Organic Chemistry of Drug Synthesis. Volume 7

the heterocyclic part of those molecules is replaced by benzene, though the
example at hand includes a normal sugar. Thus, coupling of the benzimi-
dazole ( 156 ), with the tetracetyl ribofuranoside ( 157 ) in the presence of
N,O-bis(trimethylsylil acetamide) affords the glycosilated benzimidazole
( 158 ). Treatment on this intermediate with isopropylamine leads to displa-
cement of the bromine on the imidazole ring by isopropyl amine ( 159 ).
Saponification with aqueous sodium carbonate removes the acetyl protect-
ing groups to afford the antiviral agentmaribavir( 160 ).^22
Antidepressant drugs, whether they belong to the tricyclic or newer
SSRI series, do not as a rule become effective until2 weeks after treat-
ment has started. The recent 5HT antagonistfibanserin( 166 ), departs from
that pattern in that it starts to elevate patient’s mood within a short time
after the treatment has started. Reaction of benzimidazolone ( 161 ) with
benzoyl chloride affords the singly protected derivative 162. Alkylation
of the anion prepared from this intermediate with sodium hydride with
1,2-dichloroethane adds the linking chain for attaching the next large
moiety ( 163 ). The benzoyl group on the other imidazolone nitrogen is
then hydrolyzed in the presence of acid ( 164 ). Displacement of the term-
inal chlorine with the arylpiperazine 165 affords the alkylation product
166 and thus 166.^23

NH

HN

O

161

C 6 H 5 COCl

N

HN

O

162

O

Cl Cl

N

N

O

163

O

Cl

HCl

NH

N

O

Cl

N CF 3

CF 3

HN

NH 164

N

O

N

N

166

165

Base

B. Miscellaneous Compounds

Many new antipsychotic compounds that have been introduced over the
years that showed decreased side effect in initial trials. The promise of
such “atypical” agents often did not stand up with chronic use. The most

158 FIVE-MEMBERED HETEROCYCLES FUSED TO ONE BENZENE RING