Improved Methodology for the Preparation of Chiral Amines

carbonyldiimidazole (CDI) to give amide (25). The nitro group is reduced under
hydrogenation conditions using Pd-C. The resulting amine is then sulfonylated with
methanesulfonyl chloride to provide delavirdine, which is then transformed to delavirdine
H
N
Cl
N N
H
20 21
mesylate (3).
NO 2 1) CH 2 Cl 2 96%
2) (Boc) 2 O96%
BocN
O 2 N
N
N
22
1) Pd/C, H 2 ,78%
2) acetone
NaCNBH 3 91%
O 2 N
24
N
H
HN
COOH
N
HN
23
N
CDI or EDC
74%
S
H
N
HN
O O CH 3 SO 3 H
N O
H
3
N
N
N
1) H 2 , Pd/C, 66%
2) CH 3 SO 2 Cl,
pyr, CH 2 Cl 2
3) CH 3 SO 3 H
O 2 N
N
H
HN
N
O
25
N
N
Scheme 4.1. Synthesis of Delavirdine.
4.1.2. Synthesis of Muraglitazar:
Muraglitazar is developed to treat hyperglycemia and dyslipidemia through decrease
triglycerides and increase HDL cholesterol with minimal effects on LDL cholesterol. [2]
Several syntheses have been developed for its efficient preparation. Synthesis starts with the
alkylation of 4-hydroxybenzaldehyde with phenyloxazolemesylate (23), which can be easily
synthesized from commercially available alcohol (22), resulting in the aldehyde (24)
synthesis. The aldehyde is then treated with glycine methyl ester under reductive amination
conditions to provide secondary amine (25) in an excellent yield. Reaction of amine (25) with
4-methoxyphenyl chloroformate followed by hydrolysis of the methyl ester afforded
Muraglitazar in 94% yield.
82