Effects of various bases on acid-catalyzed amination of 2-chloro-5-ethylpyrimidine: synthesis of PPARpan agonist GW693085.
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.
Glover
Bobby N
BN
Chemical Development, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA.
Jones
Lynda A
LA
Johnson
Byron S
BS
Millar
Alan
A
Osterhout
Martin H
MH
Xie
Shiping
S
D000478:Alkylation; D000586:Amination; D002384:Catalysis; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology
C551784:GW693085; D047492:Peroxisome Proliferator-Activated Receptors; D011743:Pyrimidines