Effects of various bases on acid-catalyzed amination of 2-chloro-5-ethylpyrimidine: synthesis of PPARpan agonist GW693085.
Bobby N Glover, Lynda A Jones, Byron S Johnson, Alan Millar, Martin H Osterhout, Shiping Xie
Index: J. Org. Chem. 75(11) , 3904-7, (2010)
Full Text: HTML
Abstract
A unique buffering effect of various bases, i-Pr(2)NEt and CaCO(3) in particular, was observed for the acid-catalyzed chloro displacement of 2-chloro-5-ethylpyrimidine with a 2-methyl-2-phenylpropanamine. The use of the carefully chosen bases was essential for the progression of the chloro displacement as well as the stability of the product in the presence of HCl formed. Research work leading to an efficient synthesis of PPARpan agonist GW693085 is described, featuring highly selective sequential N- and O-alkylations.
Related Compounds
Related Articles:
239. The Dimroth rearrangement. Part I. Some alkylated 2-iminopyrimidines. Brown DJ and Harper JS.
[J. Chem. Soc. , 1276-84, (1963)]