Organic Chemistry of Drug Synthesis. Volume 7

leave behind a hydroxyl group. Acid hydrolysis then opens the acetonide
to afford the immune system stimulant 170.^24

CO 2 CH 3

CH 3 O 2 C S

162

H 2 N

NH 2 NH HN

N

O

S

H 2 N OH

163

O

OO

tBuMe 2 SiO NH 2

POCl 3

165

N

N

Cl

H 2 N NH

O

OO

tBuMe 2 SiO

166

Si(CH 3 ) 3 Si(CH^3 )^3 N

N

Cl

S

H 2 N OH

164

Si(CH 3 ) 3

S Si(CH

3 ) 3

C 2 H 5 OCOCl

N

N

Cl

H 2 N N

O

OO

tBuMe 2 SiO

167

S Si(CH

3 ) 3

OC 2 H 5

O

Bu 3 NF

N

N

Cl

H 2 N N

O

OO

HO

168

S

O NaOCH 3 N

N

OCH 3

H 2 N N

O

OO

HO

169

S

O1. (CH 3 ) 3 SiI

2. H 3 O+

N

N

OCH 3

H 2 N N

O

HO OH

HO

170

S

O

2. COMPOUNDS WITH TWO FUSED

SIX-MEMBERED RINGS

Benzodiazepines provided the first relatively well-tolerated drugs for
treating anxiety. These drugs were a major advance over the previously
used barbiturates. A series of side effects, however, became evident over
time as the benzodiazepine gained mass usage. The most common of
these was habituation, a condition just short of true addiction. The more
recent anxiolytic compounds of the “spirone” class introduced by buspir-
one are generally free of those limitations. A compound with a markedly
different structure from these agents showed promising activity in animal
models. The pyridine dicarboxylic acid ( 171 ) is first converted to its
acid chloride with thionyl chloride; reaction with methanol then affords
the ester 172. Catalytic hydrogenation then serves to reduce the pyridine
ring to a piperidine of undefined stereochemistry ( 173 ). Reaction of 173

208 BICYCLIC FUSED HETEROCYCLES