Organic Chemistry of Drug Synthesis. Volume 7

N

N

O

NH 2

NH 2

116

O

+ OCH

3

OCH 3

HO 2 C

117

EDAC

EDAC = 1-ethyl-3-(3-dimethylaminopropyl) carbodimide

N

N

O

NH 2

NH

118

O OCH 3

OCH 3

O

NaOH

N

N

O H

N

O N OCH 3

OCH 3

119

CH 3 I

K 2 CO 3

N

N

O

N

O N OCH 3

OCH 3

120

CH 3

Substitution by a somewhat complex bridged biyclic moiety provides a
compound that acts as an adenosine A 1 receptor antagonist. These ubiqui-
tous receptors, which are involved in regulating oxygen consumption and
the flow of blood in cardiac tissue, generally suppress those functions. An
antagonist would thus be potentially useful for treatment of congestive
heart failure. The xanthine portion of this molecule is constructed much
as that in the previous case. Thus, acylation of the diamino pyrimidine ( 121 )
with acryloyl chloride in this case affords a single amide ( 123 ). Reaction
with base then closes the imidazole ring. Diels–Alder condensation of the
vinyl group on this ring with cyclopentadiene proceeds to form the bridged
bicyclic system ( 125 ). Oxidation of the isolated double bond on that newly
formed moiety with (MCPBA) then affords the oxirane ( 126 ). Thus the
adenosine antagonistnaxifyllineis obtained.^19

N

N

O

NH 2

NH 2

121

O

+ClOC

122

N

N

O

NH 2

O NH

O

123

NaOH N

N

O H

N

O N

124

N

N

O H

N

O N

125

MCPBA

N

N

O

HN

O N

126

O

1. COMPOUNDS WITH FIVE-MEMBERED RINGS FUSED TO SIX-MEMBERED RINGS 203