Recent Large-Scale Applications of Transition Metal-Catalyzed Couplings for the Synthesis of Pharmaceuticals - New Trends in Cross-Coupling: Theory and Applications - page 709

Nilotinib
hydro-
chloride
mono-
hydrate

N

N

C-N bond
formation

Signal
transduction
inhibitor for
the treatment
of chronic
myeloid
leukemia

October 29,
2007

F 3 C

N
H

N

O

N

N

HCl￿H 2 O

N

Lumiracoxib Prexige C-N bond

formation

45 Novartis Cyclooxygenase-

2 selective
inhibitor
for the
treatment of
inflammation

Never
approved
in the US.
Withdrawn
from the
EU and
Australia

Not
applicable

HO 2 C

Cl

H
N

F

Imatinib
mesylate

Gleevec
Glivec

C-N bond
formation

46 Novartis Treatment of

chronic
myeloid
leukemia

May 10, 2001 January
2015

N

N

N N

N N

Me

N O ￿MsOH

Raloxifene
hydro-
chloride

Evista C-N bond

formation
(followed by
amine
displacement
by aryl
Grignard)

47 Eli Lilly Estrogen

receptor
modulator for
the treatment
of osteoporosis

December 9,
1997

March 2014

O

N

O

OH ￿HCl

S

HO

Apixaban Eliquis C-N bond

formation
(2 instances)

48 Bristol-Myers

Squibb/Pfizer

Factor Xa
inhibitor for
the prevention
of venous
thrombo-
embolic events
after hip or
knee
replacement
surgery

December
28, 2012

December
2019

O

NH 2

N

N

N

O

O

N

OMe