WO2010002655 Compounds and compositions as kinase inhibitors

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Biological target:

Insulin-like growth factor: IGF-1

Analplastic lymphoma kinase: ALK

Activity:

Inhibitor

Steps Conditions Reactions
a PhNTf2, LDA, THF, -78oC Triflate formation (OH activation)
b Pd(dppf)Cl2, KOAc, DMSO, scelled tube, 80oC, 15h Boronate formation
c

i). Pd(PPh3)4, K2CO3, DMF/H2O, scelled tube 90oC, overnight

ii). H2, Pd/C, MeOH

Suzuki coupling reaction then Hydrogenation
d
Na2CO3, EtOH, 40oC, 24h SNAr
e

i). conc. aqueous HCl, 2-propanol, microwave, 130oC, 1h

ii). HCHO, MeOH, THF, AcOH, NaBH3CN

SNAr and Boc deprotection, then Reductive amination

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