title: Synthesis of novel KDR kinase inhibitors through catalytic reductive cyclization of o-nitrobenzylcarbonyl compounds.
abstract: An efficient synthesis of o-nitrobenzylcarbonyl compounds is demonstrated through the Swern-type oxidation of readily accessible phenethanol analogues. Reductive cyclization of o-nitrobenzylcarbonyl 3 using catalytic Raney nickel gives 1H-indol-2-yl-1H-quinoline 2 in 95% yield. Hydrolysis of 2 affords the KDR kinase inhibitor 1 in quantitative yield. The examination of the reductive cyclization reaction and optimization of conditions is described.
authors.affiliation: Department of Process Research, Merck & Co., Inc., P.O. Box 2000, Rahway, New Jersey 07065, USA. audrey_wong@merck.com
authors.forename: Audrey
authors.initials: A
authors.lastname: Wong
authors.forename: Jeffrey T
authors.initials: JT
authors.lastname: Kuethe
authors.forename: Ian W
authors.initials: IW
authors.lastname: Davies
authors.forename: David L
authors.initials: DL
authors.lastname: Hughes
mesh_terms: D002384:Catalysis; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D009578:Nitrobenzenes / Q000737:chemistry*; D009596:Nitrophenols / Q000138:chemical synthesis* / Q000494:pharmacology; D010084:Oxidation-Reduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D009578:Nitrobenzenes; D009596:Nitrophenols; D040301:Vascular Endothelial Growth Factor Receptor-2