Biomedical Engineering Reference
In-Depth Information
Br
Cu-catalyzed
vinyl amidation
N
Amination
N
Cl
N
Me
N
H
2
N
N
Me
Ph
3
SiNH
2
, LiHMDS
Pd
2
(dba)
3
,
L1
PhMe, 100°C
then H
3
O
+
69%
O
CuI, Cs
2
CO
3
THF, 75°C
N
Cl
N
BOM
O
N
NHMe
O
BOM
BOM
MeHN
NHMe
85%
3
4
5
MeO
MeO
MeO
5 steps
Cu
Pd
PCy
2
i
-Pr
N
MeHN
N
Me
i
-Pr
H
O
i
-Pr
XPhos
(
L1
)
MeO
Desbromoceratamine A
SCHEME 3.4
Synthesis of desbromoceratamine A by Andersen and coworkers.
chloride. This intermediatewas eventually transformed into a hydroxymetabolite of the
antipsychotic agent aripiprazole.
The synthesis of (benzimidazolyl)piperazines and related amines with affinity
for the 5-HT
1A
receptor via Pd-catalyzed intermolecular amination of halobenzimi-
dazoles
9
was reported by L
opez-Rodr
ıguez and coworkers to be in good yields
(54-97%) (Scheme 3.6) [21].
OBn
Cl
OBn
Cl
Cl
Pd
2
(dba)
3
(
R
)-BINAP
t-
BuONa
PhMe, reflux
94%
Br
Cl
Cl
6
Cl
2 steps
N
N
N
R
O
O
NH
HN
NH
H
Aripiprazole metabolite (R = OH)
Aripiprazole (R = H)
7
8
SCHEME 3.5
Synthesis of a hydroxy metabolite of aripiprazole by Morita and coworkers.
Pd(OAc)
2
or Pd
2
(dba)
3
dppp or BINAP
t-
BuONa
PhMe, 85°C
54-97%
X
R
2
N
N
N
NHR
2
Tr
Tr
9
(Benzimidazolyl)piperazines
X = Br, I
R = aniline, piperazine, morpholine, hexylamine
SCHEME 3.6
Synthesis of
(benzimidazolyl)piperazines by Lopez-Rodr
ıguez and
coworkers.
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