F
Br
O
O
OEt
O
+
N
H
N
Me
1. Pd 2 (dba) 3 (2 mol %)
BINAP (4 mol %)
Cs 2 CO 3 , anisole, 125 ºC
F
N
O
O
OH
O
64%
N
Me
F
N
O
O
H
N
O
N
Me
N
N
O
ZM549865
2. Aqueous KOH
3. Aqueous Acid
75
Scheme 10 Large-Scale Synthesis of ZM549865 via Pd-Catalyzed N-Arylation
N
H
Br
. HCl
1. NaOH/ toluene
2. Pd(OAc) 2 , BINAP
NaOtBu, toluene, 110 ºC
NH 3
N
N
Me
88%
N
N
Me
N
H
O
N
O
AR-A2
PhCO 2
–
+
N
H
N
Me
3. H 2 , Pd/C, H 2 O, AcOH
4. PhCO 2 H, toluene
Scheme 11 Large-Scale Synthesis of AR-A2 via Pd-Catalyzed N-Arylation
N
MOMO
Cl
+
N
H
N
CBz
Pd(OAc) 2 (2 mol % )
Et 3 N (4.4 mol %)
(±)-BINAP (2.4 mol %)
NaOt Bu, toluene, rt
95%
N
MOMO
N
N
CBz
N
O
N
N
ABT-74
N
H
N
O
HO 2 C
OH
OH
HO
Scheme 12 Large-Scale Synthesis of ABT-74 via Pd-Catalyzed N-Arylation
Palladium-Catalyzed sp
2 C–N Bond Forming Reactions. . .
41