WO2010026075 Pyridine derivatives as inhibitors of HIV-I reverse transcriptase

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Scaffold: 2-pyridone

Biological target:

HIV reverse transcriptase

Activity:

Inhibitor

Steps Conditions Reactions
a LiCl  / CuCl2 / tert-Butyl nitrite / ACN Chlorination (Sandmeyer reaction)
b

1. Trimethylsilylacetylene / trans-Dichlorobis(triphenylphosphine)palladium (II) / CuI / Et3N

2. TBAF / THF

Sonogashira reaction / Trimethylsilyl deprotection
c trans-Dichlorobis(triphenylphosphine)palldium (II) / CuI / Et3N Sonogashira reaction
Steps Conditions Reactions
a MeI / Ag2CO3 / Benzene Methoxy synthesis
b 3-chloro-5-cyanophenol / K2CO3 / DMF Ether synthesis (aromatic substitution)
c Fe / NH4Cl / H2O / EtOH Primary amine synthesis (nitro reduction)
d NBS / DMF Bromination 
e

1. Phenethylzinc bromide / Bis(tri-t-butylphosphine)palladium (0) / dioxane

2. LiBr / CuBr2 / tert-Butyl nitrite / ACN

Negishi coupling / Bromination (Sandmeyer reaction)
f Chlorotrimethylsilane / NaI / ACN Methoxy deprotection
Steps Conditions Reactions
a Pd(PPh3)4 / DMF Stille coupling
b H2 / Pd-C / MeOH Alkene reduction                  
Steps Conditions Reactions
a BnBr / Ag2CO3 / benzene O-Benzyl protection
b K2CO3 / DMF Ether synthesis (aromatic substitution) 
c Fe / NH4Cl / H2O / EtOH Primary amine synthesis (Nitro reduction)
d CuBr2 / LiBr / tBuNO2 / ACN Bromination (Sandmeyer reaction)
e Diethylzinc / (dppf)PdCl2 / dimethylaminoethanol  /THF Negishi coupling
f TFA : DCM (1:1) O-Benzyl deprotection
Steps Conditions Reactions
a NBS / ACN Bromination
b NCS /isopranol / ACN Chlorination
c NIS / AcOEt:AcOH (1:1) Iodination
Steps Conditions Reactions
a 3-Ethoxy-3-oxopropylzinc bromide / Bis(tri-t-butylphosphine)palladium (0) / dioxane Negishi coupling
b LiOH / H2O Carboxylic acid synthesis (Ester Hydrolysis)
c 2-aminophenol / polymer supported triphenylphosphine  / trichloroacetonitrile / ACN Cyclisation
Steps Conditions Reactions
a K2CO3  /DMF Ether synthesis (aromatic substitution)
b NH2-NH2 / THF Hydrazine synthesis (aromatic substitution)
c Br2 / CHCl3 Bromination
d Bis-(tri-tert-butylphosphine)palladium (0) / dioxane Negishi coupling
e NaH / THF Ether synthesis (aromatic substitution)
f TFA O-Benzyl deprotection
g NBS / ACN Bromination
Steps Conditions Reactions
a Grubb's catalyst (second generation) / DCM Metathesis 
b Pd(PPh3)4 / K2CO3 / 1,2-dimethoxyethane / H2O Suzuki reaction
c H2 / PtO2 / THF Alkene reduction
Steps Conditions Reactions
a tBuONO / aniline / diiodomethane Iodination (Sandmeyer reaction)
b Benzylzinc bromide / bis(tri-tert-butylphosphine)palladium / I2 / dioxane Negishi coupling
Steps Conditions Reactions
a Tributylallyltin / Pd(PPh3)4 / Toluene Stille coupling
b NMO / OsO4 / NaIO4 / THF / H2O Aldehyde synthesis

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