反应详情

温度

65 °C

4-(2-Fluoro-4-iodophenylamino)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acid ((S)-2-hydroxypropoxy)-amide (500 mg, 0.85 mmol) was dissolved in TFA (5 mL) and the resulting mixture heated at 65° C. for 3 hours before being concentrated in vacuo. The resultant residue was dissolved in dichloromethane (10 mL) and methanol (2 mL) then stirred vigorously with aqueous saturated sodium bicarbonate solution (20 mL) for 2 hours. The aqueous layer was extracted with dichloromethane (2×10 mL) and the combined organic fractions filtered through a hydrophobic frit then concentrated in vacuo. The resultant residue was purified by reverse-phase HPLC (gradient 10-95% methanol/water+0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm) to yield the title compound as a white solid (106 mg, 27%). LCMS (Method A): RT=7.19 min, [M+H]+=472. 1H NMR (DMSO-d6, 400 MHz) 13.51 (1H, s), 10.37 (1H, s), 8.45 (1H, s), 7.80 (1H, dd, J=9.68, 1.89 Hz), 7.63-7.60 (1H, m), 7.25 (1H, t, J=8.42 Hz), 6.74 (1H, s), 3.88-3.81 (1H, m), 3.73-3.69 (2H, m), 1.05 (3H, d, J=6.34 Hz).

1. concentrationbefore being concentrated in vacuo
2. dissolutionThe resultant residue was dissolved in dichloromethane (10 mL)
3. extractionThe aqueous layer was extracted with dichloromethane (2×10 mL)
4. filtrationthe combined organic fractions filtered through a hydrophobic frit
5. concentrationthen concentrated in vacuo
6. customThe resultant residue was purified by reverse-phase HPLC (gradient 10-95% methanol/water+0.1% formic acid, Phenominex gemini PhC6, 5 micron, 250×20 mm)