Organic Chemistry of Drug Synthesis. Volume 7

function, is next replaced by benzyl with successive saponification, and then
alkylation of the resulting phenol with benzyl bromide ( 33 ). Heating 33 with
the substituted piperidine ( 34 ), exchanges the methyl group on the ester with
the primary amino group in 34 to form the corresponding amide ( 35 ).
Catalytic hydrogenation then cleaves the benzyloxy group to yield the free
phenol and thus the serotonin 5-HT receptor antagonistpiboserod( 36 ).^4

C 6 H 5 CH 2 O NH

27

Cl 3 COCl

C 6 H 5 CH 2 O NH

28

O CCl

3

C 6 H 5 CH 2 O NH

29

O OCH

3

CH 3 OH

NaOH

1. H 2
   2.Ac 2 O

CH 3 CO 2 NH

30

O OCH

3

NCS

CH 3 CO 2 NH

31

O OCH

3

Cl

CH 3 CO 2 N

32

O OCH

3

O HO Cl

1. NaOH


2. C 6 H 2 CH 2 Cl

C 6 H 5 CH 2 O
33

O OCH

3

O

NHC 4 H 9

H 2 N NHC 4 H 9

C 6 H 5 CH 2 O

35

O

O

NHC 4 H 9

HO

36

O

34 H^2 O

DABCO

DABCO = 1,4-Diazabicyclo[2,2,2]octane

N N N

HN HN

The pituitary hormone arginine vasopressin (AVP) plays a pivotal role
in regulating blood volume. Broadly speaking, excessive release of the
hormone will cause the kidneys to reabsorb water and thus increase
blood volume. The AVP antagonist would thus be useful in treating
disease marked by excessive water retention, such as congestive heart
failure. A pyrrolobenzazepine forms an important part of a non-peptide
AVP antagonists. Acylation of the known pyrrolobenzazepine ( 37 ) with

NH

N

37

+ClOC

38

N

N

Cl

Cl

NO 2 O

NR 2

39 ; R = O

40 ; R = H

N

N

Cl

O

NH

F

ClOC

F

41 O

42

1. COMPOUNDS WITH THREE FUSED RINGS 221