Improved Methodology for the Preparation of Chiral Amines

4.1.12. Synthesis of Pamaquine:
Pamaquine is an antimalarial quinoline derivative. It is very effective against the erythrocytic
stages of all four human malarias. [8] The synthesis of pamaquine is achieved through starting
quinoline (3) which is synthesized through reaction of substituted aniline (1) with glycerol in
sulfuric acid and Nitrobenzene. The resulting nitro group is then reduced by molecular
hydrogen giving the free amine which is reductively aminated forming pamaquine
O
O
OH
OH
H 2 SO 4
HO
OH
OH
H 3 CO
NO 2
NH 2
NO 2
N
H N
H 2
NO 2
NH 2
H 3 CO
CHO
H 2 SO 4 H 3 CO
H 3 CO
1 2 3 4
Et 2 N
O
N
H 3 CO
HN
N
NEt 2
Scheme 4.12. Synthesis of Pamaquine
5
4.1.13. Synthesis of Torcetrapib:
Torcetrapib is a cholesterol lowering agent. [8] Dietary cholesterol needs be esterified in order
to be absorbed from the gut. The enzyme, cholesteryl ester transfer protein (CETP), then
completes the absorption of cholesterol. Torcetrapib inhibit this enzyme helping to lower
LDL (Low density lipoproteins) cholesterol and VLDL (Very Low Density Lipoproteins)
cholesterol. It also increases the high density–good- lipoprotein cholesterol. Preparation of
torcetrapib starts with the reaction of the trifluoromethylaniline (1) with propanal in the
presence of benzotriazole (2) which affords aminal (3). The aminal is condensed with vinyl
carbamate forming tetrahydroquinoline ring. The nitrogen group on the ring is protected as
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