- WO2010049731 Pyrazolo- and imidazopyridinylpyrimidineamines as IGF-1R tyrosine kinase inhibitors

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Biological target:

Insulin-like Growth Factor 1: IGF-1

Activity:

Inhibitor

Steps Conditions Reactions
a 1-(vinyloxy)butane / Pd(AcO)2 / Et3N / polyethylene glycol Heck reaction
b NBS / dioxane / H2O Cyclisation
Steps Conditions Reactions
a Ag2CO3 / tris(dibenzylidineacetone)dipalladium / PPh3/ toluene Heck reaction
Steps Conditions Reactions
a Et3N / EtOH Cyclisation
Steps Conditions Reactions
a Dimethyl sulfate / K2CO2 / Acetone Methoxy synthesis
b K2CO3 / DMSO Tertiary amine synthesis (aromatic substitution)
c H2 / Pd-C / EtOH Primary amine synthesis (nitro reduction)
Steps Conditions Reactions
a 2,2,2-trifluoroacetic anhydride / 1,4,7,10,13,16-hexaoxacyclooctadecane / tetrabutylammonium nitrate  /DCM Nitration
b H2SO4 50%  Carboxylic acid synthesis (Ester hydrolysis)
c H2 / Pd-C / MeOH Primary amine synthesis (Nitro reduction)
Steps Conditions Reactions
a Morpholine / DIEA / DMA Tertiary amine synthesis (aromatic substitution)
b H2 / PtO2 / EtOH Primary amine synthesis (Nitro reduction)
Steps Conditions Reactions
a Mopholine / Pd(AcO)2 / 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene / Cs2CO3 / dioxane Buchwald-Hartwig amination
b H2 / PtO2 / EtOH Primary amine synthesis (nitro reduction)
Steps Conditions Reactions
a Pd(PPh3)4 / K2CO3 / DME Suzuki reaction
b

1. H2 / Pd-C / EtOH

2. HCl 4N / Dioxane

Alkene reduction / N-Boc deprotection
c DBU / DCM Acylation
Steps Conditions Reactions
a Pd(PPh3)4 / K2CO3 / DME Suzuki reaction
b H2 / PtO2 / MeOH Piperidine synthesis (pyridine reduction)
c

1. Ac2O:DCM (1:1)

2. TFA:DCM (1:1)

Acylation / N-Boc deprotection
Steps Conditions Reactions
a APTS / 2-pentanol Secondary amine synthesis (nucleophilic substitution)

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