A practical synthesis of a COX-2-specific inhibitor.
A number of synthetic strategies to the Cox-2 specific inhibitor 1 have been described. These studies have led to the identification of a novel pyridine construction using annulation of ketone 2 using a vinamidinium species 29 and ammonia in 97% assay yield. Three approaches to the synthesis of ketone 2 are described that allow for its preparation in large quantities in >65% overall yield from methyl 6-methylnicotinate.
Davies
I W
IW
Department of Process Research, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. ian_davies1@merck.com
Marcoux
J F
JF
Corley
E G
EG
Journet
M
M
Cai
D W
DW
Palucki
M
M
Wu
J
J
Larsen
R D
RD
Rossen
K
K
Pye
P J
PJ
DiMichele
L
L
Dormer
P
P
Reider
P J
PJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis*; D002851:Chromatography, High Pressure Liquid; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis*; D007527:Isoenzymes / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects*; D011725:Pyridines / Q000138:chemical synthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D011725:Pyridines; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases