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