WO2010056708 Aminotetrahydropyrans as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes

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Scaffold: tetrahydropyrane

Biological target:

Dipeptidyl peptidase-IV enzyme: DPP-4



Steps Conditions Reactions
a DIEA / DCM Ester synthesis (Esterification)
b NaH / nitromethane / DMF
c DIEA / DMF Cyclisation

1. NaBH4 / CHCl3 / isopropanol 

2. DBU / THF

3. Chiral separation

e Zinc powder / HCl 6N / EtOH  Primary amine synthesis (nitro reduction) 
f Boc2O / DCM  Boc protection
g Osmium tetroxide / tBuOH / acetone / H2O  Dihydroxyl synthesis  
h Sodium periodate / H2O / THF Ketone synthesis 
Steps Conditions Reactions
a Without solvent Alkene synthesis
b Hydrazine / EtOH Cyclisation
c NaH / ACN Sulfonamide synthesis
d TFA / DCM N-Boc deprotection
Steps Conditions Reactions
a Decaborane / MeOH Tertiary amine synthesis (reductive amination)