Organic Chemistry of Drug Synthesis. Volume 7

isoindolone ( 117 ). A second hydrogenation step reduces the nitro group to
an aniline to affordlenalidomide( 118 ).^16

D. Miscellaneous Compounds with One Heteroatom

Growth hormone has long been used for treating children whose retarded
growth was traceable to deficient levels of the polypeptide. This high mol-
ecular weight compound that was used for treating deficiencies was orig-
inally obtained from cadaver pituitary glands. Growth hormone produced
by recombinant technology became available at almost the exactly time
that it was recognized that the cadaver derived drug could potentially
carry the prions that cause fatal Creutzfelt–Jacob disease. The recombinant
derived material has as a result completely replaced the pituitary-derived
hormone. The cost of this drug, which can run as high as $170 per day
of treatment, has encouraged the search for small molecules. The dihydro-
indole ibutamoren ( 128 ), achieves much the same purpose as the

NH

N

CH 3

119

C 6 H 5 CH 2 OCOCl

N

N

CH 3

Cbz

120

Cbz = C 6 H 5 CH 2 OCO

N

HN

Cbz

121

O NHCO^2 tBu

NHCO 2 tBu

CO 2 H

122

N

N

Cbz

O

O

123

TFA

N

N

Cbz

O NH^2

O

124

N

N

Cbz

O

O

126

NH

NHCO 2 tBu

O

HO 2 C NHCO^2 tBu

EDC

NH

N

O

O

127

HN

NHCO 2 tBu

O

H 2

1. CH 2 SO 2 Cl


2. TFA N

N

O

O

HN

NH 2

O

SO 2 CH 3

128

125

1. COMPOUNDS WITH ONE HETEROATOM 153