A practical synthesis of a COX-2-specific inhibitor

I W Davies; J F Marcoux; E G Corley; M Journet; D W Cai; M Palucki; J Wu; R D Larsen; K Rossen; P J Pye; L DiMichele; P Dormer; P J Reider

doi:10.1021/jo000870z

A practical synthesis of a COX-2-specific inhibitor

J Org Chem. 2000 Dec 15;65(25):8415-20. doi: 10.1021/jo000870z.

Authors

I W Davies¹, J F Marcoux, E G Corley, M Journet, D W Cai, M Palucki, J Wu, R D Larsen, K Rossen, P J Pye, L DiMichele, P Dormer, P J Reider

Affiliation

¹ Department of Process Research, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. ian_davies1@merck.com

PMID: 11112557
DOI: 10.1021/jo000870z

Abstract

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.

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
Chromatography, High Pressure Liquid
Cyclooxygenase 2
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors / chemical synthesis*
Isoenzymes / drug effects*
Magnetic Resonance Spectroscopy
Prostaglandin-Endoperoxide Synthases / drug effects*
Pyridines / chemical synthesis

Substances

Anti-Inflammatory Agents, Non-Steroidal
Cyclooxygenase 2 Inhibitors
Cyclooxygenase Inhibitors
Isoenzymes
Pyridines
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases