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Synthesis of three alpha 7 agonists in labeled form
Author(s) -
Elmore Charles S.,
Landvatter Scott,
Dorff Peter N.,
Powell Mark E.,
Killick David,
Blake Timothy,
Hall James,
Heys J. Richard,
Harding John,
Urbanek Rebecca,
Ernst Glen
Publication year - 2014
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3186
Subject(s) - chemistry , quinuclidine , agonist , alpha (finance) , chemical synthesis , alcohol , stereochemistry , medicinal chemistry , organic chemistry , receptor , biochemistry , in vitro , medicine , construct validity , nursing , patient satisfaction
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 C 2 ]2‐chloropyridine and subsequent coupling with spirooxirane‐2,3'‐quinuclidine. When this same coupling was attempted using [3,4,5,6‐ 2 H 4 ]2‐chloropyridine, alcohol [ 2 H 6 ]‐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 H 4 ]‐1. [ 13 C 5 ]‐2 was prepared in five steps from [ 13 C 5 ]2‐furoic acid, but the C‐14 labeled compound used [ 14 C 2 ]‐1 as the starting material instead. [ 14 C 2 ]‐3 was prepared in two steps from [carbonyl‐ 14 C]nicotinic acid.