From HTS to Market: the Discovery and Development of Maraviroc, a CCR5 Antagonist for the Treatment of HIV - Accounts in Drug Discovery Case Studies in Medicinal Chemistry - page 200

O

O N

N

Ph Ph

NH 2 Ph H N

c

H

b

a

N N

N

30 31 32 33

F

O

O

F

NH 2

O

33

Ph O NH

H O Ph

CO 2 Me N

N

R NH

i

h N

d N N

N

N N

34

R = CO 2 Me
CO 2 H
CH 2 OH
CHO

36

e
f
g

29

35

Scheme 9.1 The initial synthetic route to 29 (maraviroc). (a) H 2 NOH; then Na, pentanol, 130 1C; (b) i PrCOCl, NaHCO 3 ; (c) PCl 5 ; then
H 2 NNCOMe; then H 2 , Pd, tosic acid; (d) CbzCl; (e) NaOH, MeOH; (f) BH 3 ; (g) SO 3 .py; (h) NaBH(OAc) 3 ; (i) H 2 , Pd/C; then N-
(3-dimethylaminopropyl)-N-ethylcarbodiimide, CH 2 Cl 2 , hydroxybenztriazole, 4,4-difluorocyclohexanecarboxylic acid.