Synthesis of three alpha 7 agonists in labeled form

Autor: Rebecca Urbanek, J. Richard Heys, Peter N. Dorff, Timothy Blake, Scott W. Landvatter, James E. Hall, Charles S. Elmore, Mark E. Powell, Glen Ernst, John R. Harding, David A. Killick
Rok vydání: 2014
Předmět:
Zdroj: Journal of Labelled Compounds and Radiopharmaceuticals. 57:342-349
ISSN: 0362-4803
Popis: In support of a program to develop an alpha 7 agonist as a treatment for Alzheimer's disease, three drug candidates, 1, 2, and 3, were prepared in labeled forms. Compound 1 was prepared in C-14 labeled form by lithiation of [2,6-(14)C2]2-chloropyridine and subsequent coupling with spirooxirane-2,3'-quinuclidine. When this same coupling was attempted using [3,4,5,6-(2)H4]2-chloropyridine, alcohol [(2)H6]-6 was the major product indicating that the primary isotope effect for the lithiation step was significant enough to shift the reaction pathway. Therefore, an alternate site of labeling was used to prepare [(2)H4]-1. [(13)C5]-2 was prepared in five steps from [(13)C5 ]2-furoic acid, but the C-14 labeled compound used [(14)C2]-1 as the starting material instead. [(14)C2]-3 was prepared in two steps from [carbonyl-(14)C]nicotinic acid.
Databáze: OpenAIRE