Improved Methodology for the Preparation of Chiral Amines

Removal of the ethyl group on the phosphorous is done by treating with trimethylsilyl
bromide resulting in the formation of free phosphonic acid and thus perzinfotel (121).
NaCNBH 3 HN NHCO2 CH 2 C 5 H 6
H 2 N NHCO 2 CH 2 C 5 H 6
C 2 H 5 O
115
CHO
O C
P
2 H 5 O
O
P
OC 2 H 5
OC 2 H 5
116
O
O
OC 2 H 5
OC 2 H 5
117
O
OC 2 H 5
O
OC 2 H 5
O
N NHCO 2 CH 2 C 5 H 6
Pt
O
N
NH 2
C 2 H 5 O
P O
OC 2 H 5
118
C 2 H 5 O
119
P
O
OC 2 H 5
O
O
HN
N
(CH 3 ) 3 SiBr
O
O
HN
N
HO
P
O
OH
C 2 H 5 O
P
O
OC 2 H 5
121
120
Scheme 4.7.Synthesis of Perzinfote:
4.1.8. Synthesis of Namindinil:
Namindinil is used to treat hair loss in males. It has a vasodilator action improving blood
circulation in hair follicle capillaries. [7] The convergent synthesis of this drug involves
preparation of the complex alkyl group as a single enantiomer. The process involves the
preparation of imine utilizing p-toluene sulfonic acid. The imine is then reduced with borane-
THF complex yielding the secondary amine as a mixture of diastereomers. The two
diastereomers were separated by column chromatography. Hydrogenolysis of the chiral
auxiliary leads to the formation of the primary amine. The primary amine is added to thiourea
derivative forming the required compound.
88