chromatography. Catalytic hydrogenation of the appropriate diastereomers leads
to scission of the benzylic carbon-to-nitrogen bond to afford the (R)-amine ( 71 )
as a single isomer. Construction of the second part of the molecule starts
by addition of sodium cyanamide to the isothiocyanate ( 72 ), itself, for example,
available from reaction of the aniline with thiophosgene. The thiourea product
( 73 ) is then condensed with the chiral amine ( 71 ) to afford 74.^13
H 3 CO CH (^3) CH 3
CH 3
67
- NH 2
CH 3
H 3 C
CH (^3) CH 3
CH 3
HN
CH 3
68
- Separate
2. H 2 H^3 C
NH 2 CH (^3) CH 3
CH 3
(^6970)
CN
N=C=S
72
NaNCN
CN
HN
73
S
NH
71
CN
CN
HN NH
HNCNCH 3
CH 3
CH 3
H 3 C
74
N
N
OH
NH 2
N NH 2
71
The activity against urinary incontinence of the adrenergic beta-3 recep-
tor agonist solabegron ( 56 ) was noted above. An agent that acts on a subset
of alpha receptors, specifically, alpha-1A/1L receptors, has also shown
activity on the same clinical end point. The synthesis starts with
Mitsonobu alkylation of the nitrophenol ( 75 ) with trityl protected imida-
zole carbinol ( 76 ) to yield the ether ( 78 ). The nitro group on the
benzene ring is then reduced by any of several methods ( 79 ). The resulting
aniline is then converted to the corresponding sulfonamide ( 80 ), by
reaction with methanesulfonyl chloride. Hydrolysis with mild acid then
removes the trityl protecting group to afforddabuzalgron( 81 ).^14
75
O 2 N
CH 3
OH
Cl
- N
HO N
C(C 6 H 5 ) 3
76
(C 6 H 5 )P
DEAD
O 2 N
CH 3
Cl
N
O N
C(C 6 H 5 ) 3
78
H 2 N
CH 3
Cl
N
O N
C(C 6 H 5 ) 3
79
SnCl2
CH 3 SO 2 Cl
HN CH^3
Cl
N
O N
C(C 6 H 5 ) 3
80
SO 2
HN CH^3 CH 3
Cl
N
O NH
81
CH (^3) SO 2 H 3 O+
52 MONOCYCLIC AROMATIC COMPOUNDS