Syntheses of 14 C and 3 H labelled forms of donetidine ‐ A histamine H 2 ‐antagonist

Three syntheses of radiolabelled 2‐[2‐(2‐N,N‐Dimethylaminomethyl‐5‐furanyl‐methylthio)ethylamino]‐5‐(6‐hydroxy‐4‐picolyl)‐4‐pyrimidone trihydrochloride (donetidine trihydrochloride) are described. One describes the preparation of the free base, and two of its trihydrochloride. 1 . A five stage synthesis (Scheme 1) which gave 14 C‐donetidine ( 8 ) labelled in the C 2 position of the pyrimidone ring starting from barium [ 14 C]cyanamide. The overall radiochemical yield for the synthesis was 9% to give ( 8 ) at a specific activity of 57.8mCi/mmol. 2 . A three stage synthesis (Scheme 2) which gave 14 C 2 ‐donetidine trihydrochloride ( 14 ) labelled in both methylenes of the aminoethylthio moiety starting from [1,2‐ 14 C 2 ]‐cysteamine hydrochloride. The overall radiochemical yield for the synthesis was 18% to give ( 14 ) at a specific activity of 15.4mCi/mmol. 3 . A five stage synthesis (Scheme 3) which gave 3 H‐donetidine trihydrochloride ( 22 ) labelled in the methylene of the furanlmethylthio moiety starting from sodium boro[ 3 H]‐hydride. The overall radiochemical yield for the synthesis was 1% to give ( 22 ) at a specific activity of 33.7mCi/mmo1.