Methanol → 1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid

Temperature

80 °C

To a solution of NaOH (0.88 g, 22 mmol) in water (20 mL) was added 3-methyl-1H-pyrazolo[3,4-b]pyridine (XIV) (0.4 g, 3 mmol). The suspension was heated at 80° C. until a clear solution was obtained. A solution of KMnO4 (1.73 g, 11 mmol) in water (180 mL) was added slowly over 2 h while heating the solution at 80° C. The solution was heated at 90° C. for an additional 2 h until the complete disappearance of starting material was observed by TLC. The solution was cooled to 70° C. and filtered through a pad of Celite. The solids were washed by boiling water. The combined filtrate was cooled to 0° C., acidified with conc. H2SO4 to pH=2 and extracted with n-butanol (2×10 mL). The n-butanol layer was concentrated under reduced pressure to get a white residue which was dissolved in DCM by adding minimum amount of MeOH and then filtered. The filtrate was concentrated to give 1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (XV) as a white solid (390 mg, 2.39 mmol, 81% yield). 1H NMR (CDCl3) δ ppm 7.37 (dd, J=8.10 Hz, J=4.52 Hz, 1H), 8.47 (dd, J=7.54 Hz, J=1.88 Hz, 1H), 8.62 (dd, J=4.52 Hz, J=1.32 Hz, 1H), 14.37 (brs, 1H).

1. customwas obtained
2. temperaturewhile heating the solution at 80° C
3. temperatureThe solution was heated at 90° C. for an additional 2 h until the complete disappearance of starting material
4. temperatureThe solution was cooled to 70° C.
5. filtrationfiltered through a pad of Celite
6. washThe solids were washed
7. temperatureThe combined filtrate was cooled to 0° C.
8. extractionextracted with n-butanol (2×10 mL)
9. concentrationThe n-butanol layer was concentrated under reduced pressure
10. customto get a white residue which
11. filtrationfiltered
12. concentrationThe filtrate was concentrated

ORD record

ord-7c52e42f5e2345009dca4d0ed21beed6

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09012472B2