Efficient synthesis of 2-aryl-6-chloronicotinamides via PXPd2-catalyzed regioselective Suzuki coupling.
[reaction: see text] A short and convergent synthesis of 2-aryl-6-chloronicotinamides via regioselective Suzuki coupling of 2,6-dichloronicotinamide with aryl boronic acids is described. Regioselectivity was achieved by chelation of the palladium(0) species to an ester/amide group. The air-stable palladium catalyst PXPd2, when used in reagent-grade methanol with K(2)CO(3) as the base, afforded the best regioselectivity and shortest reaction times among the catalysts screened.
Yang
Wu
W
Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 5400, Princeton, New Jersey 08543-5400, USA. wu.yang@bms.com
Wang
Yufeng
Y
Corte
James R
JR
D001897:Boronic Acids / Q000737:chemistry; D002384:Catalysis; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D009942:Organometallic Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013237:Stereoisomerism
D001897:Boronic Acids; D009942:Organometallic Compounds; D012997:Solvents; D009536:Niacinamide; D010165:Palladium