4-Chloro-1-ethyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid → 4-Chloro-1-ethyl-5-(5-isopropyl-1,3,4-oxadiazol-2-yl)-1H-pyrazolo[3,4-b]pyridine

Participants

Reaction Conditions

Reaction Steps

Intermediate 11 (0.05 g) was dissolved in thionyl chloride (1 ml) and the mixture was heated at reflux (95° C.) with stirring for 1 h. After cooling to room temperature, excess thionyl chloride was removed by evaporation under reduced pressure and the resultant solid dissolved in anhydrous acetonitrile (0.5 ml). This solution was added to a solution of isobutyric acid hydrazide (0.025 g) and diisopropylethylamine (0.058 ml) in anhydrous acetonitrile (1 ml), and the mixture stirred for a further 1.5 h. The mixture was concentrated in vacuo and the residue treated directly with phosphorus oxychloride (2 ml). The resultant solution was stirred and heated at reflux (120° C.) for 2 h, then allowed to cool and concentrated in vacuo. The residue was applied to an SPE cartridge (silica, 5 g) which was eluted sequentially with a gradient of EtOAc:cyclohexanI (i) 1:16, (ii) 1:8, (iii) 1:4, (iv) 1:2, (v) 1:1 and (vi) 1:0. Fractions containing desired material were combined and concentrated in vacuo to afford Intermediate 13 (0.049 g). LCMS showed MH+=292; TRET=2.96 min.

Provenance & Evidence