Organic Chemistry of Drug Synthesis. Volume 7

then treated with ethyl oxalate ( 64 ) to afford the oxamic ester 65. The
carbonyl group is then reduced to the corresponding alcohol; saponification
affords the hypolipidemic agent 66.^12

I+

CH 3 O OCH 3

BF 4 –

57

+

HO

CH 3

H 3 C NO^2

58

Cu2+

CH 3 O

CH 3

H 3 C NO^2

O

F

COCl

59

60

CH 3 O

CH 3

H 3 C NO^2

O

61

O

F

HO

CH 3

H 3 C NR 2

O O

F

1. BBr 3
   2. H 2


2. NaBH 4


3. NaOH

CO 2 C 2 H 5

CO 2 C 2 H 5

HO

CH 3

H 3 C NH

O O

F

CO 2 C 2 H 5

O

65

CO 2 C 2 H 5

HO

CH 3

H 3 C NH

HO O

F

CO 2 H

O

66

6263 ; R = O; R = H

64

The few drugs currently available for treating hair loss act by very different
mechanisms, Finasteride and structurally related steroids act to diminish the
effect of testosterone, the hormone closely associated with male pattern hair
loss. The mechanism of action of the older hair growth stimulant, minoxidil
( 67 ) on the other hand, is believed to involve the compound’s vasodilatory
activity. The more recent hair growth stimulant, namindinil ( 74 ), also
shows vasodilator action. It is of note that the nitrogen-rich functionality in
the latter somewhat resembles a ring-opened version of 67. The synthesis of
the newer compound reflects the current trend to prepare drugs in chiral
form. One branch in the convergent scheme thus involves preparation of the
complex alkyl group as a single enantiomer. Thus reductive alkylation
(R)-a-methylbenzylamine ( 69 ), with pinacolone ( 68 ), gives the secondary
amine as a mixture of diastereomers. These are then separated by

3. COMPOUNDS RELATED TO ANILINE 51