Organic Chemistry of Drug Synthesis. Volume 7

iodide in the presence of potassium carbonate. The final step involves
conversion of the carbonyl group to its sulfur equivalent. Treatment of
129b with Lawesson reagent from phosphorus sulfide (P 4 S 10 ) and
anisole, then affords the nonsteroidal progestintanaproget 130.^20

122

Br OCH

3

NH 2

O

CH 3 MgBr

123

Br OH

NH 2

CDIBr O

NH O

124

1. LDA


2. B(OCH 3 ) 3

N

OCOtBu

B(OH) 2

126

Pd(Ph 3 P) 4

O

NH O

N

BuOtCO

127

N

OCOtBu

125

O ClSO 2 NCO

NH O

N

BuOtCO

128

O NaOEt NC

NH

H

O

N

129a

NC

Lawesson

O

NH S

N

130

NC

H 3 C

O

NH O

N

129b

NC

CH 3 I

K 2 CO 3

H 3 C

B. Quinazolines

Benign prostatic hypertrophy (BPH) comprises an annoying though hardly
life-threatening condition that faces many men as they age. As the anti-
hypertensive agent prazocin came into widespread use, reports began to
accumulate of relief of BPH symptoms by patients who were taking this
a-2 sympathetic blocker These reports were later substantiated by formal
clinical trials. Detailed pharmacology then revealed thata-2 sympathetic
receptors occur in the prostate. The relief from BPH symptoms is now
attributed to the blockade of those receptors. This discovery was followed
by the introduction of compounds targeted specifically at this new indi-
cation. Thea-2 blockeralfuzocin( 139 ), shares the quinazoline moiety
with prazocin and some of its later analogues. One arm the convergent
synthesis to this agent starts with acylation of amine 131 with the ethoxy-
carbonate derivative ( 132 ) of tetrahydrofuroic acid to afford amide 133.
Hydrogenation then reduces the cyano group to the corresponding
primary amine 134. Preparation of the quinazoline moiety first involves
reaction of the dicarbonyl compound 135 with phosphorus oxychloride

178 SIX-MEMBERED HETEROCYCLES FUSED TO ONE BENZENE RING