 was then selectively chlorinated to provide 2-[¹⁴C]-4-amino-3-chloro-2-ethylpyridine (5) which was then coupled with 4-(4-chlorophenoxy)phenylacetic ethylformic anhydride (6) in a reaction mediated by trimethylaluminum to furnish the desired, radiolabeled phenylacetamide [¹⁴C]-1.