1H-Pyrazolo[3,4-b]pyridine-5-carboxylic acid

Uses

1H-Pyrazolo[3,4-B]pyridine-5-carboxylic acid is an important pharmaceutical intermediate used in the synthesis of various drug compounds.

Synthesis

Step 5. Ethyl 1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylate (4.4 g, 14 mmol) was dissolved in trifluoroacetic acid (TFA, 158 mL) and heated to 80 °C. The reaction mixture was stirred continuously at 80 °C for 4 hours. After completion of the reaction, the mixture was concentrated to dryness under reduced pressure. The residue was carefully poured into ice water and the pH was subsequently adjusted dropwise with 2 M aqueous sodium hydroxide (NaOH) to about 14. The precipitated solid was removed by filtration and the aqueous phase was washed with ethyl acetate. After combining the aqueous phases, the pH was adjusted to neutral (about 7) by slowly adding concentrated hydrochloric acid (HCl). The precipitate precipitated was collected by vacuum filtration and dried under vacuum to afford the target product 1H-pyrazolo[3,4-B]pyridine-5-carboxylic acid as a white solid (1 g, 80% yield). The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 14.38-13.62 (br, 1H), 9.07 (d, J = 1.6 Hz, 1H), 8.81 (d, J = 1.6 Hz, 1H), 8.32 (s, 1H). Mass spectrum (ESI+): m/z 164 [M+H]+.

References

[1] Patent: WO2013/127266, 2013, A1. Location in patent: Page/Page column 131; 133
[2] Patent: WO2013/127267, 2013, A1. Location in patent: Page/Page column 83; 84
[3] Patent: WO2013/127268, 2013, A1. Location in patent: Page/Page column 61; 62; 63
[4] Patent: WO2013/130935, 2013, A1. Location in patent: Paragraph 0182
[5] Patent: WO2013/130943, 2013, A1. Location in patent: Paragraph 0190