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

Temperature

95 °C

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.

1. temperaturethe mixture was heated
2. temperatureAfter cooling to room temperature
3. customexcess thionyl chloride was removed by evaporation under reduced pressure
4. dissolutionthe resultant solid dissolved in anhydrous acetonitrile (0.5 ml)
5. additionThis solution was added to a solution of isobutyric acid hydrazide (0.025 g) and diisopropylethylamine (0.058 ml) in anhydrous acetonitrile (1 ml)
6. stirringthe mixture stirred for a further 1.5 h
7. concentrationThe mixture was concentrated in vacuo
8. additionthe residue treated directly with phosphorus oxychloride (2 ml)
9. stirringThe resultant solution was stirred
10. temperatureheated
11. temperatureat reflux (120° C.) for 2 h
12. temperatureto cool
13. concentrationconcentrated in vacuo
14. washwas eluted sequentially with a gradient of EtOAc
15. additionFractions containing desired material
16. concentrationconcentrated in vacuo

ORD record

ord-8914ae82470a4d038d0bdb19466e7687

Source dataset

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07528148B2