Facile preparation of a 4-substituted [2,6-14C]pyridine: Synthesis of [14C]SK&F 105809

✍ Scribed by J. Richard Heys; A. J. Villani; A. R. Mastrocola

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: French
• Weight: 437 KB
• Volume: 38
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/(sici)1099-1344(199608)38:8<761::aid-jlcr887>3.0.co;2-2

✦ Synopsis

14ClFormaldehyde was used in a nucleophile-assisted iminium ion cyclization with N-benzyl-3-butynylamine to provide N-benzyl-4-iodo-I ,2,5,6-tetrahydr0[2,6-1~C2]pyridine. Palladium-catalyzed coupling of this vinyl iodide with the organozinc derivative 2 gave the corresponding 4arylated tetrahydropyridine. Treatment of this compound at elevated temperatures with PdlA1203 in nitrobenzene solution caused hydrogenolysis of the benzyl group and aromatization, generating the 4-substituted [2,6-14Czlpyridine 4 in good overall radiochemical yield from [{4C]formaldehyde. In high yields, compound 4 was converted via the methylsulfide [ 14C]SK&F 10556 1 (u) to the methylsulfinyl compound [I4C]SK&F 105809 (b). It is proposed that, during the iminium ion cyclization, randomization of label between the 2and 6-positions of the tetrahydropyridine ring occurs as the result of rapid equilibration between alkynyl and allenyl iminium ions, prior to cyclization.