WO2010056194 5H-pyrrolo[3,4-B]pyridin derivatives and their use

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Biological target:

β-Secretase: BACE

Activity:

Inhibitor

Steps Conditions Reactions
a

i). Rieke(R) Zinc, THF, 1h

ii). CuCN(LiBr)2 1M in THF

Zincate formation
b Ti(IV) ethoxide, THF, reflux, 42h
c

i). t-BuLi, THF, -70oC, 1h

ii). HCl 2N in diethyl ether, MeOH, 4h

Cyclization
d
 		BBr3, CH2Cl2, 0oC  Hydroxyl formation (Methoxy deprotection)
e
 		Boc2O, DMAP, THF, 40oC, overnight Primary amine protection (Boc formation)
f
 		Tf2O, DIEA, CH2Cl2, overnight Hydroxyl activation (Triflate formation)
g (PdCl2(dppf).CH2Cl2), Cs2CO3, DME/EtOH/H2O 6/3/1, microwaves 150oC, 20min Suzuki cross coupling reaction and Boc deprotection