Organic Chemistry of Drug Synthesis. Volume 7

O

HO

O

10

+

F

MgBr

11

OH

O

HO

F

12

O

O

HO

F

OtBu

O

13

Br N(CH 3 ) 3

N(CH 3 ) 3 N(CH 3 ) 3

O

OH

HO

F

OtBu

O

15

1. H 3 O+


2. CH3. Et 33 NSO 2 Cl

HO

F 16

O

1. F 3 CSO 2 Cl


2. NaCN Pd(Ph
   3 P) 4 ,CuI

NC

F 17

N(CH 3 ) 3

O

14

t-BuCOCl

B. Indoles

A subclass of serotonin receptors dubbed 5-HT 4 are involved in regulation
of intestinal motility. The partial agonisttegaserod( 22 ) has proven useful
in treating conditions characterized by decreased motility, such as irritable
bowel syndrome. The drug is interestingly prescribed specifically for
use in women, since results from clinical trials indicated poor response
in men. Alkylation of thiosemicarbazone ( 18 ) with methyl iodide proceeds
on sulfur to the thioether ( 19 ). Treatment of intermediate 19 with pentyl-1-
amine leads to addition of the amine to the thioether function followed by

HN

NH 2

S

NH 2

18

CH 3 I HN

NH 2

SCH 3

NH

H 2 N HN

NH 2

NH

NH

NH

CH 3 O

CH=O

21

+

NH

CH 3 O

HN NH

NH

N

19 20

22

1. COMPOUNDS WITH ONE HETEROATOM 141